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The combination of anastrozole and fulvestrant — which interfere with estrogen signaling by distinct mechanisms — increases progression-free and overall survival as compared with anastrozole alone or anastrozole followed by fulvestrant in women with HR-positive breast cancer. Endocrine therapy plays a central role in the treatment of hormone-receptor (HR)–positive metastatic breast cancer. 1 Selective aromatase inhibitors, such as anastrozole, letrozole, and exemestane, lower the estrogen level and are used as first-line endocrine treatments of HR-positive metastatic disease, owing to their superiority over tamoxifen. 1 Fulvestrant (Faslodex, AstraZeneca) is an analogue of estradiol that down-regulates the estrogen receptor by disrupting estrogen-receptor dimerization and accelerating degradation of the unstable fulvestrant–estrogen-receptor complex. 2 This effect leads to reduced cross-talk between the estrogen receptor and estrogen-independent growth factor signaling, thus delaying resistance to hormone therapy. 2 Clinically, fulvestrant at a dose of 250 mg monthly . . .

The addition of fulvestrant to anastrozole in postmenopausal women with hormone-receptor–positive metastatic breast cancer led to significantly longer progression-free survival (median, 15 months) and overall survival (median, 50 months) than anastrozole alone (13.5 and 42 months, respectively) when given as first-line endocrine therapy.

The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment of public health. Multiple authoritative bodies and scientific consensus groups have called for actions to prevent harmful exposures via improved policy approaches. We worked across multiple disciplines to develop consensus recommendations for health-protective, scientific approaches to reduce harmful chemical exposures, which can be applied to current US policies governing industrial chemicals and environmental pollutants. This consensus identifies five principles and scientific recommendations for improving how agencies like the US Environmental Protection Agency (EPA) approach and conduct hazard and risk assessment and risk management analyses: (1) the financial burden of data generation for any given chemical on (or to be introduced to) the market should be on the chemical producers that benefit from their production and use; (2) lack of data does not equate to lack of hazard, exposure, or risk; (3) populations at greater risk, including those that are more susceptible or more highly exposed, must be better identified and protected to account for their real-world risks; (4) hazard and risk assessments should not assume existence of a “safe” or “no-risk” level of chemical exposure in the diverse general population; and (5) hazard and risk assessments must evaluate and account for financial conflicts of interest in the body of evidence. While many of these recommendations focus specifically on the EPA, they are general principles for environmental health that could be adopted by any agency or entity engaged in exposure, hazard, and risk assessment. We also detail recommendations for four priority areas in companion papers (exposure assessment methods, human variability assessment, methods for quantifying non-cancer health outcomes, and a framework for defining chemical classes). These recommendations constitute key steps for improved evidence-based environmental health decision-making and public health protection.

AbstractObjectiveTo evaluate the effectiveness of remote proactive management of toxicities during chemotherapy for early stage breast cancer.DesignPragmatic, cluster randomised trial.Setting20 cancer centres in Ontario, Canada, allocated by covariate constrained randomisation to remote management of toxicities or routine care.ParticipantsAll patients starting adjuvant or neoadjuvant chemotherapy for early stage breast cancer at each centre. 25 patients from each centre completed patient reported outcome questionnaires.InterventionsProactive, standardised, nurse led telephone management of common toxicities at two time points after each chemotherapy cycle.Main outcome measuresThe primary outcome, cluster level mean number of visits to the emergency department or admissions to hospital per patient during the whole course of chemotherapy treatment, was evaluated with routinely available administrative healthcare data. Secondary patient reported outcomes included toxicity, self-efficacy, and quality of life.ResultsBaseline characteristics of participants were similar in the intervention (n=944) and control arms (n=1214); 22% were older than 65 years. Penetration (that is, the percentage of patients who received the intervention at each centre) was 50-86%. Mean number of visits to the emergency department or admissions to hospital per patient was 0.91 (standard deviation 0.28) in the intervention arm and 0.94 (0.40) in the control arm (P=0.94); 47% (1014 of 2158 patients) had at least one visit to the emergency department or a hospital admission during chemotherapy. Among 580 participants who completed the patient reported outcome questionnaires, at least one grade 3 toxicity was reported by 48% (134 of 278 patients) in the intervention arm and by 58% (163 of 283) in the control arm. No differences in self-efficacy, anxiety, or depression were found. Compared with baseline, the functional assessment of cancer therapy trial outcome index decreased by 6.1 and 9.0 points in the intervention and control participants, respectively.ConclusionsProactive, telephone based management of toxicities during chemotherapy did not result in fewer visits to the emergency department or hospital admissions. With the rapid rise in remote care because of the covid-19 pandemic, identifying scalable strategies for remote management of patients during cancer treatment is particularly relevant.Trial registrationClinicalTrials.gov NCT02485678.

Purpose Adherence to adjuvant endocrine therapy among post-menopausal breast cancer patients is an important survivorship care issue. We explored factors associated with endocrine therapy adherence and survival in a large real-world population-based study. Methods We used health administrative databases to follow women (aged ≥ 66 years) who were diagnosed with breast cancer and started on adjuvant endocrine therapy from 2005 to 2010. Adherence was measured by medical possession ratio (MPR) and characterized as low (< 39% MPR), intermediate (40–79% MPR), or high (≥ 80% MPR) over a 5-year period. We investigated factors associated with adherence using a multinomial logistic regression model. Factors associated with all-cause mortality (5 years after starting endocrine therapy) were investigated using a multivariable Cox proportional hazards model. Results We identified 5692 eligible patients starting adjuvant endocrine therapy who had low, intermediate, and high adherence rates of 13% ( n  = 749), 13% ( n  = 733), and 74% ( n  = 4210), respectively. Lower rates of adherence were associated with increased age [low vs. high adherence: odds ratio (OR) 1.03, 95% CI 1.02–1.05 (per year); intermediate vs. high adherence: OR 1.02, 95% CI 1.01–1.04 (per year)]. High adherence was associated with previous use of adjuvant chemotherapy (low versus high adherence OR 0.42, 95% CI 0.30–0.59) and short-term follow-up with a medical oncologist within 4 months of starting endocrine therapy (low versus high adherence OR 0.83, 95% CI 0.69–0.99). Unadjusted analysis showed increased survival among patients with high endocrine therapy adherence. However, an independent association was no longer clearly detected after controlling for confounders. Conclusion Interventions to improve adjuvant endocrine therapy adherence are warranted. Non-adherence may be a more significant issue among elderly patients. Short-term follow-up visit by a patient’s medical oncologist after starting endocrine therapy may help to improve compliance.

The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment of public health. Multiple authoritative bodies and scientific consensus groups have called for actions to prevent harmful exposures via improved policy approaches. We worked across multiple disciplines to develop consensus recommendations for health-protective, scientific approaches to reduce harmful chemical exposures, which can be applied to current US policies governing industrial chemicals and environmental pollutants. This consensus identifies five principles and scientific recommendations for improving how agencies like the US Environmental Protection Agency (EPA) approach and conduct hazard and risk assessment and risk management analyses: (1) the financial burden of data generation for any given chemical on (or to be introduced to) the market should be on the chemical producers that benefit from their production and use; (2) lack of data does not equate to lack of hazard, exposure, or risk; (3) populations at greater risk, including those that are more susceptible or more highly exposed, must be better identified and protected to account for their real-world risks; (4) hazard and risk assessments should not assume existence of a \"safe\" or \"no-risk\" level of chemical exposure in the diverse general population; and (5) hazard and risk assessments must evaluate and account for financial conflicts of interest in the body of evidence. While many of these recommendations focus specifically on the EPA, they are general principles for environmental health that could be adopted by any agency or entity engaged in exposure, hazard, and risk assessment. We also detail recommendations for four priority areas in companion papers (exposure assessment methods, human variability assessment, methods for quantifying non-cancer health outcomes, and a framework for defining chemical classes). These recommendations constitute key steps for improved evidence-based environmental health decision-making and public health protection.

Background: For patients with significant growth remaining, the Iliotibial Band ACL reconstruction technique has proven to be reliable procedure with minimal risk for growth disturbance. Recent dissection studies confirm the neuro-vascular bundle is within 1 cm of the ACL graft over the top position, confirming the importance of careful graft passage technique to avoid neurovascular injury. Purpose: The purpose of this study was to evaluate the over the top graft passage technique using pediatric 3-D knee models. Instrument placement for graft passage was assessed for its proximity to the posterior aspect of the femur, maintaining a safe distance from the neurovascular bundle. Materials and Methods: 3D knee models (ages 7, 9, 11 years) were printed from high resolution knee CT scans, including a hinge/pivot mechanism to allow for simulation of knee position during flexion and extension. Various curved tip instruments were used to evaluate the path of the graft passage, with several goals: 1. Allow the instrument to create a graft path through the posterior capsule in the most anatomic femoral position. 2. Keep the tip of the instrument close to posterior and lateral cortex of the femur, to avoid neurovascular injury. The instruments varied in design, arc of curvature, overall length, diameters. Results: Clamp passage was performed using a retrograde approach, i.e. through the notch, passing outside the periosteum of the postero-lateral femur (Figure 1). For some clamps, the arc of the curvature allowed for passage of the instrument with minimal risk of neurovascular injury. For some clamp configurations, the clamps deviated significant from the posterior aspect of the femur during graft passage, which may increase the risk of neurovascular bundle injury. In each case, an instrument was identified that met the criteria for safe passage, but different instruments were required based upon the size of the knee joint. Conclusions: The ITB ACL reconstruction is one of the best options for ACL reconstruction in the skeletally immature. The neurovascular structures are very close to the path for over the top graft placement. Due to the wide range of knee dimensions in this group, different clamp designs may be necessary for optimal over the top graft passage. 3D knee models may guide surgeons for procedure technique and optimal instrument selection for safe graft passage. Figure 1.