Abstract
Gladwin MT, Kato GJ, Weiner D, Onyekwere OC, Dampier C, Hsu L, Hagar RW, Howard T, Nuss R, Okam MM, Tremonti CK, Berman B, Villella A, Krishnamurti L, Lanzkron S, Castro O, Gordeuk VR, Coles WA, Peters-Lawrence M, Nichols J, Hall MK, Hildesheim M, Blackwelder WC, Baldassarre J, Casella JF; DeNOVO Investigators: Nitric Oxide for inhalation in the acute treatment of sickle cell pain crisis. A Randomized Controlled Trial. JAMA 2011;305:893–902.
Sickle cell disease (SCD) affects the beta globulin gene, precipitating occlusion of small blood vessels and manifesting clinically as episodes of severe pain known as vaso-occlusive crisis (VOC), damage to vital organs, and premature death. Inhaled nitric oxide has shown evidence of efficacy in mouse models of SCD, case series of patients with acute chest syndrome, and two small placebo-controlled trials for treatment of VOC. In this prospective, multicenter, double-blinded, randomized, placebo-controlled study, the authors attempted to determine whether inhaled nitric oxide gas for up to 72 hours (versus inhaled nitrogen placebo) reduces the duration of painful crisis in patients with SCD who present to the emergency department or hospital for care. One hundred fifty participants presenting with VOC of SCD at 11 centers between October 5, 2004, and December 22, 2008 were studied. The primary end point was the time to resolution of painful crisis, defined by (1) freedom from parenteral opioid use for 5 hours; (2) pain relief as assessed by visual analog pain scale scores of 6 or lower (on 0–10 scale); (3) ability to walk; and (4) patient's and family's decision, with physician consensus, that the remaining pain could be managed at home. Results demonstrated that there was no significant change in the primary end point between the nitric oxide and placebo groups, with a median time to resolution of crisis of 73 hours (95% confidence interval [CI], 46.0–91.0) and 65.5 hours (95% CI, 48.1–84.0), respectively (p = 0.87). There were also no significant differences in secondary outcome measures, including length of hospitalization, visual analog pain scale scores, cumulative opioid usage, and rate of acute chest syndrome. Inhaled nitric oxide was well tolerated, with no increase in serious adverse events. Increases in venous methemoglobin concentration confirmed adherence and randomization but did not exceed 5% in any study participant. Significant increases in plasma nitrate occurred in the treatment group, but there were no observed increases in plasma or whole blood nitrite. The authors conclude that among patients with SCD hospitalized with VOC, the use of inhaled nitric oxide compared with placebo did not improve time to crisis resolution.
Arslan C, Aksoy S, Dizdar O, Dede DS, Harputluoglu H, Altundag K: Zoledonic acid and atrial fibrillation in cancer patients. Support Care Cancer 2011;19:425–430.
Bisphosphonates are routinely used in cancer treatment. Treatment with a bisphosphonate was found to be associated with a significantly increased risk for atrial fibrillation (AF) in a few studies. A recent study showed that once-yearly infusions of intravenous zoledronic acid (ZA) significantly increased the risk of serious AF in postmenopausal women with osteoporosis. In this study, the authors attempted to determine the frequency of AF among cancer patients receiving the standard treatment of ZA. Patients with bone metastases who presented to the authors' outpatient clinic for any reason (routine control, chemotherapy, or ZA administration) were included in the study. All patients had been receiving 4 mg ZA at 4-week intervals, with each dose administered over 15 minutes. A short survey was completed and standard 12-lead ECG recordings were obtained. One hundred twenty-four patients with cancer with documented bone metastases were evaluated. Mean age of the patients was 55 ± 13.0 years, and 60% of the patients were female. Forty-one percent of the patients had breast cancer, 18% had non-small–cell lung cancer, and the remainder had other solid tumors. Mean duration of ZA administration was 13.4 ± 15.0 months. Mean total cumulative dose was 54 ± 15.0 mg per patient. Sixty patients (48%) had previously been treated with anthracycline-containing regimens, and 37 (30%) had received chest radiotherapy that might affect the heart. Twenty-three percent of the patients had hypertension, 10% had diabetes mellitus, 3.7% had a history of myocardial infarction, 1.9% had congestive heart failure, and 1% had valvular disease; 10.5% were current smokers and 32% ex-smokers. On ECG evaluation, the authors observed normal sinus rhythm in 58%, sinus tachycardia in 15%, sinus bradycardia in 3.2%, and ventricular extrasystoles in 5.7% of the patients. There was no atrial fibrillation in any of the cases. The authors conclude that there was no increase in the risk of atrial fibrillation frequency in patients with cancer who were treated with intravenous ZA, although most of the patients had additional risk factors including previous treatment with cardiotoxic agents or with chest radiotherapy. The authors believe that the risk of AF is negligible in this patient population and does not affect treatment decisions.
Luo H, Lin M, Castle N: Physical restraint use and falls in nursing homes: A comparison between residents with and without dementia. Am J Alz Dis Dementias 2011;26:44–50.
Alzheimer's disease in increasing with an aging population. Unfortunately, many Alzheimer's patients spend the final weeks, months, and years of their lives in a nursing home. In this study, the authors attempted to estimate the use of different types of physical restraints and assess their associations to falls and injuries among residents with and without Alzheimer's disease (AD) or dementia in U.S. nursing homes. Data used in the study were from the 2004 National Nursing Home Survey. AD or dementia was identified using International Classification of Diseases, Ninth Revision (ICD-9) codes. Analyses were conducted with the Surveyfreq and Surveylogistic procedures in SAS v.9.1. Results demonstrated that residents with either AD or dementia were more likely to be physically restrained (9.99% versus 3.91%, p < 0.001) and less likely to have bed rails (35.06% versus 38.43%, p < 0.001) than those residents without the disease. The use of trunk restraints was associated with higher risk for falls (adjusted odds ratio [AOR] ¼ 1.66, p < 0.001) and fractures (AOR ¼ 2.77, p < 0.01) among residents with the disease. The use of full bed rails was associated with lower risk for falls among residents with and without the disease (AOR ¼ 0.67 and AOR ¼ 0.72, p < 0.05, respectively). The authors conclude that the use of a trunk restraint is associated with a higher risk for falls and fractures among residents with either AD or dementia.
Ben-Ayre E, Schiff E, Steiner M, Silberman M: Wheatgrass in Afifi's garden: Sprouting integrative oncology collaborations in the Middle East. J Clin Oncol 2011;29:944–946.
In this brief article (one in a series from the valuable series titled The Art of Oncology) regarding integrative therapies in cancer care, the authors provide a case report from Israel of a woman with locally advanced gastric cancer with significant side effects from her cancer and chemotherapy who requests the use of integrative therapy (specifically medicinal herbs). The article reminds us of the value and use of integrative therapies in cancer patients, and is interesting reading.
McNeely ML, Peddle CJ, Yurick JL, Dayes IS, Mackey JR: Conservative and dietary interventions for cancer-related lymphedema. A systematic review and meta-analysis. Cancer 2011; 117:1136–1148.
Lymphedema remains a prevalent and potentially debilitating side effect of cancer treatment. Although data on the prevalence of lymphedema are limited, it is estimated that over 3 million people in the United States suffer from lymphedema, with a significant proportion developing the disease secondary to cancer and/or cancer treatment. When treated conservatively in the earliest stages, complications of lymphedema may be diminished or reversed. Unfortunately, lymphedema may progress to irreversible swelling and fibrosis requiring lifelong attention and management. Thus, the impact of chronic lymphedema for the cancer survivor is often profound, resulting in significant psychosocial morbidity and poorer quality of life. In this review, the authors searched the following electronic databases from January 1980 to August 2009: MEDLINE, PubMed, EMBASE, CINAHL, Dissertation Abstracts, PEDro, and EBM Reviews (Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews). The authors identified 157 articles, of which 48 were considered potentially relevant. Independent review of these 48 articles led to the inclusion of 25 studies involving 1018 participants. The authors report that the findings support the use of compression garments and compression bandaging for reducing lymphedema volume in upper and lower extremity cancer-related lymphedema. Specific to breast cancer, a statistically significant, clinically small beneficial effect was found from the addition of manual lymph drainage massage to compression therapy for upper extremity lymphedema volume.