Sampada Gandhi

Acute decreases in proteasome pathway activity after inhalation of fresh diesel exhaust or secondary organic aerosol.

Background Epidemiologic studies consistently demonstrate an association between acute cardiopulmonary events and changes in air pollution; however, the mechanisms that underlie these associations are not completely understood. Oxidative stress and inflammation have been suggested to play a role in human responses to air pollution. The proteasome is an intracellular protein degradation system linked to both of these processes and may help mediate air pollution effects. Objectives In these studies, we determined whether acute experimental exposure to two different aerosols altered white blood cell (WBC) or red blood cell (RBC) proteasome activity in human subjects. One aerosol was fresh diesel exhaust (DE), and the other freshly generated secondary organic aerosol (SOA). Methods Thirty-eight healthy subjects underwent 2-hr resting inhalation exposures to DE and separate exposures to clean air (CA); 26 subjects were exposed to DE, CA, and SOA. CA responses were subtracted from DE or SOA responses, and mixed linear models with F-tests were used to test the effect of exposure to each aerosol on WBC and RBC proteasome activity. Results WBC proteasome activity was reduced 8% (p = 0.04) after exposure to either DE or SOA and decreased by 11.5% (p = 0.03) when SOA was analyzed alone. RBCs showed similar 8–10% declines in proteasome activity (p = 0.05 for DE alone). Conclusions Air pollution produces oxidative stress and inflammation in many experimental models, including humans. Two experimental aerosols caused rapid declines in proteasome activity in peripheral blood cells, supporting a key role for the proteasome in acute human responses to air pollution.

Acute Changes in Heart Rate Variability in Subjects With Diabetes Following a Highway Traffic Exposure

Objective: To pilot a protocol to evaluate acute cardiovascular effects in in-vehicle exposure to traffic air pollutants in people with diabetes. Methods: Twenty-one volunteers with type 2 diabetes were passengers on 90- to 110-minute car rides on a busy highway. We measured in-vehicle particle number and mass (PM2.5) nitrogen dioxide, and carbon monoxide and heart rate, heart rate variability (HRV), and blood pressure. Results: Compared with pre-ride measurements, we found a decrease in high frequency (HF) HRV from pre-ride to next day (ratio 0.66, 95% CI = 0.47 to 0.93) and an increase in low frequency to HF ratio at post-ride (ratio 1.92, 95% CI = 1.21 to 3.05) at post-ride. Interquartile range increases in measured pollutants were associated with next-day decreases in HR HRV. Conclusions: This protocol appears useful for assessing acute adverse cardiovascular effects of in-vehicle exposures among people who have diabetes.

Substantial under-treatment among women diagnosed with osteoporosis in a US managed-care population: a retrospective analysis

Abstract Background: Multiple therapies are approved for the treatment of osteoporosis (OP), but many patients with osteoporosis may not initiate treatment upon osteoporosis diagnosis. Objective: To characterize initiation of pharmacologic OP treatment among women within 1 year of OP diagnosis in a US managed care population. Research design and methods: The retrospective cohort study included women aged ≥55 years with a claims-documented diagnosis of OP who were naïve to OP medications prior to OP diagnosis (index date) during 2001–2010. Continuous enrollment for 12 months before (baseline) and after (follow-up) the index date was required. Patients who received OP medications but did not have an OP diagnosis were excluded. Differences in baseline characteristics between the treated and untreated cohorts were compared using Wilcoxon rank-sum (continuous variables) and chi-square tests (categorical variables). Main outcomes measures: During the follow-up period, the percentages of patients treated with bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid) and non-bisphosphonates (calcitonin, raloxifene, teriparatide) were determined. Results: A total of 65,344 patients, mean age 65.7 years, met study inclusion exclusion criteria. During the follow-up period, 42,033 patients (64.3%) received no OP medication and 23,311 patients (35.7%) received OP treatment. A total of 20,200 patients (30.9% of total study population) received bisphosphonates and 3111 (4.8% of total) patients received non-bisphosphonates as their index medication. At baseline, untreated patients were slightly older and had higher rates of hypertension, chronic inflammatory joint disease, diabetes mellitus, and gastrointestinal events (p ≤ 0.01) compared with treated patients. Conclusions: Among women aged ≥55 years in a US managed-care population, 64.3% received no pharmacologic treatment within 1 year after being diagnosed with OP. The authors were not able to determine if untreated patients did not receive or did not fill a prescription. Further research is needed to understand the barriers to OP treatment and reasons for non-treatment.

Challenges in implementing and maintaining osteoporosis therapy.

In the United States, an estimated 19% of older men and 30% of older women are at elevated risk of osteoporotic fracture and considered to be eligible for treatment. The burden of osteoporosis is similar in Europe and is projected to rise worldwide, with aging populations and increasing fracture rates accompanying urbanization. Notwithstanding its high prevalence, osteoporosis is often underdiagnosed and undertreated. Moreover, even when the diagnosis is made and the decision is taken to treat, there are remaining challenges in implementing therapy for osteoporosis. Several patient populations are particularly challenging for clinicians to treat and require further study with regard to osteoporosis therapy. These include the very elderly, who face challenges relating to adherence; men, in whom osteoporosis remains under-recognized; patients with glucocorticoid-induced osteoporosis or renal impairment, who are at increased risk of fracture; patients with preexisting gastrointestinal problems who cannot tolerate existing orally administered osteoporosis therapies; and high-risk patients who show inadequate response to therapy. Moreover, poor adherence and poor persistence with osteoporosis medications are common and result in an increased risk of fracture, higher medical costs, and increased hospitalizations. Once the decision to institute therapy is made, patient education about osteoporosis and fracture risk should be provided. This is particularly important for men, who may not be aware that osteoporosis can be a concern. Secondary prevention programs, including fracture liaison services and bone therapy groups, can help to improve adherence to therapy. Further study is needed to guide the treatment of men, the very elderly, patients with glucocorticoid-induced osteoporosis and renal impairment, high-risk patients not well-controlled despite therapy, and patients with preexisting gastrointestinal conditions. Moreover, therapies are needed that are viewed as effective and safe by both physicians and patients, and as convenient to take by patients.

Use of Adjuvant Systemic Therapy for Early Breast Cancer Among Women 65 Years of Age and Older

BACKGROUND The National Institutes of Health (NIH) consensus statement recommends adjuvant therapy for early breast cancer irrespective of age. However, the actual use of such therapy is not well documented among women over 65 years of age. METHODS We studied the frequency of use of adjuvant therapy and report the receipt of this therapy among 200 women aged > or = 65 years diagnosed with early breast cancer who were identified from the New Jersey State Cancer Registry. RESULTS In this population, 28% of patients received chemotherapy alone or in combination with hormonal therapy, whereas 42% received hormonal therapy alone. Less than half of the women with estrogen receptor-negative tumors received chemotherapy alone or in combination with hormonal treatment. Adjuvant therapy was not prescribed in 30% of patients. CONCLUSIONS Despite NIH recommendations, the frequency of use of adjuvant therapy in New Jersey is low among women over 65 years of age, regardless of their receptor status.

Organizational Factors and Office Workers' Health After the World Trade Center Terrorist Attacks : Long-Term Physical Symptoms, Psychological Distress, and Work Productivity

Objective: To assess if organizational factors are predictors of workers’ health and productivity after the World Trade Center attacks. Methods: We conducted a survey of 750 workers and compared those who had direct exposures to the World Trade Center attacks (south of Canal Street workers; primary victims) with those less directly exposed (north of Canal Street workers; other victims and non-victims). Results: South of Canal Street workers reported headache more frequently than north of Canal Street workers did (P = 0.0202). Primary victims reported headache and cough more frequently than did other victims and non-victims (P = 0.0086 and 0.0043, respectively). Defensive organizational culture was an independent predictor of cough and job stress, and job stress was an independent predictor of on-the-job productivity losses. Conclusion: Organizational variables may modify health and productivity outcomes after a large-scale traumatic event in the workplace.

Plasma nitrite is an indicator of acute changes in ambient air pollutant concentrations.

Abstract Context: Endothelial dysfunction has been suggested as a potential mechanism by which ambient air pollution may cause acute cardiovascular events. Recently, plasma nitrite has been developed as a marker of endothelial dysfunction. Objectives: We examined the changes in plasma nitrite concentration associated with increases in ambient air pollutant concentrations in the previous 7 d. Materials and methods: We linked up to three measurements of plasma nitrite concentrations obtained from 49 students to 24-h average concentrations of five criteria air pollutants [particle mass < 2.5 µm in aerodynamic diameter (PM2.5), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3)] measured at two monitoring sites closest to Rutgers University campus (6–15 miles) in New Jersey during the years 2006–2009. We examined the change in plasma nitrite associated with each interquartile-range (IQR) increase in pollutant concentration in the previous 24 h and six preceding 24- h periods, using linear mixed models. Results: IQR increases in mean PM2.5 (7.0 µg/m3) and CO (161.7 parts per billion) concentrations in the first 24 h before the plasma nitrite measurement were associated with increased plasma nitrite concentrations (PM2.5: 15.5 nanomolar; 95% confidence interval (CI): 2.4, 28.5; CO: 15.6 nanomolar; 95% CI: 2.4, 28.9). Increased plasma nitrite associated with IQR increases in O3 and SO2 concentrations over longer lags were observed. Discussion and conclusion: Rapid increases in plasma nitrite following exposure to ambient air pollutants support the hypothesis that ambient air pollution is associated with inducible nitric oxide synthase-mediated systemic inflammation in humans.