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1.
Environ Int ; 187: 108644, 2024 May.
Article in English | MEDLINE | ID: mdl-38636272

ABSTRACT

Glyphosate is the most widely applied herbicide worldwide. Glyphosate biomonitoring data are limited for agricultural settings. We measured urinary glyphosate concentrations and assessed exposure determinants in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study. We selected four groups of BEEA participants based on self-reported pesticide exposure: recently exposed farmers with occupational glyphosate use in the last 7 days (n = 98), farmers with high lifetime glyphosate use (>80th percentile) but no use in the last 7 days (n = 70), farming controls with minimal lifetime use (n = 100), and nonfarming controls with no occupational pesticide exposures and no recent home/garden glyphosate use (n = 100). Glyphosate was quantified in first morning void urine using ion chromatography isotope-dilution tandem mass spectrometry. We estimated associations between urinary glyphosate concentrations and potential determinants using multivariable linear regression. Glyphosate was detected (≥0.2 µg/L) in urine of most farmers with recent (91 %) and high lifetime (93 %) use, as well as farming (88 %) and nonfarming (81 %) controls; geometric mean concentrations were 0.89, 0.59, 0.46, and 0.39 µg/L (0.79, 0.51, 0.42, and 0.37 µg/g creatinine), respectively. Compared with both control groups, urinary glyphosate concentrations were significantly elevated among recently exposed farmers (P < 0.0001), particularly those who used glyphosate in the previous day [vs. nonfarming controls; geometric mean ratio (GMR) = 5.46; 95 % confidence interval (CI): 3.75, 7.93]. Concentrations among high lifetime exposed farmers were also elevated (P < 0.01 vs. nonfarming controls). Among recently exposed farmers, glyphosate concentrations were higher among those not wearing gloves when applying glyphosate (GMR = 1.91; 95 % CI: 1.17, 3.11), not wearing long-sleeved shirts when mixing/loading glyphosate (GMR = 2.00; 95 % CI: 1.04, 3.86), applying glyphosate exclusively using broadcast/boom sprayers (vs. hand sprayer only; GMR = 1.70; 95 % CI: 1.00, 2.92), and applying glyphosate to crops (vs. non-crop; GMR = 1.72; 95 % CI: 1.04, 2.84). Both farmers and nonfarmers are exposed to glyphosate, with recency of occupational glyphosate use being the strongest determinant of urinary glyphosate concentrations. Continued biomonitoring of glyphosate in various settings is warranted.


Subject(s)
Agriculture , Biological Monitoring , Biomarkers , Farmers , Glycine , Glyphosate , Herbicides , Occupational Exposure , Humans , Glycine/analogs & derivatives , Glycine/urine , Male , Occupational Exposure/analysis , Herbicides/urine , Middle Aged , Adult , Biomarkers/urine , Aged , Environmental Monitoring/methods
2.
Am J Epidemiol ; 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38400646

ABSTRACT

We synthesized the epidemiologic evidence on the associations between per- and polyfluoroalkyl substances (PFAS) exposure and breast cancer risk. Our systematic review and meta-analysis included 18 and 11 articles, respectively, covering studies up to February 2023. The summary relative risks (RR) estimated by random-effects meta-analyses did not support an association between PFAS and overall breast cancer risk (e.g., a natural log (ln)-unit increase in serum/plasma concentrations [ng/mL] for perfluorooctanoate [PFOA] RR=0.95, 95% confidence interval [CI]:0.77-1.18; perfluorooctane sulfonate [PFOS] RR=0.98, 95%CI: 0.87-1.11). However, when limiting to studies that assessed exposures prior to a breast cancer diagnosis, we observed a positive association with PFOA (a ln-unit increase, RR=1.16, 95%CI: 0.96-1.40). We also observed some possible heterogeneous associations by tumor estrogen and progesterone receptor status among postmenopausal breast cancer cases. No meaningful changes were observed after excluding the studies with high risk-of-bias (Tier 3). Based on the evaluation tool developed by the National Toxicology Program, given the heterogeneity across studies and the variability in timing of exposure measurements, the epidemiologic evidence needed to determine the association between PFAS exposure and breast cancer remains inadequate. Our findings support the need for future studies with improved study designs to determine this association.

3.
Intern Med J ; 54(2): 274-282, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37548152

ABSTRACT

BACKGROUND AND AIMS: Pulmonary rehabilitation (PR) improves dyspnoea, fatigue and healthcare-related quality of life (QoL) in patients with chronic lung disease (CLD). Non-English-speaking background (NESB) patients face language and cultural barriers that hinder their access to PR programmes, contributing to health disparities. Our trial aimed to demonstrate the effectiveness and feasibility of a Chinese language-specific PR programme on lung function, functional exercise capacity and QoL measures. METHODS: A prospective cohort study was conducted over a 2-year period. Participants were enrolled in an 8-week PR programme with biweekly sessions conducted by Chinese-speaking physiotherapists. Baseline and post-rehabilitation testing included pulmonary function testing, 6-min walk test (6MWT), St. George Respiratory Questionnaire (SGQR) and Short Form Health Survey (SF-36). RESULTS: We enrolled 76 patients (58% male) with a median age of 77 years (interquartile range (IQR) 68-81) and achieved a completion rate of 86.8% (n = 66). CLD included chronic obstructive pulmonary disease (42%), asthma (15%) and interstitial lung disease (3%). Baseline median forced expiratory volume in 1 s (FEV1) was 1.63 L (IQR 1.17-2.05), and the median 6MWT was 282 m (IQR 232-332). Post-intervention median 6MWT increased to 332 m (IQR 290-390), and the median FEV1 was 1.99 L (IQR 1.3-2.1). Both QoL measures (SGQR and SF-36) showed significant improvement after intervention (P < 0.05). CONCLUSION: Our study demonstrates that a language-specific PR programme is feasible, improving outcomes in NESB patients with CLD. The improvement in 6MWT and QoL measures was comparable to English-based programmes. Ensuring equal access to healthcare programmes, regardless of cultural background or language barriers, is crucial in promoting health equity.


Subject(s)
Language , Pulmonary Disease, Chronic Obstructive , Aged , Aged, 80 and over , Female , Humans , Male , Exercise Tolerance , Pilot Projects , Program Evaluation , Prospective Studies , Pulmonary Disease, Chronic Obstructive/rehabilitation , Quality of Life
4.
Environ Health Perspect ; 131(12): 127006, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38055050

ABSTRACT

BACKGROUND: Glyphosate is the most commonly used herbicide worldwide and has been implicated in the development of certain hematologic cancers. Although mechanistic studies in human cells and animals support the genotoxic effects of glyphosate, evidence in human populations is scarce. OBJECTIVES: We evaluated the association between lifetime occupational glyphosate use and mosaic loss of chromosome Y (mLOY) as a marker of genotoxicity among male farmers. METHODS: We analyzed blood-derived DNA from 1,606 farmers ≥50 years of age in the Biomarkers of Exposure and Effect in Agriculture study, a subcohort of the Agricultural Health Study. mLOY was detected using genotyping array intensity data in the pseudoautosomal region of the sex chromosomes. Cumulative lifetime glyphosate use was assessed using self-reported pesticide exposure histories. Using multivariable logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between glyphosate use and any detectable mLOY (overall mLOY) or mLOY affecting ≥10% of cells (expanded mLOY). RESULTS: Overall, mLOY was detected in 21.4% of farmers, and 9.8% of all farmers had expanded mLOY. Increasing total lifetime days of glyphosate use was associated with expanded mLOY [highest vs. lowest quartile; OR=1.75 (95% CI: 1.00, 3.07), ptrend=0.03] but not with overall mLOY; the associations with expanded mLOY were most apparent among older (≥70 years of age) men [OR=2.30 (95% CI: 1.13, 4.67), ptrend=0.01], never smokers [OR=2.32 (95% CI: 1.04, 5.21), ptrend=0.04], and nonobese men [OR=2.04 (95% CI: 0.99, 4.19), ptrend=0.03]. Similar patterns of associations were observed for intensity-weighted lifetime days of glyphosate use. DISCUSSION: High lifetime glyphosate use could be associated with mLOY affecting a larger fraction of cells, suggesting glyphosate could confer genotoxic or selective effects relevant for clonal expansion. As the first study to investigate this association, our findings contribute novel evidence regarding the carcinogenic potential of glyphosate and require replication in future studies. https://doi.org/10.1289/EHP12834.


Subject(s)
Chromosomes, Human, Y , Farmers , Animals , Humans , Male , Mosaicism , Agriculture , Glyphosate
5.
Environ Int ; 180: 108197, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37741007

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993-2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, ORcontinuous = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), Ptrend = 0.04; ORcontinuous = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [ORcontinuous = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations.


Subject(s)
Alkanesulfonic Acids , Caprylates , Carcinoma, Renal Cell , Environmental Pollutants , Fluorocarbons , Kidney Neoplasms , Adult , Humans , Male , Carcinoma, Renal Cell/epidemiology , Case-Control Studies , Cohort Studies , Kidney Neoplasms/epidemiology , Female
6.
Int J Cancer ; 153(4): 775-782, 2023 08 15.
Article in English | MEDLINE | ID: mdl-36843273

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are highly persistent endocrine-disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case-control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography-tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype-specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs] = 1.59 [1.01-2.50], 2.34 [1.29-4.23], and 2.19 [1.21-3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER-, PR-, ER+/PR-, and ER-/PR- tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor-positive tumors, and possibly between PFOA and receptor-negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology.


Subject(s)
Breast Neoplasms , Colorectal Neoplasms , Fluorocarbons , Ovarian Neoplasms , Male , Humans , Female , Breast Neoplasms/chemically induced , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Case-Control Studies , Prospective Studies , Prostate , Postmenopause , Early Detection of Cancer , Logistic Models , Hormones , Lung
7.
J Nutr ; 153(3): 781-797, 2023 03.
Article in English | MEDLINE | ID: mdl-36788041

ABSTRACT

BACKGROUND: Iron deficiency and overload may negatively impact women's health. There has been limited assessment of iron status and its associated factors among Canadian women. OBJECTIVES: This study investigated associations of various sociodemographic, lifestyle, medication, and dietary factors with body iron stores among pre- and postmenopausal women in Canada. METHODS: Analyses were conducted using cross-sectional, nationally representative survey and biomarker data from women aged 20-79 y (n = 6362) in the Canadian Health Measures Survey (2009-2017). Body iron stores were assessed by measuring serum concentrations of ferritin (SF). Information on potential correlates was collected during an in-home interview. Multivariable linear regression analyses were performed to evaluate associations with SF concentration, and logistic regression was used to estimate associations with iron deficiency (SF <15 µg/L) or elevated iron stores (SF >150 µg/L). RESULTS: Geometric mean SF concentrations were significantly higher in postmenopausal than in premenopausal women (73.2 versus 33.8 µg/L; P < 0.001). The prevalence of iron deficiency among pre- and postmenopausal women was 16.0% and 4.0%, respectively, whereas that of elevated iron stores was 2.7% and 21.0%, respectively. After simultaneous adjustment for multiple factors, including high-sensitivity CRP (inflammation marker), we found that age, East/Southeast Asian (versus White) race/ethnicity, alcohol, and red meat consumption were positively associated with SF concentration among pre- and postmenopausal women. In addition, aspirin use and dairy consumption were inversely associated with SF concentration among postmenopausal women only. Similar patterns were observed for associations with elevated iron stores among postmenopausal women, whereas higher grain consumption was associated with an increased prevalence of iron deficiency among premenopausal women. CONCLUSIONS: Sociodemographic, lifestyle, medication, and dietary factors are correlated with iron status determined by SF concentration among Canadian women. The findings may have implications for intervention strategies aimed at optimizing body iron stores in pre- and postmenopausal women.


Subject(s)
Anemia, Iron-Deficiency , Iron Deficiencies , Humans , Female , Iron/metabolism , Cross-Sectional Studies , Canada/epidemiology , Ferritins
8.
J Natl Cancer Inst ; 115(4): 394-404, 2023 04 11.
Article in English | MEDLINE | ID: mdl-36629488

ABSTRACT

BACKGROUND: Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study. METHODS: This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker. RESULTS: Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs lowest glyphosate quartile; geometric mean ratio = 1.15, 95% confidence interval = 1.03 to 1.28; Ptrend = .02) and MDA (geometric mean ratio = 1.20, 95% confidence interval = 1.03 to 1.40; Ptrend = .06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with statistically significantly increased 8-OHdG and MDA levels. Compared with nonfarmers, we observed elevated 8-iso-prostaglandin-F2α levels among farmers with recent, high past 12-month, or high lifetime glyphosate use. CONCLUSIONS: Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide.


Subject(s)
Herbicides , Animals , Humans , Male , 8-Hydroxy-2'-Deoxyguanosine , Herbicides/adverse effects , Oxidative Stress , Biomarkers , Agriculture , Carcinogens , Prostaglandins , Glyphosate
10.
ERJ Open Res ; 7(3)2021 Jul.
Article in English | MEDLINE | ID: mdl-34549043

ABSTRACT

BACKGROUND: Contacts of an individual with active tuberculosis (TB) disease have a higher risk of developing latent TB infection (LTBI) or active TB disease. Contact tracing is a public health measure that seeks to identify exposed contacts, screen them for co-prevalent TB and consider prophylactic treatment to prevent progression from LTBI to active TB disease. The investigators sought to determine the prevalence of LTBI and active TB disease among contacts of patients with multidrug-resistant (MDR)-TB in New South Wales, Australia. METHODOLOGY: A retrospective cohort study was performed among the contacts of patients diagnosed with MDR-TB between 2000 and 2016, inclusive, at seven chest clinics. Medical records were used to identify eligible contacts. Outcomes of screening and prophylactic treatment regimens offered to MDR-TB contacts with LTBI were characterised. Collected data included demographic information, screening tests results and initial management. RESULTS: In total, 247 contacts of 55 MDR-TB patients were identified. LTBI was identified in 105 contacts (42.5%). Preventive treatment was received by 20 contacts with LTBI (32.3%) in the form of various regimens, ranging from one to three antimicrobials, with various doses and durations. One contact with LTBI who was untreated progressed to active TB disease during the study period, according to clinic notes. CONCLUSION: Contacts of MDR-TB patients have a high prevalence of LTBI. Management of these contacts varies substantially in New South Wales, reflecting a lack of definitive evidence for preventive therapy. Further research is required to determine the optimal management of this population.

11.
Aust N Z J Public Health ; 45(5): 437-442, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34309967

ABSTRACT

OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) presents a major global health challenge. In high-income countries, treatment is individualised to optimise efficacy and reduce toxicity. We aimed to evaluate the outcomes of patients with MDR-TB receiving individualised antibiotic therapy in Australia. METHODS: This retrospective cohort study was performed in the city of Sydney in Australia and included patients diagnosed with bacteriologically confirmed MDR-TB diagnosed between 2000 and 2016. The clinical characteristics of patients and treatment details were extracted from medical records. The incidence of adverse events and end-of-treatment outcomes were also evaluated. RESULTS: Fifty-five patients with MDR-TB were identified at TB clinics in seven hospitals. The median age was 32 years (interquartile range [IQR]: 27-36 years). The median duration of the intensive phase treatment was six months (IQR 6-7 months). All patients' treatment administration was directly observed. The commonest reported adverse event was ototoxicity (44%; 23/52) and successful treatment outcomes were achieved by 95% (52/55) of patients. CONCLUSION: This study demonstrated the high treatment success rate that can be achieved using individualised treatment for MDR-TB in a well-resourced setting. Implications for public health: The expansion of individualised therapy promises to contribute to MDR-TB control and advance the ambitious goal of TB elimination by 2035.


Subject(s)
Antitubercular Agents , Tuberculosis, Multidrug-Resistant , Adult , Antitubercular Agents/adverse effects , Australia/epidemiology , Humans , New South Wales/epidemiology , Retrospective Studies , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology
12.
Cancer Causes Control ; 32(10): 1063-1083, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34120288

ABSTRACT

PURPOSE: There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged < 50 years, and factors driving this upward trend are unknown. This study investigated associations between various medical, lifestyle, and dietary factors and risk of early-onset CRC (EO-CRC). METHODS: A population-based case-control study was conducted in Ontario, Canada during 2018-2019. EO-CRC cases aged 20-49 years (n = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (n = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. RESULTS: Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47-3.84), longer sedentary time (≥ 10 vs. < 5 h/day, OR 1.93; 95% CI 1.02-3.65), greater consumption of sugary drinks (≥ 7 vs. < 1 drinks/week, OR 2.99; 95% CI 1.57-5.68), and a more Westernized dietary pattern (quartile 4 vs. 1, OR 1.92; 95% CI 1.01-3.66) were each associated with an increased risk of EO-CRC. Conversely, calcium supplement use (OR 0.53; 95% CI 0.31-0.92), history of allergy or asthma (OR 0.62; 95% CI 0.39-0.98), and greater parity in females (≥ 3 vs. nulliparity, OR 0.29; 95% CI 0.11-0.76) were each associated with a reduced risk. CONCLUSION: Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons.


Subject(s)
Colorectal Neoplasms , Case-Control Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Diet , Female , Humans , Ontario/epidemiology , Risk Factors , Young Adult
13.
Clin Infect Dis ; 72(1): 15-26, 2021 01 23.
Article in English | MEDLINE | ID: mdl-32502271

ABSTRACT

BACKGROUND: Transmission of Mycobacterium tuberculosis in healthcare settings is a preventable driver of the global tuberculosis epidemic. We aimed to assess the evidence for infection control interventions, including cough etiquette, engineering and personal respiratory protection measures, to prevent transmission of M. tuberculosis in healthcare settings. METHODS: Three independent systematic reviews were performed using 6 databases and clinical trials websites. Randomized trials, cohort studies, before-after studies, and case-control studies were included. Searches were performed for controlled studies evaluating respiratory hygiene, engineering, and personal respiratory protection measures. Outcome measures included the incidence of tuberculosis infection and disease. Studies involving transmission to either humans or animals were included. RESULTS: Evaluation of respiratory hygiene and cough etiquette interventions identified 4 human studies, with 22 855 participants, and 1 guinea pig study. Studies in humans evaluated the effects of multiple concurrent interventions. Patient use of surgical masks reduced infection by 14.8%, and tuberculosis disease was reduced by between 0.5% and 28.9%. Engineering and environmental interventions were evaluated in 10 studies of humans, including 31 776 human participants, and 2 guinea pig studies. Mechanical ventilation was associated with between 2.9% and 14% less infection. Nine studies of personal respiratory protection were included, including 33 913 participants. Infection was reduced by between 0% and 14.8% in studies where particulate respirators were used. The quality of included studies was assessed as low. CONCLUSIONS: Respiratory hygiene, engineering, and environmental infection controls and personal respiratory protection interventions were associated with reduced transmission of M. tuberculosis and reduced tuberculosis disease in healthcare settings.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Animals , Guinea Pigs , Humans , Infection Control , Infectious Disease Transmission, Patient-to-Professional , Masks , Tuberculosis/epidemiology , Tuberculosis/prevention & control
14.
Lancet Respir Med ; 8(4): 383-394, 2020 04.
Article in English | MEDLINE | ID: mdl-32192585

ABSTRACT

BACKGROUND: Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens. METHODS: We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug. FINDINGS: 58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed. INTERPRETATION: Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis. FUNDING: Canadian Institutes of Health Research, Centers for Disease Control and Prevention (USA), American Thoracic Society, European Respiratory Society, and Infectious Diseases Society of America.


Subject(s)
Antitubercular Agents/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adult , Aminosalicylic Acid/adverse effects , Canada/epidemiology , Clofazimine/adverse effects , Diarylquinolines/adverse effects , Drug-Related Side Effects and Adverse Reactions/etiology , Female , Fluoroquinolones/adverse effects , Humans , Incidence , Linezolid/adverse effects , Male , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/microbiology
15.
Health Promot Chronic Dis Prev Can ; 40(3): 70-80, 2020 Mar.
Article in English, French | MEDLINE | ID: mdl-32162509

ABSTRACT

INTRODUCTION: A majority of studies on tobacco smoke exposure and sleep quality have relied on self-reported smoking, resulting in potential exposure misclassification and biases related to self-report. The objective of this study was to investigate associations between urinary cotinine, a biological marker of tobacco smoke exposure, and sleep quality measures, including sleep duration, sleep continuity or efficiency, sleep satisfaction and alertness during normal waking hours. METHODS: Using data on a national sample of 10 806 adults (aged 18-79 years) from the Canadian Health Measures Survey (2007-2013), we performed binary logistic regression analyses to estimate associations between urinary cotinine concentrations and sleep quality measures, while controlling for potential confounders. Additionally, we performed ordinal logistic regression to assess the association between urinary cotinine concentrations and increased number of sleep problems. RESULTS: Overall, 28.7% of adult Canadian survey respondents had urinary cotinine concentrations above the limit of detection (LOD), nd the prevalence of each sleep problem ranged from 5.5% to 35.6%. Elevated urinary cotinine concentrations (quartile 4 vs.

Subject(s)
Cotinine/urine , Environmental Exposure , Sleep Hygiene/drug effects , Sleep Wake Disorders , Smoking , Tobacco Smoke Pollution , Adult , Biomarkers/urine , Canada/epidemiology , Correlation of Data , Cross-Sectional Studies , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Female , Humans , Limit of Detection , Male , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Smoking/adverse effects , Smoking/epidemiology , Smoking/urine , Tobacco Smoke Pollution/adverse effects , Tobacco Smoke Pollution/analysis
16.
Int J Cancer ; 147(5): 1354-1373, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32022258

ABSTRACT

Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case-control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER-/PR- breast cancer risk (all ptrend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR>18 vs. 0 mg/day = 0.68, 95% CI: 0.51-0.91), and dietary heme iron was associated with an increased risk, particularly the ER-/PR- subtype (ORhighest vs. lowest quintile = 1.69, 95% CI: 1.16-2.47; ptrend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (pinteraction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.


Subject(s)
Breast Neoplasms/epidemiology , Iron, Dietary/analysis , Oxidative Stress/genetics , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Case-Control Studies , Female , Humans , Menopause , Middle Aged , Odds Ratio , Ontario/epidemiology , Polymorphism, Genetic , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism
17.
Can J Public Health ; 111(2): 193-201, 2020 04.
Article in English | MEDLINE | ID: mdl-31749133

ABSTRACT

INTRODUCTION: Previous studies on traumatic brain injury trends in Canada have been restricted to hospitalization and emergency department visit data. However, many concussion patients may present first, or only, to family physicians. Therefore, the true burden of concussion in Canada is likely underestimated. The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) collects information electronically from family physicians across Canada and can potentially be used for concussion surveillance. The objective of this study is to explore the feasibility of using data collated from CPCSSN for concussion surveillance purposes and examine trends over time. METHODS: Electronic medical records housed by CPCSSN from 2010 to 2016 were analyzed. Case ascertainment was determined through a combination of International Classification of Diseases, Ninth Revision codes. Binomial regression models were used to calculate the prevalence ratio (PR) of concussion by age, sex, deprivation indices, body mass index, and comorbid conditions. RESULTS: Concussion prevalence rates increased from 2010 to 2016 (p < 0.001). Based on 2016 data, males had a higher prevalence of concussion compared with females (PR = 1.09; 95% CI 1.02, 1.18), and those aged 10-14 (PR = 8.52; 95% confidence interval [CI] 6.34, 11.44) and 15-19 (PR = 7.75; 95% CI 5.84, 10.28) had higher prevalence of concussion compared with those aged 0-4 years. CONCLUSION: This pilot study demonstrates the feasibility of using the CPCSSN system for surveillance of concussion in the Canadian population. The initial findings on prevalence are in agreement with previous studies that have used hospitalization or emergency department data.


Subject(s)
Brain Concussion/epidemiology , Electronic Health Records , Primary Health Care , Sentinel Surveillance , Adolescent , Adult , Aged , Arsenicals , Body Mass Index , Canada/epidemiology , Child , Child, Preschool , Chronic Disease/epidemiology , Female , Humans , Infant , Male , Middle Aged , Pilot Projects , Young Adult
18.
BMC Cancer ; 19(1): 543, 2019 Jun 06.
Article in English | MEDLINE | ID: mdl-31170936

ABSTRACT

BACKGROUND: Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found exclusively in animal-sourced foods, is suggested to have a more detrimental effect. Epidemiological evidence of the association between iron and breast cancer risk remains inconclusive and has not been comprehensively summarized. This systematic review and meta-analysis evaluated associations between both iron intake and body iron status and breast cancer risk. METHODS: Four electronic databases (MEDLINE, EMBASE, CINAHL, and Scopus) were searched up to December 2018 for studies assessing iron intake and/or biomarkers of iron status in relation to breast cancer risk. Using random-effects meta-analyses, pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated comparing the highest vs. lowest category of each iron measure. Dose-response meta-analyses were also performed to investigate linear and nonlinear associations. RESULTS: A total of 27 studies were included in the review, of which 23 were eligible for meta-analysis of one or more iron intake/status measures. Comparing the highest vs. lowest category, heme iron intake was significantly associated with increased breast cancer risk, with a pooled RR of 1.12 (95% CI: 1.04-1.22), whereas no associations were found for dietary (1.01, 95% CI: 0.89-1.15), supplemental (1.02, 95% CI: 0.91-1.13), or total (0.97, 95% CI: 0.82-1.14) iron intake. Associations of iron status indicators with breast cancer risk were generally in the positive direction; however, a significant pooled RR was found only for serum/plasma levels (highest vs. lowest) of iron (1.22, 95% CI: 1.01-1.47), but not for ferritin (1.13, 95% CI: 0.78-1.62), transferrin saturation (1.16, 95% CI: 0.91-1.47), or total iron-binding capacity (1.10, 95% CI: 0.97-1.25). In addition, a nonlinear dose-response was observed for heme iron intake and serum iron (both Pnonlinearity < 0.05). CONCLUSIONS: Heme iron intake and serum iron levels may be positively associated with breast cancer risk. Although associations were modest, these findings may have public health implications given the widespread consumption of (heme) iron-rich foods. In light of methodological and research gaps identified, further research is warranted to better elucidate the relationship between iron and breast cancer risk.


Subject(s)
Breast Neoplasms/pathology , Iron, Dietary , Iron/blood , Nutritional Status/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/etiology , Carcinogenesis/metabolism , Female , Ferritins/blood , Heme/chemistry , Humans , Meat/adverse effects , Middle Aged , Postmenopause , Risk , Transferrin/analysis , Young Adult
19.
Nutr Cancer ; 71(3): 385-398, 2019.
Article in English | MEDLINE | ID: mdl-30375890

ABSTRACT

Lignan intake, and its richest food source, flaxseed, have been associated with reduced breast cancer risk. Endogenous sex hormones, such as estrogens, play a role in breast cancer development, and lignans may alter these sex hormone levels. To assess the effect of flaxseed on circulating sex hormones, a randomized controlled trial was conducted among 99 postmenopausal women in Toronto, Canada. The intervention arm consumed 2 tablespoons (15 g) of ground flaxseed daily for 7 weeks; the control arm maintained usual diet. Baseline and week 7 concentrations of 14 serum sex hormones were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay, and serum enterolignans (lignan biomarker) using LC-MS/MS. Intervention effects on sex hormone levels were assessed using analysis of covariance. Serum enterolignans increased among the flaxseed arm (+516%). Women consuming flaxseed (vs. controls) had increased serum 2-hydroxyestrone [treatment effect ratio (TER) = 1.54; 95% CI: 1.18-2.00] and 2:16α-hydroxyestrone ratio (TER =1.54; 95% CI: 1.15-2.06); effects on other hormones were not statistically significant. Within the flaxseed arm, change in enterolignan level was positively correlated with changes in 2-hydroxyestrone and 2:16α-hydroxyestrone ratio, and negatively with prolactin. Findings suggest flaxseed affects certain circulating sex hormone levels with possible implications for future breast cancer prevention research.


Subject(s)
Diet , Flax , Gonadal Steroid Hormones/blood , Postmenopause/blood , Breast Neoplasms/prevention & control , Canada , Female , Flax/adverse effects , Humans , Hydroxyestrones/blood , Lignans/administration & dosage , Lignans/blood , Middle Aged , Prolactin/blood
20.
Health Promot Chronic Dis Prev Can ; 38(11): 404-418, 2018 Nov.
Article in English, French | MEDLINE | ID: mdl-30430815

ABSTRACT

INTRODUCTION: Sleep is essential for both physical and mental well-being. This study investigated sociodemographic, lifestyle/behavioural, environmental, psychosocial and health factors associated with sleep duration among Canadians at different life stages. METHODS: We analyzed nationally representative data from 12 174 Canadians aged 3-79 years in the Canadian Health Measures Survey (2009-2013). Respondents were grouped into five life stages by age in years: preschoolers (3-4), children (5-13), youth (14-17), adults (18-64) and older adults (65-79). Sleep duration was classified into three categories (recommended, short and long) according to established guidelines. Logistic regression models were used to identify life stage-specific correlates of short and long sleep. RESULTS: The proportion of Canadians getting the recommended amount of sleep decreased with age, from 81% of preschoolers to 53% of older adults. Statistically significant factors associated with short sleep included being non-White and having low household income among preschoolers; being non-White and living in a lone-parent household among children; and second-hand smoke exposure among youth. Boys with a learning disability or an attention-deficit/hyperactivity disorder and sedentary male youth had significantly higher odds of short sleep. Among adults and older adults, both chronic stress and arthritis were associated with short sleep. Conversely, mood disorder and poor/fair self-perceived general health in adults and weak sense of community belonging in adults and older men were associated with long sleep. CONCLUSION: Our population-based study identified a wide range of factors associated with short and long sleep at different life stages. This may have implications for interventions aimed at promoting healthy sleep duration.


INTRODUCTION: Le sommeil est essentiel à la fois au bien-être physique et au bien-être mental. Cette étude a examiné les facteurs sociodémographiques, comportementaux, environnementaux, psychosociaux et les facteurs de santé associés à la durée du sommeil chez les Canadiens à différentes étapes de la vie. MÉTHODOLOGIE: Nous avons analysé des données de l'Enquête canadienne sur les mesures de la santé (2009-2013), représentatives à l'échelle nationale et portant sur 12 174 Canadiens de 3 à 79 ans. En fonction de leur âge, les répondants ont été distribués en cinq groupes correspondant à cinq étapes de vie : les enfants préscolaires (3 et 4 ans), les enfants (5 à 13 ans), les adolescents (14 à 17 ans), les adultes (18 à 64 ans) et les aînés (65 à 79 ans). La durée du sommeil a été classée en trois catégories (recommandée, courte et longue) suivant les directives établies. Des modèles de régression logistique ont été utilisés pour dégager des corrélats d'une durée de sommeil courte ou longue propres à chaque étape de vie. RÉSULTATS: La proportion de Canadiens jouissant de la quantité recommandée de sommeil diminue avec l'âge, de 81 % chez les enfants préscolaires à 53 % chez les aînés. Les facteurs statistiquement significatifs associés à un sommeil court sont une ethnicité non blanche et un revenu familial faible chez les enfants préscolaires, une ethnicité non blanche et la résidence avec un seul parent chez les enfants et l'exposition à la fumée secondaire chez les adolescents. Les garçons ayant un trouble d'apprentissage ou un trouble du déficit de l'attention avec hyperactivité et les garçons adolescents sédentaires avaient des chances significativement plus élevées de connaître un sommeil court. Chez les adultes et les aînés, le stress chronique et l'arthrite ont été associés tous deux à un sommeil court. Le sommeil long a été quant à lui associé à un trouble de l'humeur et une autoperception d'une mauvaise santé générale ou passable chez les adultes et à un faible sens d'appartenance communautaire chez les adultes ainsi que chez les aînés de sexe masculin. CONCLUSION: Notre étude de population a dégagé une grande variété de facteurs associés à un sommeil court ou long à différentes étapes de la vie, ce qui pourrait jouer un rôle dans l'élaboration des interventions visant à promouvoir une durée de sommeil saine.


Subject(s)
Sleep , Adolescent , Adult , Age Factors , Aged , Canada , Child , Child, Preschool , Female , Health Status , Health Surveys , Humans , Life Style , Logistic Models , Male , Mental Health , Middle Aged , Socioeconomic Factors , Time Factors , Young Adult
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