Stephen J. Ruoss

A multiparameter wearable physiologic monitoring system for space and terrestrial applications

A novel, unobtrusive and wearable, multiparameter ambulatory physiologic monitoring system for space and terrestrial applications, termed LifeGuard, is presented. The core element is a wearable monitor, the crew physiologic observation device (CPOD), that provides the capability to continuously record two standard electrocardiogram leads, respiration rate via impedance plethysmography, heart rate, hemoglobin oxygen saturation, ambient or body temperature, three axes of acceleration, and blood pressure. These parameters can be digitally recorded with high fidelity over a 9-h period with precise time stamps and user-defined event markers. Data can be continuously streamed to a base station using a built-in Bluetooth RF link or stored in 32 MB of on-board flash memory and downloaded to a personal computer using a serial port. The device is powered by two AAA batteries. The design, laboratory, and field testing of the wearable monitors are described.

Tuberculosis in Liver Transplant Recipients: A Systematic Review and Meta-Analysis of Individual Patient Data

Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid‐related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short‐term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18‐fold increase in the prevalence of active MTB infection and a 4‐fold increase in the case‐fatality rate. For high‐risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894–906, 2009.

Aerosolized amikacin for treatment of pulmonary Mycobacterium avium infections: an observational case series.

BackgroundCurrent systemic therapy for nontuberculous mycobacterial pulmonary infection is limited by poor clinical response rates, drug toxicities and side effects. The addition of aerosolized amikacin to standard oral therapy for nontuberculous mycobacterial pulmonary infection may improve treatment efficacy without producing systemic toxicity. This study was undertaken to assess the safety, tolerability and preliminary clinical benefits of the addition of aerosolized amikacin to a standard macrolide-based oral treatment regimen.Case PresentationsSix HIV-negative patients with Mycobacterium avium intracellulare pulmonary infections who had failed standard therapy were administered aerosolized amikacin at 15 mg/kg daily in addition to standard multi-drug macrolide-based oral therapy. Patients were monitored clinically and serial sputum cultures were obtained to assess response to therapy. Symptomatic improvement with radiographic stabilization and eradication of mycobacterium from sputum were considered markers of success.Of the six patients treated with daily aerosolized amikacin, five responded to therapy. All of the responders achieved symptomatic improvement and four were sputum culture negative after 6 months of therapy. Two patients became re-infected with Mycobacterium avium intracellulare after 7 and 21 months of treatment. One of the responders who was initially diagnosed with Mycobacterium avium intracellulare became sputum culture positive for Mycobacterium chelonae resistant to amikacin after being on intermittent therapy for 4 years. One patient had progressive respiratory failure and died despite additional therapy. There was no evidence of nephrotoxicity or ototoxicity associated with therapy.ConclusionAerosolized delivery of amikacin is a promising adjunct to standard therapy for pulmonary nontuberculous mycobacterial infections. Larger prospective trials are needed to define its optimal role in therapy of this disease.

Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease

Rationale: Lengthy, multidrug, toxic, and low‐efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease. Objectives: In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment‐refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. Methods: During the double‐blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open‐label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6‐minute‐walk distance, and adverse events. Measurements and Main Results: The modified intention‐to‐treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double‐blind and open‐label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 [32%] of 44 vs. 4 [9%] of 45; P = 0.006) and improvement in 6‐minute‐walk test (+20.6 m vs. −25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation. Conclusions: Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6‐minute‐walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).

Diagnosing invasive fungal disease in critically ill patients

Fungal infections are increasing, with a changing landscape of pathogens and emergence of new groups at risk for invasive disease. We review current diagnostic techniques, focusing on studies in critically ill patients. Microbiological cultures, the current “gold standard”, demonstrate poor sensitivity, thus diagnosis of invasive disease in the critically ill is difficult. This diagnostic dilemma results in under- or over-treatment of patients, potentially contributing to poor outcomes and antifungal resistance. While other current diagnostic tests perform moderately well, many lack timeliness, efficacy, and are negatively affected by treatments common to critically ill patients. New nucleic acid-based research is promising.

A Dose–Response Study of Acetazolamide for Acute Mountain Sickness Prophylaxis in Vacationing Tourists at 12,000 Feet (3630 m)

The study objective was to determine whether acetazolamide is effective in prophylaxis of acute mountain sickness (AMS) at moderate altitude in ambulatory travelers not undergoing vigorous exercise. Volunteers vacationing in La Paz, Bolivia (3630 m), immediately after arrival from sea level were studied. The design was a double-blind, randomized trial of two doses of acetazolamide (125 mg twice daily, 250 mg twice daily) versus placebo twice daily over a 24-h period. The main outcome measure was AMS score and score trend, using the Lake Louise consensus questionnaire. Nine of 32 subjects (28%) had symptom scoring diagnostic of AMS at 0 h. At 0 and 24 h (respectively), the mean Lake Louise scores were 1.73 and 1.09 for the 11 subjects receiving placebo, 1.45 and 1.36 for the 11 subjects receiving the 125-mg dose, and 2.7 and 0.6 for the 11 subjects receiving the 250-mg dose. The absolute change in these mean scores was not significant for placebo (p = 0.21) or the 125-mg dose (p = 0.88), but was significant for the 250-mg dose (p = 0.008). A comparison of a difference in decline in average AMS score over time showed a statistically significant decline for the 250-mg dosing group versus placebo (p = 0.002). The 250-mg dose of acetazolamide twice daily (but not 125 mg twice daily) was effective in inducing a significant decline in AMS symptoms over the 24-h period after arrival to 3630 m. These results suggest that the dosing of acetazolamide for AMS prevention in nonmountaineering tourists at altitudes below 3700 m should not be lowered below 250 mg twice daily.

The International LAM Registry: A Component of an Innovative Web-Based Clinician, Researcher, and Patient-Driven Rare Disease Research Platform

BACKGROUND A relative inability to capture a sufficiently large patient population in any one geographic location has traditionally limited research into rare diseases. METHODS AND RESULTS Clinicians interested in the rare disease lymphangioleiomyomatosis (LAM) have worked with the LAM Treatment Alliance, the MIT Media Lab, and Clozure Associates to cooperate in the design of a state-of-the-art data coordination platform that can be used for clinical trials and other research focused on the global LAM patient population. This platform is a component of a set of web-based resources, including a patient self-report data portal, aimed at accelerating research in rare diseases in a rigorous fashion. CONCLUSIONS Collaboration between clinicians, researchers, advocacy groups, and patients can create essential community resource infrastructure to accelerate rare disease research. The International LAM Registry is an example of such an effort. 82.

Diaphragmatic paralysis due to Lyme disease

Lyme disease is a tick-borne spirochaete infection which, in a proportion of patients, can lead to neuropathy. This article describes a case of diaphragmatic paralysis due to Lyme disease. A 39-yr-old male presented to the hospital because of an acute left facial palsy. Six weeks prior to admission he had developed a circular rash on his left flank during a camping holiday. He also complained of shortness of breath and arthralgia for 1 week. His chest radiograph demonstrated a raised right hemi-diaphragm. Diaphragmatic paralysis was confirmed by fluoroscopy (a positive sniff test). Serology revealed evidence of recent infection by Borrelia burgdorferi. On the basis of the patients clinical presentation, a recent history of erythema migrans, and positive Lyme serology, a diagnosis of neuroborreliosis was made. He received oral doxycycline therapy (200 mg x day(-1)) for three weeks. Facial and diaphragmatic palsies resolved within eight weeks. On the basis of this case, a diagnosis of Lyme disease should be considered in patients from endemic regions with otherwise unexplained phrenic nerve palsy.

Coexistence of primary adenocarcinoma of the lung and Tsukamurella infection: a case report and review of the literature

IntroductionA major diagnostic challenge in the evaluation of a cavitary lung lesion is to distinguish between infectious and malignant etiologies.Case presentationWe present the case of an elderly man presenting with fever, hemoptysis and a left upper lobe cavitary lesion. Serial sputum cultures grew Tsukamurella pulmonis, a rare pathogen associated with cavitary pneumonia in immunocompromised patients. However, despite clinical improvement with antibiotic therapy targeted to the organism, concomitant discovery of a papillary thyroid carcinoma led to a needle biopsy of the cavitary lesion, which showed evidence of primary lung adenocarcinoma.ConclusionThis is the first description of Tsukamurella infection in the setting of primary lung carcinoma. The report also illustrates the potential complex nature of cavitary lesions and emphasizes the need to consider the coexistence of malignant and infectious processes in all patients, especially those with risk factors for malignancy that fail to improve on antibiotic therapy.

Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases

The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogeneous processes characterised by the presence of multiple, thin-walled, air-filled spaces within the pulmonary parenchyma [1]. The differential diagnosis of DCLDs includes lymphangioleiomyomatosis (LAM), follicular bronchiolitis (FB), lymphocytic interstitial pneumonia (LIP), Birt–Hogg–Dubé syndrome (BHD), pulmonary Langerhans cell histiocytosis (PLCH), amyloidosis, light chain deposition disease, cystic metastases, infectious entities such as Pneumocystis, and other aetiologies [2]. Bronchiectasis and bullous changes seen in chronic obstructive pulmonary disease can also produce high-resolution computed tomography (HRCT) patterns that mimic the DCLDs. Correct diagnosis of diffuse cystic lung diseases is established in most cases by critical review of HRCT features http://ow.ly/NvrCc