Publications

Health disparities are prevalent across diseases of the respiratory system, and are major sources of morbidity and mortality among disadvantaged populations in the United States. The American Thoracic Society (ATS) aims to reduce disparities that are both avoidable and unjust. In meeting this goal, the ATS is committed to creating the Lung Corps, a diverse group of senior, mid-level, and junior clinicians, trainees, researchers, and public health practitioners to help achieve health equality. This will be achieved through the following mechanisms: (1) increase awareness of health disparities; (2) empower health professionals with the knowledge and tools to address disparities; (3) shape research agendas to focus on the root causes, to identify modifiable targets, and to promote innovative approaches to reduce disparities; and (4) develop and advocate for health-related policies and regulations that improve the respiratory health of the population. To ensure success, the Lung Corps will interact with other societies, agencies, and organizations to effect elimination of disparities in respiratory health. The ATS is committed to identifying and addressing health disparities to improve the overall health of individuals affected by respiratory diseases.

Prostate cancer has surpassed lung cancer as the most common cancer in men in the United States. The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer based on clinical evidence and expert consensus. NCCN Panel guidance on treatment decisions for patients with localized disease is represented in this version. Significant updates for early disease include distinction between active surveillance and observation, a new section on principles of imaging, and revisions to radiation recommendations. The full version of these guidelines, including treatment of patients with advanced disease, can be found online at the NCCN website.

Neuroendocrine prostate cancer (NEPC) encompasses various clinical contexts, ranging from the de novo presentation of small cell prostatic carcinoma to a treatment-emergent transformed phenotype that arises from typical adenocarcinoma of the prostate. The development of resistance to potent androgen receptor signaling inhibition may be associated with the emergence of aggressive phenotype, advanced castration-resistant NEPC. Clinically, small cell prostate cancer and NEPC are often manifested by the presence of visceral or large soft tissue metastatic disease, a disproportionately low serum prostate-specific antigen level relative to the overall burden of disease, and a limited response to targeting of the androgen signaling axis. These tumors are often characterized by loss of androgen receptor expression, loss of retinoblastoma tumor suppressor copy number or expression, amplification of Aurora kinase A and N-Myc, and activation of the PI3K pathway. However, a consensus phenotype-genotype definition of NEPC has yet to emerge, and molecularly based biomarkers are needed to expand on traditional morphologic and immunohistochemical markers of NEPC to fully define the spectrum of this aggressive, androgen receptor-independent disease. Emerging studies implicate a shared clonal origin with prostatic adenocarcinoma in many cases, with the adaptive emergence of unique cellular programming and gene expression profiles. Ongoing clinical studies are focused on developing novel targeted therapeutic approaches for this high-risk, lethal subset of disease, to improve on the limited durations of response often observed with traditional platinum-based chemotherapy.

IMPORTANCE

Surgery in older patients often poses risks of death, complications, and functional decline. Prior to surgery, evaluations of health-related priorities, realistic assessments of surgical risks, and individualized optimization strategies are essential.

OBJECTIVE

To review surgical decision making for older adult patients by 2 measures: defining treatment goals for elderly patients and reviewing the evidence relating risk factors to adverse outcomes. Assessment and optimization strategies for older surgical patients are proposed.

EVIDENCE ACQUISITION

A review of studies relating geriatric conditions such as functional and cognitive impairment, malnutrition, facility residence, and frailty to postoperative mortality and complications (including delirium, discharge to an institution, and functional decline). Medline, EMBASE, and Web of Science databases were searched for articles published between January 1, 2000, and December 31, 2013, that included patients older than 60 years.

RESULTS

This review identified 54 studies of older patients; 28 that examined preoperative clinical features associated with mortality (n = 1,422,433 patients) and 26 that examined factors associated with surgical complications (n = 136,083 patients). There was substantial heterogeneity in study methods, measures, and outcomes. The absolute risk and risk ratios relating preoperative clinical conditions to mortality varied widely: 10% to 40% for cognitive impairment (adjusted hazard ratio [HR], 1.26 [95% CI, 1.06-1.49] to 5.77 [95% CI, 1.55-21.55]), 10% to 17% for malnutrition (adjusted odds ratio [OR], 0.88 [95% CI, 0.78-1.01] to 59.2 [95% CI, 3.6-982.9]), and 11% to 41% for institutionalization (adjusted OR, 1.5 [95% CI, 1.02-2.21] to 3.27 [95% CI, 2.81-3.81]).) Risk ratios for functional dependence relating to mortality ranged from an adjusted HR of 1.02 (95% CI, 0.99-1.04) to an adjusted OR of 18.7 (95% CI, 1.6-215.3) and for frailty relating to mortality, ranged from an adjusted HR of 1.10 (95% CI, 1.04-1.16) to an adjusted OR of 11.7 (95% CI not reported) (P < .001). Preoperative cognitive impairment (adjusted OR, 2.2; 95% CI, 1.4-2.7) was associated with postoperative delirium (adjusted OR, 17.0; 95% CI, 1.2-239.8; P < .05). Frailty was associated with a 3- to 13-fold increased risk of discharge to a facility (adjusted OR, 3.16 [95% CI, 1.0-9.99] to 13.02 [95% CI, 5.14-32.98]).

CONCLUSIONS AND RELEVANCE

Geriatric conditions may be associated with adverse surgical outcomes. A comprehensive evaluation of treatment goals and communication of realistic risk estimates are essential to guide individualized decision making.

IMPORTANCE

In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.

OBJECTIVE

To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.

DESIGN, SETTING, AND PARTICIPANTS

The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.

INTERVENTIONS

Oral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained.

MAIN OUTCOMES AND MEASURES

The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).

RESULTS

Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]).

CONCLUSIONS AND RELEVANCE

Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01248065.