Accuracy of self-reported diagnoses of polymyalgia rheumatica and giant cell arteritis in the French prospective E3N- EPIC cohort: A validation study.

OBJECTIVES: To assess the accuracy of self-reported giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) diagnoses in a large French population-based prospective cohort, and to devise algorithms to improve their accuracy. METHODS: The E3N-EPIC cohort study (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale) includes 98,995 French women born between 1925 and 1950, recruited in 1990 to study risk factors of cancer and chronic diseases. They completed biennially mailed questionnaires to update their health-related information and lifestyle characteristics. In three questionnaires, women could self-report a diagnosis of GCA/PMR. Those women were additionally sent a specific questionnaire, designed to ascertain self-reported diagnoses of GCA/PMR. Four algorithms were then devised to improve their identification. Accuracies of self-reported diagnoses and of each algorithm were calculated by comparing the diagnoses with a blinded medical chart review. RESULTS: Among 98,995 participants, 1,392 women self-reported GCA/PMR. 830 women sent back the specific questionnaire, and 202 women provided medical charts. After independent review of the 202 medical charts, 87.6 % of the self-reported diagnoses of GCA/PMR were accurate. Using additional data from a specific questionnaire (diagnosis confirmation by a physician, and self-report of >3-month of glucocorticoids), and from a reimbursement database (at least two deliveries of glucocorticoids in less than 3 consecutive months) improved their accuracy (91.8 % to 92.8 %). CONCLUSION: The accuracy of self-reported diagnosis of GCA/PMR was high in the E3N-cohort but using additional data as a specific GCA/PMR questionnaire and/or corticosteroid reimbursement database further improved this accuracy. With nearly 600 detected cases of GCA/PMR, we will be able to investigate risk factors for GCA/PMR in women.

Risk Prediction Models for Cardiotoxicity of Chemotherapy Among Patients With Breast Cancer: A Systematic Review.

Importance: Cardiotoxicity is a serious adverse effect that can occur in women undergoing treatment for breast cancer. Identifying patients who will develop cardiotoxicity remains challenging. Objective: To identify, describe, and evaluate all prognostic models developed to predict cardiotoxicity following treatment in women with breast cancer. Evidence Review: This systematic review searched the Medline, Embase, and Cochrane databases up to September 22, 2021, to include studies developing or validating a prediction model for cardiotoxicity in women with breast cancer. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess both the risk of bias and the applicability of the prediction modeling studies. Transparency reporting was assessed with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) tool. Findings: After screening 590 publications, we identified 7 prognostic model studies for this review. Six were model development studies and 1 was an external validation study. Outcomes included occurrence of cardiac dysfunction (echocardiographic parameters), heart failure, and composite clinical outcomes. Model discrimination, measured by the area under receiver operating curves or C statistic, ranged from 0.70 (95% IC, 0.62-0.77) to 0.87 (95% IC, 0.77-0.96). The most common predictors identified in final prediction models included age, baseline left ventricular ejection fraction, hypertension, and diabetes. Four of the developed models were deemed to be at high risk of bias due to analysis concerns, particularly for sample size, handling of missing data, and not presenting appropriate performance statistics. None of the included studies examined the clinical utility of the developed model. All studies met more than 80% of the items in TRIPOD checklist. Conclusions and Relevance: In this systematic review of the 6 predictive models identified, only 1 had undergone external validation. Most of the studies were assessed as being at high overall risk of bias. Application of the reporting guidelines may help future research and improve the reproducibility and applicability of prediction models for cardiotoxicity following breast cancer treatment.

A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.

BACKGROUND: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. OBJECTIVE: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. METHODS: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. RESULTS: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. CONCLUSIONS: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Menopausal hormone therapy and risk of incident hypertension: role of the route of estrogen administration and progestogens in the E3N cohort.

OBJECTIVES: Although menopausal hormone therapy (MHT) remains the most effective treatment for vasomotor symptoms of menopause, its association with the development of arterial hypertension remains unclear. We sought to explore associations between different formulations of MHT and incident hypertension among menopausal women in a prospective cohort study. METHODS: We used the Etude Epidémiologique de femmes de la Mutuelle Générale de l'Education (E3N) cohort, a French prospective population-based study initiated in 1990 on 98,995 women. Out of these, 49,905 menopausal women with complete information on the use of MHT, and without prevalent hypertension at inclusion were included. RESULTS: The mean age of the population at baseline was 54.2 ±â€Š4.3 years, and 32,183 (64.5%) reported ever using MHT. Among these women, 10,173 cases of incident hypertension were identified over an average follow-up time of 10.6 years. Compared with women who never used MHT, those who ever used it had an increased risk of incident hypertension (adjusted HR 1.07, 95% CI 1.02-1.12) after adjustment for body mass index and other potential confounders. Oral but not transdermal estrogen use was associated with an increased risk of hypertension (adjusted HR = 1.09; 95% CI: 1.04-1.14 and HR = 1.03; 95% CI: 0.99-1.07, respectively). However, the HRs associated with oral and transdermal estrogens did not differ significantly (P-homogeneity = 0.09). Regarding the role of concomitant progestogens, pregnane and norpregnane derivatives were significantly associated with hypertension risk (HR = 1.12; 95% CI: 1.06-1.19 and HR = 1.06; 95% CI: 1.01-1.13, respectively). CONCLUSIONS: MHT was associated with a modest but significant increased risk of incident hypertension, especially when using oral estrogen in combination with a progestogen such as pregnane and norpregnane derivatives. Surveillance of blood pressure should be added to the medical surveillance of MHT users.

Video Summary:http://links.lww.com/MENO/A802 .

Hysterectomy, non-malignant gynecological diseases, and the risk of incident hypertension: The E3N prospective cohort.

OBJECTIVES: While it has been reported that women with uterine fibroids or endometriosis are commonly overweight and hypertensive, the association between non-malignant gynecological diseases and the risk of hypertension has been little studied prospectively. The aim of this study was to investigate in a large French cohort of women whether a history of hysterectomy, uterine fibroids, or endometriosis was prospectively related to an increased risk of incident hypertension. STUDY DESIGN: We analyzed 50,286 women from the E3N cohort who were free of hypertension at baseline, with a median follow-up of 16.4 years. MAIN OUTCOME MEASURES: Gynecological diseases were based on self-report. Cox proportional hazards models with age as the timescale were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Covariates included smoking status, body mass index (BMI), physical activity, and hormonal factors. RESULTS: A total of 12,073 women (24%) developed hypertension during follow-up. Women with a history of hysterectomy had an increased risk of incident hypertension, which persisted after adjustment for potential confounding factors (adjusted HR=1.18, 95% CI 1.12-1.24). Risk was similar in women with hysterectomy with or without oophorectomy. Risk of hypertension was higher in women with a history of endometriosis (HRendometriosis 1.19, 95%CI 1.11-1.22) or uterine fibroids (HRfibroids 1.18, 95%CI 1.13-1.22), irrespective of hysterectomy. Associations were similar after further adjustment for BMI. CONCLUSIONS: Hysterectomy and non-malignant gynecological diseases were associated with an increased risk of hypertension in this large prospective study. Women with these conditions may benefit from blood pressure monitoring. ClinicalTrials.gov identifier: NCT03285230.

The associations of the Palaeolithic diet alone and in combination with lifestyle factors with type 2 diabetes and hypertension risks in women in the E3N prospective cohort.

PURPOSE: Patterns of change from the traditional Palaeolithic lifestyle to the modern lifestyle may partly explain the epidemic proportions of non-communicable diseases (NCDs). We investigated to what extent adherence to the Palaeolithic diet (PD) and the Palaeolithic-like lifestyle was associated with type 2 diabetes (T2D) and hypertension risks. METHODS: A study of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort, followed up for nearly 20 years. There were 3292 incident T2D and 12,504 incident hypertension cases that were validated. Dietary data were collected at baseline in 1993 via a food frequency questionnaire. The PD score and the Palaeolithic-like lifestyle score (PD, physical activity, smoking status, and body mass index [BMI]) were derived and considered in quintiles. Multivariable Cox regression models were employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident T2D and hypertension. RESULTS: In the fully adjusted models, a 1-SD increase of the PD score was associated with 4% and 3% lower risks of T2D and hypertension, respectively. Those in the highest versus the lowest quintile of the score had HR (95% CI) of 0.88 (0.79, 0.98) and 0.91 (0.86, 0.96) for T2D and hypertension, respectively (P-trend < 0.0001). Associations were stronger for the Palaeolithic-like lifestyle score; in the fully adjusted model, a 1-SD increase of the score was associated with 19% and 6% lower risks of T2D and hypertension, respectively. Risks lowered successively with each increase in quintile; those in the highest versus the lowest quintile had HR (95% CI) of 0.58 (0.52, 0.65) and 0.85 (0.80, 0.90) for T2D and hypertension, respectively (P-trend < 0.0001). CONCLUSIONS: Our data suggest that adhering to a PD based on fruit, vegetables, lean meats, fish, and nuts, and incorporating a Palaeolithic-like lifestyle could be promising options to prevent T2D and hypertension.

Physical activity and stroke among women - A non-linear relationship.

Studies have identified non-linear inverse relationships between physical activity and the risk of stroke. A U-shaped response has been observed between haemorrhagic stroke and physical activity. The objective of this study was to investigate the associations between physical activities on stroke. We used data from the E3N cohort study, a French prospective study of women initiated in 1990. From the women in the study, we included those without cardiovascular disease or cancer at baseline, resulting in 94,169 women. We assessed total physical activity in 1993, grouped as quartiles. Cox models adjusted for potential confounders were used to assess the relationship with stroke, considering cases until 2008. Splines were used to assess the shape of the response. Similarly, we then considered high and low-intensity physical activity grouped as tertiles. Among the included women, with a mean age of 51.2 ± 6.7 years, 592 cases of stroke were identified over an average follow-up time of 16.2 years. Total physical activity was associated with a lower stroke risk (HRQ1-Q4 = 0.38 [0.31, 0.49]). An inverse relationship was observed between physical activity and all stroke sub-types. A non-linear (L-shaped) relationship was observed for all-stroke, and ischemic stroke, and a U-shaped response for sub-arachnoid and intracerebral haemorrhage. High-intensity activities were associated with a U-shaped response for haemorrhagic stroke types. Low-intensity activities were associated with a linear response for all stroke types. Our results support other observations that physical activity may reduce stroke risk.

A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort.

Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m2) or obese (BMI ≥ 30 kg/m2) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.

High dietary total antioxidant capacity is associated with a reduced risk of hypertension in French women.

BACKGROUND: Although there is evidence for a reduced risk of hypertension associated with fruit and vegetable consumption, the relationship between the total antioxidant capacity of the diet (TAC) and the risk of hypertension has not been previously examined. We aimed to evaluate that association in the large E3N French prospective cohort of women. METHODS: Dietary TAC was estimated using total radical-trapping ability parameter (TRAP) assay food values; self-reported incident hypertension cases were validated. Cox regression models were adjusted for conventional risk factors, body mass index, physical activity, energy, sodium, magnesium, omega-3 fatty acids, and alcohol. RESULTS: After an average 12.7 years of follow up, there were 9350 incident cases of hypertension among 40,576 women. Dietary TAC was inversely associated with the risk of hypertension with a 15% lower risk of hypertension in those in the fifth vs. first quintile (HRQ5 0.85 [CI 95% 0.74; 0.95] p-trend 0.03) An inverse dose-effect relationship was observed for dietary TAC excluding coffee (HRQ5 0.85 [CI 95% 0.74; 0.95], p-trend 0.0008), while for dietary TAC from coffee, only the highest quintile was inversely associated with risk (HRQ5 0.86 [0.75, 0.97], p-trend 0.20). In a fully partitioned model with major dietary TAC contributors, TAC from fruit/vegetables, wine, and miscellaneous sources was inversely associated with risk, while associations with TAC from coffee, tea, and chocolate were not statistically significant. CONCLUSIONS: In a large prospective cohort, the risk of incident hypertension in women was inversely associated with the antioxidant capacity of the diet, suggesting that promoting a diet naturally rich in antioxidants might help prevent the development of hypertension.

Non-contrast MRI methods as a tool for the pre-operative assessment and surveillance of the arterio-venous fistula for haemodialysis.

OBJECTIVE: To compare non-contrast enhanced MRI with ultrasound (US) for measurement of arm blood vessel geometries and flow velocities in volunteers and patients with end-stage renal disease. MATERIALS AND METHODS: Subjects were scanned using US (reference standard), and MRI 2D time-of-flight (ToF), 2D phase contrast (PC), and 3D multi-echo data image combination (MEDIC). Patients were also scanned after arteriovenous fistula (AVF) surgery. RESULTS: For mean vessel diameters (radial and brachial arteries; cephalic vein) MEDIC measurements were similar to US (p > 0.05). However, ToF underestimated the mean diameter of the cephalic vein relative to US (p < 0.05). For arterial velocity measurements, the mean values derived by PC-MR and US were similar (p > 0.05). Post-operatively, the intra-luminal signal intensity was hypo-intense at the anastomosis site using ToF and MEDIC. At the same site the outer boundary of the vessel was consistently lost on ToF, but remained clearly delineated on the MEDIC images. DISCUSSION: With the exception of ToF, the MRI data demonstrated excellent agreement with US for measurements of vessel geometry and flow velocity. Further, the ability to clearly delineate the post-surgery vessel edges with MEDIC MRI suggests that the technique may be useful for surveillance after AVF creation or for patient-specific modelling studies.

Introduction of a compressed air breathing apparatus for the offshore oil and gas industry.

INTRODUCTION: When a helicopter ditches the majority of crew and passengers have to make an underwater escape. Some may not be able to hold their breath and will drown. For at least 15 yr, military aircrew have been trained to use a scuba system. In the offshore oil and gas industry, there has been more caution about introducing a compressed air system and a rebreather system has been introduced as an alternative. Recently, Canadian industry and authorities approved the introduction of Helicopter Underwater Emergency Breathing Apparatus (HUEBA) training using compressed air. This communication reports the training of the first 1000 personnel. METHODS: Training was introduced in both Nova Scotia and Newfoundland concurrently by the same group of instructors. Trainees filled out a questionnaire concerning their perceived ratings of the ease or difficulty of classroom training and the practical use of the HUEBA. RESULTS: Ninety-eight percent of trainees found the classroom and in-water training to be "good/very good". Trainees found it to be "easy/very easy" to clear the HUEBA and breathe underwater in 84% and 64% of cases, respectively. Divers reported a greater ease in learning all the practical uses of the HUEBA except application of the nose clip. DISCUSSION: There were problems with the nose clip fitting incorrectly, and interference of the survival suit hood with the regulator, which subsequently have been resolved. When carefully applied, the introduction of the HUEBA into training for offshore oil and gas industry helicopter crew and passengers can be safely conducted.