Physiologic implications of helium as a carrier gas for inhaled nitric oxide in a neonatal model of Bethanecol-induced bronchoconstriction.

OBJECTIVE: To compare heliox to nitrogen-oxygen (nitrox) as a carrier gas for inducible nitric oxide (iNO) in the presence of pharmacologically inhaled bronchoconstriction. We hypothesized that respiratory resistance and gas exchange would improve when iNO is delivered with heliox. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in the northeastern United States. SUBJECTS: Sedated, ventilated newborn piglets. INTERVENTIONS: Newborn piglets (n = 16; 2.3 +/- 0.1 kg) were placed on a flow-controlled ventilator and given intravenous Bethanecol (2 x 1 mg/kg followed by 1 mg/kg/hr) to induce bronchoconstriction. Piglets were randomized to heliox or nitrox (Fio2 = 0.3) and given 80 ppm iNO. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, blood chemistry, and pulmonary mechanics were recorded at 30-min intervals for 2 hrs. Bethanecol dosing increased inspiratory respiratory resistance (cm H2O/L/min; p < .01) and decreased respiratory compliance (mL/cm H2O/kg; p < .01). Following carrier gas assignment, hemodynamics and respiratory compliance were similar between groups and respiratory resistance decreased (p < .01) in the heliox group. Over 2 hrs with iNO therapy, Paco2 increased (p < .01) whereas blood pH decreased (p < .01) in the heliox group. Respiratory resistance trended downward, oxygenation index improved (p < .01), and blood methemoglobin levels trended higher for nitrox compared with heliox. CONCLUSIONS: The INOvent was effective for controlling heliox delivery of iNO. Despite marked reduction in respiratory resistance with heliox gas ventilation in a neonatal model of pharmacologic bronchoconstriction, nitrox might perform better as a delivery vehicle for iNO.     

A placebo controlled, double-blind study of mecamylamine treatment for cocaine dependence in patients enrolled in an opiate replacement program.

A placebo controlled, double-blind trial of mecamylamine treatment of cocaine dependence was performed in methadone or LAAM maintained subjects who met DSM-IV criteria for cocaine dependence. After an eight-week placebo run-in screening period, 35 subjects were randomly assigned to receive either mecamylamine (6 mg/day) or placebo transdermal patches for a 16-week treatment period. Outcome measures included quantitative urine benzoylecognine (BE) levels, self-report of cocaine use, cocaine craving, global impression scores, mood, retention, and safety. Mecamylamine was well tolerated, and study retention did not differ by treatment group. Evidence for cocaine use, based on urine BE levels and cocaine abstinence rates, did not differ by treatment group. Self reported cocaine use, cocaine craving, and global impression scores showed moderate improvement in both groups, with a significantly greater reduction in cocaine craving (p < 0.05) and self-rated severity of cocaine dependence (p < 0.05) in the placebo group. This pilot study does not support the effectiveness of mecamylamine for the treatment of cocaine dependence in methadone or LAAM maintained patients.     

Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.

PURPOSE: Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. PATIENTS AND METHODS: During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). RESULTS: Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. CONCLUSION: These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.     

Rebasing the Medicare Payment for Dialysis: Rationale,Challenges, and Opportunities

After Medicare’s implementation of the bundled payment for dialysis in 2011, there has been a predictable decrease in the use of intravenous drugs included in the bundle. The change in use of erythropoiesis-stimulating agents, which decreased by 37% between 2007, when its allowance in the bundle was calculated, and 2012, was because of both changes in the Food and Drug Administration labeling for erythropoiesis-stimulating agents in 2011 and cost-containment efforts at the facility level. Legislation in 2012 required Medicare to decrease (rebase) the bundled payment for dialysis in 2014 to reflect this decrease in intravenous drug use, which amounted to a cut of 12% or $30 per treatment. Medicare subsequently decided to phase in this decrease in payment over several years to offset the increase in dialysis payment that would otherwise have occurred with inflation. A 3% reduction from the rebasing would offset an approximately 3% increase in the market basket that determines a facility’s costs for 2014 and 2015. Legislation in March of 2014 provides that the rebasing will result in a 1.25% decrease in the market basket adjustment in 2016 and 2017 and a 1% decrease in the market basket adjustment in 2018 for an aggregate rebasing of 9.5% spread over 5 years. Adjusting to this payment decrease in inflation-adjusted dollars will be challenging for many dialysis providers in an industry that operates at an average 3%–4% margin. Closure of facilities, decreases in services, and increased consolidation of the industry are possible scenarios. Newer models of reimbursement, such as ESRD seamless care organizations, offer dialysis providers the opportunity to align incentives between themselves, nephrologists, hospitals, and other health care providers, potentially improving outcomes and saving money, which will be shared between Medicare and the participating providers.     

Risk factors for the development of acute lung injury in patients with infectious pneumonia

ABSTRACT: INTRODUCTION: Although pneumonia has been identified as the single most common risk factor for acute lung injury (ALI), we have a limited knowledge as to why ALI develops in some patients with pneumonia and not in others. The objective of this study was to determine frequency, risk factors, and outcome of ALI in patients with infectious pneumonia. METHODS: A retrospective cohort study of adult patients with microbiologically positive pneumonia, hospitalized at two Mayo Clinic Rochester hospitals between January 1, 2005, and December 31, 2007. In a subsequent nested case-control analysis, we evaluated the differences in prehospital and intrahospital exposures between patients with and without ALI/acute respiratory distress syndrome (ARDS) matched by specific pathogen, isolation site, gender, and closest age in a 1:1 manner. RESULTS: The study included 596 patients; 365 (61.2%) were men. The median age was 65 (IQR, 53 to 75) years. In total, 171 patients (28.7%) were diagnosed with ALI. The occurrence of ALI was less frequent in bacterial (n = 99 of 412, 24%) compared with viral (n = 19 of 55, 35%), fungal (n = 39 of 95, 41%), and mixed isolates pneumonias (n = 14 of 34, 41%; P = 0.002). After adjusting for baseline severity of illness and comorbidities, patients in whom ALI developed had a markedly increased risk of hospital death (ORadj 9.7; 95% CI, 6.0 to 15.9). In a nested case-control study, presence of shock (OR, 8.9; 95% CI, 2.8 to 45.9), inappropriate initial antimicrobial treatment (OR, 3.2; 95% CI, 1.3 to 8.5), and transfusions (OR, 4.8; 95% CI, 1.5 to 19.6) independently predicted ALI development. CONCLUSIONS: The development of ALI among patients hospitalized with infectious pneumonia varied among pulmonary pathogens and was associated with increased mortality. Inappropriate initial antimicrobial treatment and transfusion predict the development of ALI independent of pathogen.     

Increased incidence of bladder cancer,lymphoid leukaemia,and myeloma in a cohort of Queensland melanoma families

Familial cancer risk has been proposed as a shared feature of many cancers, and overall susceptibility is influenced by combinations of low to moderate risk polymorphisms, rare high penetrance germline mutations, and modulation of risk by environmental and genetic factors. Clustering of melanoma occurs in approximately 10 % of families, and an over-representation of additional cancers has been noticed in some ‘melanoma’ families. The degree to which other cancers aggregate in families affected by melanoma has not been well defined. Therefore, this study aimed to assess the risk of cancers other than melanoma in a cohort of 178 ‘intermediate risk’ melanoma families, not selected for specific genetic mutations. Families designated as ‘intermediate risk’ had two first degree relatives (FDRs) affected by melanoma when ascertained between 1982 and 1990, and were followed up over a 33 year period to assess new occurrences of cancer. We included 414 melanoma cases and 529 FDRs, comprising 25,264 person years of observation. Standardised incidence ratios and their 95 % confidence intervals were calculated for all invasive cancers, comparing observed to expected cases of cancer based on age and sex specific incidence rates for the Queensland population. Statistically significant increases were found for bladder cancer in females (observed, 7; expected, 1.99; SIR, 3.52; 95 % CI 1.41–7.25), lymphoid leukaemia in females (observed, 6; expected, 1.75; SIR, 3.43; 95 % CI 1.26–7.46), and myeloma in female melanoma cases (observed, 4; expected, 0.82; SIR, 4.89; 95 % CI 1.33–12.52). Over-representation of bladder cancer, lymphoid leukaemia, and myeloma in females of the cohort may suggest sex-dependent co-modifiers, and it is possible that specific combinations of polymorphisms predispose to certain cancer types.     

Treatment of submassive and massive pulmonary embolism: a clinical practice survey from the second annual meeting of the Pulmonary Embolism Response Team Consortium

There is a paucity of robust clinical trial data to guide the treatment of acute pulmonary embolism (PE) thus the clinical guidelines rely heavily on expert opinion. Pulmonary Embolism Response Teams (PERT) have been developed to streamline the care of patients with acute PE. We conducted a survey among 100 experts in the field of PE during the second annual meeting of the PERT Consortium. Respondents were queried with respect to their demographic information, clinical practice questions and clinical vignettes. Clinical practice questions were focused questions about the risk stratification and treatment of patients with acute submassive PE, anticoagulation strategies for patients receiving thrombolysis and the use of inferior vena cava filters. Clinical vignettes were designed to assess participants’ preferred choice of treatment for a variety of commonly encountered clinical scenarios. Among physicians affiliated with a PERT, there is overall agreement with regards to the criteria used for risk classification of patients with PE and its application to patients in the provided clinical vignettes. In contrast, there is substantial variability in the treatment strategies of patients presenting with commonly encountered clinical scenarios. The results of this survey highlight the need for more clinical trial data along with accepted algorithms for treatment of acute PE. In the absence of this, PERTs can facilitate multidisciplinary discussions in order to standardize treatment and provide evidence-based therapies to patients with acute PE.