Ozone sensitivity to high energy demand day electricity and onroad emissions during LISTOS.

IMPLICATION STATEMENT: High-resolution coupled meteorology-chemistry modeling in the New York City and surrounding areas is used to model changes in ozone air quality resulting from region-wide onroad transportation emission reductions and NOX reductions from high energy demand day (HEDD) electricity generating units (EGUs). Although reducing onroad emissions by 90% produces the largest change in ozone concentrations, the results also suggest that the ozone photochemical regime becomes more NOx-sensitive as emissions from major regional sectors like onroad transportation continue to decline. Despite being highly localized and variable, emissions from HEDD EGUs can have an added impact on reducing ambient ozone concentrations. As the ozone production regime in the region shifts from VOC-sensitive to NOx-sensitive, the impacts of NOx-titration in the urban core weaken and ozone is more likely to decline with a decrease in NOx emissions such as from HEDD units.

Investigating Changes in Ozone Formation Chemistry during Summertime Pollution Events over the Northeastern United States.

Understanding the local-scale spatial and temporal variability of ozone formation is crucial for effective mitigation. We combine tropospheric vertical column densities (VCDTrop) of formaldehyde (HCHO) and nitrogen dioxide (NO2), referred to as HCHO-VCDTrop and NO2-VCDTrop, retrieved from airborne remote sensing and the TROPOspheric Monitoring Instrument (TROPOMI) with ground-based measurements to investigate changes in ozone precursors and the inferred chemical production regime on high-ozone days in May-August 2018 over two Northeast urban domains. Over New York City (NYC) and Baltimore/Washington D.C. (BAL/DC), HCHO-VCDTrop increases across the domain, but higher NO2-VCDTrop occurs mainly in urban centers on ozone exceedance days (when maximum daily 8 h average (MDA8) ozone exceeds 70 ppb at any monitor in the region). The ratio of HCHO-VCDTrop to NO2-VCDTrop, proposed as an indicator of the sensitivity of local surface ozone production rates to its precursors, generally increases on ozone exceedance days, implying a transition toward a more NOx-sensitive ozone production regime that should lead to higher efficacy of NOx controls on the highest ozone days in NYC and BAL/DC. Warmer temperatures and enhanced influence from emissions in the local boundary layer on the high-ozone days are accompanied by slower wind speeds in BAL/DC but stronger, southwesterly winds in NYC.

Treatment Outcomes in Patients with Metastatic Neuroendocrine Tumors: a Retrospective Analysis of a Community Oncology Database.

PURPOSE: Metastatic neuroendocrine tumors (mNETs) are rare, heterogeneous tumors that present diagnostic and treatment challenges, with limited data on the management of mNETs in clinical practice. The present study was designed to identify current diagnostic and treatment patterns in mNET patients treated in the US community oncology setting. METHODS: Patient-level data was collected from medical records of adults with mNETs from the Vector Oncology Data Warehouse, a comprehensive US community oncology network database. RESULTS: Of the 263 patients included (median follow-up, 22 months; range, 0.1-193.9), 30.4% (80/263) had intestinal tumors, 11.0% (29/263) had pancreatic, and 58.6% (154/263) had tumors of other or unknown location. Progression-free survival (PFS) from the start of first-line therapy differed significantly by tumor grade (log rank P = 0.0016) and location (P = 0.0044), as did overall survival (OS) (grade, P < 0.0001; location, P = 0.0068). Median PFS and OS for patients with undocumented tumor grade were shorter than for patients with G1/G2 tumors and longer than patients with G3 tumors. Median PFS and OS for patients with other or unknown tumors were shorter than for patients with intestinal tumors. CONCLUSIONS: While potentially confounded by the high number of patients with other or unknown tumor locations, this retrospective study of patients in a US community oncology setting identified the importance of awareness of tumor grade and tumor location at diagnosis, as these were direct correlates of PFS and OS.

Treatment Patterns and Outcomes in Stage IV Bladder Cancer in a Community Oncology Setting: 2008-2015.

INTRODUCTION: Current real-world data regarding treatment patterns in advanced bladder cancer in the community setting are limited. This study describes patient characteristics, treatment patterns, and effectiveness outcomes for stage IV bladder cancer in the community setting. METHODS: Medical records data of adults diagnosed with stage IV bladder cancer between January 1, 2008 and June 1, 2015 were retrospectively collected from a network of United States community oncology practices. Patient characteristics, treatment patterns, and efficacy outcomes were assessed. Across-group comparisons were conducted using bivariate analyses. Kaplan-Meier and Cox regression analyses of progression-free survival and overall survival (OS) were conducted. RESULTS: Of 508 patients (mean age, 70 ± 11 years), 75.2% were male, 79.1% white, 15.4% black, and 71.5% were ≥ 65 years. The most prevalent comorbidities were diabetes (23.4%) and renal disease (16.5%). Overall, 56% of patients received first-line platinum-based chemotherapy; the most common regimen was gemcitabine/carboplatin (23.6%), followed by gemcitabine/cisplatin (17%). The median OS was 9.4 months from stage IV bladder cancer diagnosis and 8.4 months from start of first-line therapy. Cox regression analysis of OS from diagnosis showed a higher risk of death for patients with no treatment (hazard ratio [HR], 2.06; P < .0001) or other treatment (HR, 1.83; P = .002) versus cisplatin and for patients with impaired performance (HR, 2.05; P < .0001). CONCLUSION: Platinum-based chemotherapy was the most prescribed treatment for stage IV bladder cancer in the community setting. Several patients were not treated with any chemotherapy, although we did not observe the reason for no treatment. This study highlights an unmet need in this population, particularly in a relapsed/refractory setting, and the need for improvement in outcomes.

Effectiveness Outcomes in Patients With Recurrent or Refractory Head and Neck Cancers: Retrospective Analysis of Data From a Community Oncology Database.

PURPOSE: The purpose of this study was to provide an understanding of the effectiveness of existing therapies in patients with advanced head and neck cancer (HNC), particularly in clinical practice. METHODS: Data from the electronic medical records of adult patients diagnosed with locally advanced or metastatic (Stage III-IVc) HNC between January 1, 2007, and October 1, 2015, were retrospectively collected from a network of community oncology practices in the United States. Eligible patients experienced disease progression despite having received prior systemic therapy. Kaplan-Meier and Cox regression analyses of progression-free survival (PFS) and overall survival (OS) were conducted. Patient-reported outcomes were also collected. FINDINGS: The study included 462 patients (median age 61.0 years; 80.7% male; 77.1% white). Most patients had a history of tobacco use (41.8% current, 41.8% past), and human papillomavirus testing was infrequent overall (11.0%). The median overall duration of follow-up was 16.4 months (range, 2.3-85.2 months). Median PFS values were 8.45 months with first-line treatment and 5.33 months with second-line treatment. PFS with first-line treatment was significantly associated with primary tumor location, performance status, and tobacco use. Performance status was a predictor of PFS in second-line treatment. Median OS values were 21.04 and 9.53 months from the start of the first and second lines of therapy, respectively. Abuse/excessive use of alcohol, older age, and impaired performance status were associated with a significantly increased risk for death in outcomes analyses. Outcomes were worse among patients initially diagnosed with Stage IVc disease versus those who progressed to Stage IVc. Past tobacco use and alcohol abuse were associated with worse patient-reported symptoms such as dry mouth and sore throat (smoking) and trouble swallowing (alcohol). IMPLICATIONS: This study of data from clinical practice shows that there remains a large unmet need for effective therapeutic options in advanced HNC. Patients' characteristics such as alcohol use and performance status were statistically significant predictors of PFS and OS in Stage III-IVc HNC.

Patient Characteristics and Costs in Recurrent or Refractory Head and Neck Cancer: Retrospective Analysis of a Community Oncology Database.

PURPOSE: The goal of this study was to describe patient characteristics, health resource utilization (HRU), and costs associated with treating recurrent or refractory head and neck cancer (HNC) among patients with disease progression in the community oncology setting. METHODS: This retrospective observational study was conducted by using data from the Vector Oncology Data Warehouse. Patients had been diagnosed with locally advanced or metastatic (stage III-IVc) HNC between January 1, 2007, and October 1, 2015. Patients also had evidence of at least 1 systemic anticancer therapy regimen following the diagnosis of advanced HNC, with at least 1 disease progression. Costs, treatment patterns, and HRU were evaluated beginning with diagnosis of advanced HNC through 3 lines of therapy. Costs of surgery or radiation were not available for inclusion in the analysis. Total cost for the study period and cost per month were analyzed by using a generalized linear regression model. FINDINGS: The study included 462 patients (median age, 61 years; range, 26-99 years); of these, 81% were male, 77% were white, and 21% were black. At initial diagnosis, the most frequent tumor locations were the hypopharynx/larynx (31%) and the oropharynx (31%). Human papilloma virus testing was most frequent among the oropharynx group (22% tested, 52% positive). Overall, 42% were current tobacco users and 22% were current or past alcohol abusers/excessive users. Platinum-based combination therapies were the most frequently administered chemotherapy in both first (42%) and second (40%) lines of treatment. Through the overall study period (mean, 20.5 months), 74% of patients were hospitalized, 19% had an emergency department visit, and 100% had an office visit. The overall mean (SD) duration of hospital stay was 12.6 days, and the median number of office visits per patient was 35. The mean monthly health care cost for the overall study period was $14,391 (95% CI, 12,739-16,044). Hospitalization costs represented ~57% of the total expenditures. Statistically significant predictors of higher overall cost included primary tumor location in the oral cavity, history of alcohol abuse/excess use, use of cetuximab, and higher comorbidity index. Older age and being stage IV versus other stages of disease at diagnosis were associated with lower overall cost. IMPLICATIONS: These data suggest that costs of care in patients with recurrent or refractory HNC are related to patient characteristics and treatment patterns. Identification of factors contributing to the costs of care in HNC may provide a useful foundation for developing strategies to control rising costs.

Effect of Brain Metastasis on Patient-Reported Outcomes in Advanced NSCLC Treated in Real-World Community Oncology Settings.

INTRODUCTION: Health-related quality of life (HRQOL) in advanced non-small-cell lung cancer (NSCLC) might be affected by the presence of brain metastasis (BM). We report findings from a prospective observational study that examined HRQOL in patients newly diagnosed with advanced NSCLC, with or without baseline BM, through 1 year of follow-up. PATIENTS AND METHODS: Patients starting first-line treatment of stage IIIB/IV NSCLC were prospectively enrolled and consented at 34 US-based community oncology practices. Data on patient-reported outcomes (PROs) were collected once per cycle during treatment, and at each visit after discontinuation. PROs included the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and Lung Cancer Module (QLQ-LC13), the Lung Cancer Module of the M.D. Anderson Symptom Inventory (MDASI-LC), and the Rotterdam Activity Level Scale (RALS). Linear mixed models were used to examine the effect of baseline BM, including differences in change over time. RESULTS: One hundred forty-five patients provided follow-up PRO data, comprising 1100 individual surveys and 32 PRO end points. The patient group was 58.6% (n = 85) male, and 86.2% (n = 125) Caucasian. Patients with baseline BM were younger (61.3 vs. 65.8 years; P = .040) with more concurrent radiotherapy (59.4% [n = 19] vs. 15.9% [n = 18]; P < .0001). Results showed minimal differences in baseline HRQOL. Of the 20 measures that showed significant group differences in HRQOL over time, 18 showed greater deterioration for patients with baseline BM. These 18 measures included all QLQ-C30 composite measures except Global Health Status, all MDASI-LC measures, and the RALS (all P < .05). For these measures, the average 1-year deterioration in patients with baseline BM was 19.4%. CONCLUSION: Newly diagnosed advanced NSCLC patients with baseline BM experienced a significantly faster and clinically meaningful deterioration in PRO-based HRQOL compared with those without baseline BM.

Effectiveness outcomes and health related quality of life impact of disease progression in patients with advanced nonsquamous NSCLC treated in real-world community oncology settings: results from a prospective medical record registry study.

BACKGROUND: Treatment options for advanced nonsquamous non-small cell lung cancer (NSCLC) in the first line include platinum-based doublet therapy with or without bevacizumab. This study examined efficacy outcomes and patient reported outcomes (PROs) in a community oncology patient sample. METHODS: Advanced nonsquamous NSCLC patients from 34 U.S. community oncology practices treated in first line with bevacizumab regimens (A platinum doublet; gemcitabine doublet; pemetrexed with platinum) or non-bevacizumab regimens (B platinum doublet; gemcitabine doublet; C pemetrexed with platinum) were recruited for this prospective study. Patient characteristics and clinical outcomes were accessed from routine care records. Three validated and widely used PRO measures of health related quality of life (HRQOL) and symptom burden were collected prospectively at each visit and up to one-year follow-up. Effectiveness outcomes were progression free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier and Cox regression methods. PROs were analyzed with linear mixed model regression to examine changes over time, and the effect of disease progression. RESULTS: Of 147 patients in the study, 145 provided PRO data. Patients in treatment groups were: A (n = 66, 44.9%); B (n = 25, 17.0%); C (n = 56, 38.1%). A was associated with significantly longer OS than B (HR = 0.341, p = 0.0012), and significantly longer than C (HR = 0.602, p = 0.0354). PFS results were similar. Irrespective of regimen group and on 12/32 measures, patients showed significant and clinically meaningful worsening of symptoms and HRQOL at disease progression. After disease progression, the pattern of symptom and HRQOL change showed continued worsening. CONCLUSIONS: Bevacizumab-containing regimens were associated with longer PFS and OS compared with non-bevacizumab regimens. PRO measures show disease progression is associated with worsening HRQOL. Delaying disease progression can sustain better HRQL and reduce symptom burden.

Analysis of the psychological impact of cancer-related symptoms on patients with non-small cell lung cancer.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience adverse physical symptoms because of cancer, cancer treatment, and comorbidities. The relations among Cancer-Related Symptoms, Functional Impairment, and Psychological Symptoms in patients with NSCLC is not well understood. METHODS: Retrospective analysis of patient-reported symptoms with the 38-item Patient Care Monitor survey, collected in routine clinical care for 1138 patients with NSCLC at eight US community oncology practices. Study sample was randomly split, and structural equation models examined the direct and mediated effects of Cancer-Related Symptoms and Functional Impairment on symptoms of acute distress (Distress) and depression (Despair) in the training sample. The training model was cross validated in testing sample. Results are presented for the full model using the entire sample. RESULTS: Patients were 48.3% female, with mean age of 66.0 years. The most common comorbidities were anemia (60.8%) and respiratory disease (24.5%). Severity of Cancer-Related Symptoms was strongly and positively related to Functional Impairment and Psychological Symptoms in both training and testing models. The modeled effect of Functional Impairment on Distress and Despair was significant in the overall model using the total sample, and significant or near-significant in the training and testing models. The mediated effect of Cancer-Related Symptoms by Functional Impairment tended to be weaker than its direct modeled effect on Distress and Despair. CONCLUSIONS: Despite prior research suggesting that Functional Impairment plays a larger role than symptom burden in depression in NSCLC, the independent modeled effects of Functional Impairment were no greater than the direct modeled effects of Cancer-Related Symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Impacts of potential CO2-reduction policies on air quality in the United States.

Impacts of emissions changes from four potential U.S. CO2 emission reduction policies on 2050 air quality are analyzed using the community multiscale air quality model (CMAQ). Future meteorology was downscaled from the Goddard Institute for Space Studies (GISS) ModelE General Circulation Model (GCM) to the regional scale using the Weather Research Forecasting (WRF) model. We use emissions growth factors from the EPAUS9r MARKAL model to project emissions inventories for two climate tax scenarios, a combined transportation and energy scenario, a biomass energy scenario and a reference case. Implementation of a relatively aggressive carbon tax leads to improved PM2.5 air quality compared to the reference case as incentives increase for facilities to install flue-gas desulfurization (FGD) and carbon capture and sequestration (CCS) technologies. However, less capital is available to install NOX reduction technologies, resulting in an O3 increase. A policy aimed at reducing CO2 from the transportation sector and electricity production sectors leads to reduced emissions of mobile source NOX, thus reducing O3. Over most of the U.S., this scenario leads to reduced PM2.5 concentrations. However, increased primary PM2.5 emissions associated with fuel switching in the residential and industrial sectors leads to increased organic matter (OM) and PM2.5 in some cities.

Regional air quality management aspects of climate change: impact of climate mitigation options on regional air emissions.

We investigate the projected impact of six climate mitigation scenarios on U.S. emissions of carbon dioxide (CO2), sulfur dioxide (SO2), and nitrogen oxides (NOX) associated with energy use in major sectors of the U.S. economy (commercial, residential, industrial, electricity generation, and transportation). We use the EPA U.S. 9-region national database with the MARKet Allocation energy system model to project emissions changes over the 2005 to 2050 time frame. The modeled scenarios are two carbon tax, two low carbon transportation, and two biomass fuel choice scenarios. In the lower carbon tax and both biomass fuel choice scenarios, SO2 and NOX achieve reductions largely through pre-existing rules and policies, with only relatively modest additional changes occurring from the climate mitigation measures. The higher carbon tax scenario projects greater declines in CO2 and SO2 relative to the 2050 reference case, but electricity sector NOX increases. This is a result of reduced investments in power plant NOX controls in earlier years in anticipation of accelerated coal power plant retirements, energy penalties associated with carbon capture systems, and shifting of NOX emissions in later years from power plants subject to a regional NOX cap to those in regions not subject to the cap.

Treatment Patterns and Health Resource Utilization Among Patients Diagnosed With Early Stage Resected Non-Small Cell Lung Cancer at US Community Oncology Practices.

UNLABELLED: Data on adjuvant therapy in resected non-small cell lung cancer (NSCLC) in routine practice are lacking in the United States. This retrospective observational database study included 609 community oncology patients with resected stage IB to IIIA NSCLC. Use of adjuvant therapy was 39.1% at disease stage IB and 64.9% to 68.2% at stage II to IIIA. The most common regimen at all stages was carboplatin and paclitaxel. BACKGROUND: Platin-based adjuvant chemotherapy has extended survival in clinical trials in patients with completely resected non-small cell lung cancer (NSCLC). There are few data on the use of adjuvant therapy in community-based clinical practice in the United States. MATERIALS AND METHODS: This was a retrospective observational study using electronic medical record and billing data collected during routine care at US community oncology sites in the Vector Oncology Data Warehouse between January 2007 and January 2014. Patients aged ≥ 18 years with a primary diagnosis of stage IB to IIIA NSCLC were eligible if they had undergone surgical resection. Treatment patterns, health care resource use, and cost were recorded, stratified by stage at diagnosis. RESULTS: The study included 609 patients (mean age, 64.8 years, 52.9% male), of whom 215 had stage IB disease, 130 stage IIA/II, 110 stage IIB, and 154 stage IIIA. Adjuvant systemic therapy after resection was provided to 345 (56.7%) of 609 patients, with lower use in patients with stage IB disease (39.1%) than stage II to IIIA disease (64.9-68.2%) (P < .0001). The most common adjuvant regimen at all stages was the combination of carboplatin and paclitaxel. There were no statistically significant differences in office visits or incidence of hospitalization by disease stage. During adjuvant treatment, the total monthly median cost per patient was $17,389.75 (interquartile range, $8,815.61 to $23,360.85). CONCLUSION: Adjuvant systemic therapy was used in some patients with stage IB NSCLC and in the majority of patients with stage IIA to IIIA disease. There were few differences in regimen or health care resource use by disease stage.

Phase 1b study of safety, tolerability and efficacy of R1507, a monoclonal antibody to IGF-1R in combination with multiple standard oncology regimens in patients with advanced solid malignancies.

BACKGROUND: R1507 is a human IgG1 Mab that binds to the insulin-like growth factor-1 receptor (IGF-1R) and inhibits IGF-1- or IGF-2-mediated anchorage-independent growth of malignant cells. A phase 1b study evaluated the safety, tolerability and efficacy of R1507 in combination with multiple standard oncology regimens. METHODS: R1507 (3, 5, 9, 10 and 16 mg/kg IV, Q2 W or Q3 W) was added to six treatment regimens: gemcitabine + erlotinib (GE); paclitaxel + bevacizumab (PB); carboplatin + etoposide (CE); mFOLFOX6 + bevacizumab (FB); capecitabine + trastuzumab (CT); and sorafenib (S). If tolerable, R1507 dose was escalated utilizing a 3 + 3 + 6 and a 3 + 9 design. RESULTS: A total of 104 patients enrolled into regimens 1-6: 93 % were non-recent diagnoses. Eighteen withdrew for safety [one death, 17 adverse events (AEs)]. A total of 1,337 AEs any grade, across regimens and doses were nausea, vomiting and diarrhea. A total of 123 had grade ≥3 AEs (n = 28 dose level 1; n = 95 dose level 1) and in 60 patients were myelosuppression, fatigue and mucosal inflammation. ORR (PR plus SD) of evaluable patients across six regimens was 36 % with five PRs: regimens PB (non-small cell lung cancer, nasopharyngeal cancer), CE (melanoma), FB (colon cancer) and S (GIST). The GIST pt (>4 prior therapies) had a PR for 3 years. Three patients (breast cancer, melanoma and adenoid cystic carcinoma) were on study for >1 year; 76 % of patients had SD or better for 4 months. CONCLUSIONS: R1507 added to six standard oncology regimens was well tolerated with an ORR of 36 %.

Willingness to pay to prevent chemotherapy induced nausea and vomiting among patients with breast, lung, or colorectal cancer.

OBJECTIVE: Understanding the value patients place on avoiding various aspects of chemotherapy induced nausea and vomiting (CINV) can help medical professionals assess whether current and emerging treatments are acceptable based on their costs and expected effects. Little is known, however, about the value patients place on avoiding various aspects of CINV. The current study helps fill this gap in the literature. METHODS: 301 patients completed a discrete-choice conjoint survey. Patients viewed 25 conjoint tasks, each containing two descriptions of CINV, and indicated which they preferred. The descriptions combined levels from eight CINV attributes (likelihood of nausea, duration of nausea, severity of nausea, likelihood of vomiting, duration of vomiting, severity of vomiting, need to seek treatment for dehydration, and out-of-pocket treatment costs). RESULTS: Cost contributed more to patient choices than any other single attribute. The combined effect of the likelihood, duration, and severity attributes for nausea, however, was a stronger driver of patient choices than cost, as was the combined effect of the likelihood, duration, and severity attributes for vomiting. The nausea attributes also were a stronger driver of patient choices than the vomiting attributes. Patients were willing to pay to avoid increases in all attributes, except likelihood of vomiting, where the result was not statistically different from zero. Willingness-to-pay varied by income, disease stage, Eastern Cooperative Oncology Group performance status, chemotherapy status, and whether patients worked while on chemotherapy. LIMITATIONS: Although the study used a convenience sample, data were collected from several geographically dispersed U.S. oncology clinics. CONCLUSIONS: Several antiemetics are now available at different price points. This study assesses the value patients place on their benefits and may be used to inform decisions about the management of CINV.

The association of rash severity with overall survival: findings from patients receiving erlotinib for pancreatic cancer in the community setting.

OBJECTIVES: This retrospective study examined pancreatic cancer patients who received combination gemcitabine and erlotinib to determine if the association between rash and outcomes observed in clinical trials would be observed in 'real-world' community oncology settings. METHODS: Medical records from 10 community oncology practices were used to identify eligible patients. Rash severity was classified as High (moderate/severe) versus Low (absent/mild) based on medical record review. Kaplan-Meier analysis assessed progression-free survival (PFS) and overall survival (OS) by rash status from a landmark of 42 days after treatment initiation. Cox regression with time-varying covariates tested whether high-severity rash predicted longer OS and PFS. RESULTS: The High Severity group (n = 34) had longer median OS from the landmark than the Low Severity group (n = 134; 7.58 months vs 5.03 months, P = 0.0339). Cox regression analysis (n = 174) confirmed a reduced risk of death with High Rash Severity (hazard ratio [HR] = 0.67, P = 0.0389). Progression-free survival results showed a similar pattern (median PFS 2.37 months from landmark vs 2.04 months for High vs Low Severity groups, P = 0.0485). CONCLUSIONS: Results from this community sample were consistent with findings from randomized clinical trials, showing that longer OS is predicted by high-severity rash in erlotinib-treated pancreatic cancer patients.

Relationship between incidence of fracture and health-related quality-of-life in metastatic breast cancer patients with bone metastases.

OBJECTIVE: This retrospective observational study describes treatment patterns and longitudinal health-related quality-of-life (HRQoL) among metastatic breast cancer patients with bone metastasis from nine community oncology clinics. METHODS: For description of treatment patterns, patients were classified as treated if they started zoledronic acid within 60 days of diagnosis of bone metastasis, were considered untreated if they had not, and were considered unclassified if they died or experienced fracture before 60 days had elapsed. Medical record review provided demographic and disease characteristics as well as history of treatment. Patients completed Patient Care Monitor (PCM) assessments of patient reported outcomes during routine care for up to 2 years from the date of bone metastasis diagnosis. RESULTS: The overall rate of fracture in the sample was 17.4%. Of the 321 patients enrolled, 160 were treated as of 60 days after diagnosis of bone metastasis, 147 were untreated, and 14 were unclassified. Of the 147 untreated as of 60 days, 82 did eventually receive zoledronic acid. More than half of all patients treated with zoledronic acid delayed the start of treatment by more than 30 days after diagnosis of bone metastasis. Patients who had a fracture showed decreased mobility and increased pain and anxiety at fracture, with recovery taking ~16 months. LIMITATIONS: Key limitations included: convenience sample with information limited to medical record content, low rate of observed fractures possibly due to limited 2-year follow-up, and exclusion of non-zoledronic acid bisphosphonate use. CONCLUSIONS: Whereas the proportion of patients experiencing a fracture was small, the impact of fracture on HRQoL was significant and was more prominently seen to impact specific dimensions of HRQoL.

Efficacy and safety of anidulafungin in elderly, critically ill patients with invasive Candida infections: a post hoc analysis.

Post hoc analysis of a non-comparative, prospective, multicentre, phase IIIb study was performed to compare efficacy and safety of anidulafungin in elderly (≥65 years) versus non-elderly (<65 years) Intensive Care Unit (ICU) patients with candidaemia/invasive candidiasis (C/IC). Adult ICU patients with confirmed C/IC meeting ≥1 of the following criteria were enrolled: post-abdominal surgery; solid tumour; renal/hepatic insufficiency; solid organ transplantation; neutropenia; age ≥65 years. Patients received anidulafungin (200 mg on Day 1, 100 mg/day thereafter) for ≥10 days followed by optional azole step-down therapy for a total treatment duration of 14-56 days. The primary efficacy endpoint was global (clinical and microbiological) response at the end of all therapy (EOT). Primary efficacy analysis was performed in the modified intent-to-treat (mITT) population (n=170), excluding unknown and missing responses. In total, 80 patients (47.1%) were aged ≥65 years and 90 (52.9%) were aged <65 years; the mean age difference between the two groups was 21.9 years. Global success at EOT in mITT patients was similar in elderly (68.1%) and non-elderly (70.7%) patients (P=0.719). However, global success rates were significantly lower in elderly versus non-elderly patients at 2 and 6 weeks after EOT (P=0.045 and P=0.016, respectively). Ninety-day survival was significantly lower (P=0.006) for elderly (42.8%) versus non-elderly patients (63.3%). The incidence and profile of adverse events were similar in elderly and non-elderly patients. Anidulafungin was effective and safe for treatment of C/IC in elderly ICU patients, despite higher baseline severity of illness scores.

Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem-cell transplantation.

Antifungal prophylaxis for allogeneic haematopoietic stem-cell transplant (alloHCT) recipients should prevent invasive mould and yeast infections (IFIs) and be well tolerated. This prospective, randomized, open-label, multicentre study compared the efficacy and safety of voriconazole (234 patients) versus itraconazole (255 patients) in alloHCT recipients. The primary composite endpoint, success of prophylaxis, incorporated ability to tolerate study drug for ≥ 100 d (with ≤ 14 d interruption) with survival to day 180 without proven/probable IFI. Success of prophylaxis was significantly higher with voriconazole than itraconazole (48·7% vs. 33·2%, P < 0·01); more voriconazole patients tolerated prophylaxis for 100 d (53·6% vs. 39·0%, P < 0·01; median total duration 96 vs. 68 d). The most common (>10%) treatment-related adverse events were vomiting (16·6%), nausea (15·8%) and diarrhoea (10·4%) for itraconazole, and hepatotoxicity/liver function abnormality (12·9%) for voriconazole. More itraconazole patients received other systemic antifungals (41·9% vs. 29·9%, P < 0·01). There was no difference in incidence of proven/probable IFI (1·3% vs. 2·1%) or survival to day 180 (81·9% vs. 80·9%) for voriconazole and itraconazole respectively. Voriconazole was superior to itraconazole as antifungal prophylaxis after alloHCT, based on differences in the primary composite endpoint. Voriconazole could be given for significantly longer durations, with less need for other systemic antifungals.

Long-term effect of latanoprost/timolol fixed combination in patients with glaucoma or ocular hypertension: a prospective, observational, noninterventional study.

BACKGROUND: Prospective, observational studies that enroll large numbers of patients with few exclusion criteria may better reflect actual ongoing clinical experience than randomized clinical trials. Our purpose was to obtain efficacy and safety information from a cohort of subjects exposed to latanoprost/timolol fixed combination (FC) for ≥18 months using a prospective, observational design. METHODS: In all, 577 office-based ophthalmologists in Germany switched 2339 patients with glaucoma or ocular hypertension to latanoprost/timolol FC for medical reasons. Follow-up visits were scheduled for every 6 months over 24 months; physicians followed usual care routines. Intraocular pressure (IOP), visual field status, optic nerve head findings, and adverse events were recorded. Efficacy parameters were evaluated for the per protocol (PP) population; the safety population included subjects receiving ≥1 drop of FC. Physicians rated efficacy, tolerability, and subject compliance at month 24. RESULTS: Of the 2339 subjects switched to latanoprost/timolol FC (safety population), the primary reasons for switching were inadequate IOP reduction (78.2%) and desire to simplify treatment with once-daily dosing (29.4%; multiple reasons possible). In all, 1317 (56.3%) subjects completed the study, and 1028 (44.0%) were included in the PP population. Most discontinuations were due to loss to follow-up. Change in mean IOP from baseline to month 6 was -4.0 ± 4.31 mmHg, a reduction that was maintained throughout (P < 0.05 for change at all time points). By investigator assessments, optic disc parameters and visual field were stable over 24 months, and there was no relationship between IOP reduction over 24 months and development of a visual field defect. More than 90% of physicians rated latanoprost/timolol FC as "very good" or "good" for efficacy (PP population), tolerability, and compliance. The FC was safe and well tolerated. No change in iris color was reported by most subjects (83.1%) at month 24. CONCLUSIONS: Over 24 months, latanoprost/timolol FC effectively lowers IOP levels and is well tolerated in patients with glaucoma or ocular hypertension who change from their previous ocular hypotensive therapy for medical reasons. Investigator assessments found optic disc parameters and visual field to be stable throughout 24 months of follow-up.

Efficacy, tolerability and satisfaction with sildenafil citrate 100-mg titration compared with continued 50-mg dose treatment in men with erectile dysfunction.

OBJECTIVE: To evaluate the efficacy, tolerability, and treatment satisfaction after initiating treatment with sildenafil 50 mg and later titrating to 100 mg, compared with continuing treatment with sildenafil 50 mg, in men with erectile dysfunction (ED). PATIENTS AND METHODS: A multicentre, parallel-group trial was conducted in two 4-week periods. In period 1, patients received 50-mg doses of sildenafil single-blinded for 4 weeks. In period 2, patients were randomized to double-blind, placebo-controlled treatment with sildenafil 50 mg or sildenafil 100 mg for 4 weeks. All patients were aged >or=18 years with a documented clinical diagnosis of ED (score of