Patient considerations in the treatment of COPD: focus on the new combination inhaler umeclidinium/vilanterol.

Medication adherence among patients with chronic diseases, such as COPD, may be suboptimal, and many factors contribute to this poor adherence. One major factor is the frequency of medication dosing. Once-daily dosing has been shown to be an important variable in medication adherence in chronic diseases, such as COPD. New inhalers that only require once-daily dosing are becoming more widely available. Combination once-daily inhalers that combine any two of the following three agents are now available: 1) a long-acting muscarinic antagonist; 2) a long acting beta2 agonist; and 3) an inhaled corticosteroid. A new once-daily inhaler with both a long-acting muscarinic antagonist, umeclidinium bromide, and a long acting beta2 agonist, vilanterol trifenatate, is now available worldwide for COPD treatment. It provides COPD patients convenience, efficacy, and a very favorable adverse-effects profile. Additional once-daily combination inhalers are available or will soon be available for COPD patients worldwide. The use of once-daily combination inhalers will likely become the standard maintenance management approach in the treatment of COPD because they improve medication adherence

Clinical review: Update of avian influenza A infections in humans

Influenza A viruses have a wide host range for infection, from wild waterfowl to poultry to humans. Recently, the cross-species transmission of avian influenza A, particularly subtype H5N1, has highlighted the importance of the non-human subtypes and their incidence in the human population has increased over the past decade. During cross-species transmission, human disease can range from the asymptomatic to mild conjunctivitis to fulminant pneumonia and death. With these cases, however, the risk for genetic change and development of a novel virus increases, heightening the need for public health and hospital measures. This review discusses the epidemiology, host range, human disease, outcome, treatment, and prevention of cross-transmission of avian influenza A into humans

The value of a risk model for early-onset candidemia

Bloodstream infections from Candida species are associated with an increased length of stay, increased hospital costs, and higher mortality when compared with bacterial bloodstream infections. Delayed or inappropriate therapy in candidemia leads to increased mortality, thus early recognition becomes paramount. With biomarkers showing promise, blood cultures still remain the gold standard but require 24 to 72 hours for growth. The reliance on epidemiologic risk factors for the initiation of empiric antifungal therapy therefore provides the best method for early appropriate therapy. Shorr and colleagues have devised a risk score to identify patients with early-onset candidemia as defined by positive blood cultures within 2 days of admission, thus allowing for the initiation of early appropriate antifungal therapy

Bench-to-bedside review: Rare and common viral infections in the intensive care unit – linking pathophysiology to clinical presentation

Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus

Contribution of Different Scintigraphic Techniques to the Management of Medullary Thyroid Carcinoma

We compared three differenl scintigraphic techniques for the localization of neck recurrences and metastases in seven patients wiih medullary thyroid carcinoma one month to eight years after the first surgical intervention. Three successive scintigraphic studies were performed in five patients (6x3 studies) within two weeks using 201Tl chloride, 111In-labeled F(ab\u27)2 fragments of the anticarcinoembryonic antigen (anti-CEA) monoclonal antibody (MoAb) BW 431/31. and 131I meta-iodobenzylguanidine (MIBG). Additionally, 11 studies were performed wilh the 111In-labeled MoAb fragment BW 431/31 (seven studies) or the 99mTc-labeled intact anti-CEA MoAb BW 431/26 (four studies). The gold standards for classifying scintigraphic results were biopsy, histology, surgery, and cytology. Six regions were classified as positive or negalive in each study: thyroid region, four quadrants (lymph node regions) around the thyroid, and the region of the upper mediastinum. Of 36 sites, 201Tl was true positive (TP) in seven sites, false-positive (FP) in one site, true negative (TN) in 22 sites, and false-negative (FN) in six sites, resulting in a sensitivity of 54% and a specificity of 96%. 131I MIBG was TP in four sites, FP in none of the sites, TN in 23 sites, and FN in nine sites, with a sensitivity of 31% and a specificity of 100%. Immunoscintigraphy (102 sites overall) was TP in 16 sites, FP in five sites, TN in 77 siles, and FN in four siles. resulting in a sensitivity of 80% and a specificity of 94%. Immunoscintigraphy with 111In/99mTc anti-CEA F(ab\u27)2 fragment/intact antibody is superior to scintigraphy with 201Tl and 131I MIBG

Exercises in Emergency Preparedness for Health Professionals in Community Clinics

Health professionals in community settings are generally unprepared for disasters. From 2006 to 2008 the California Statewide Area Health Education Center (AHEC) program conducted 90 table top exercises in community practice sites in 18 counties. The exercises arranged and facilitated by AHEC trained local coordinators and trainers were designed to assist health professionals in developing and applying their practice site emergency plans using simulated events about pandemic influenza or other emergencies. Of the 1,496 multidisciplinary health professionals and staff participating in the exercises, 1,176 (79%) completed learner evaluation forms with 92–98% of participants rating the training experiences as good to excellent. A few reported helpful effects when applying their training to a real time local disaster. Assessments of the status of clinic emergency plans using 15 criteria were conducted at three intervals: when the exercises were scheduled, immediately before the exercises, and for one-third of sites, three months after the exercise. All sites made improvements in their emergency plans with some or all of the plan criteria. Of the sites having follow up, most (N = 23) were community health centers that made statistically significant changes in two-thirds of the plan criteria (P = .001–.046). Following the exercises, after action reports were completed for 88 sites and noted strengths, weaknesses, and plans for improvements in their emergency plans Most sites (72–90%) showed improvements in how to activate their plans, the roles of their staff, and how to participate in a coordinated response. Challenges in scheduling exercises included time constraints and lack of resources among busy health professionals. Technical assistance and considerations of clinic schedules mitigated these issues. The multidisciplinary table top exercises proved to be an effective means to develop or improve clinic emergency plans and enhance the dialogue and coordination among health professionals before an emergency happens

Risk for Avian Influenza Virus Exposure at Human–Wildlife Interface

To assess risk for human exposure to avian influenza viruses (AIV), we sampled California wild birds and marine mammals during October 2005–August 2007and estimated human–wildlife contact. Waterfowl hunters were 8 times more likely to have contact with AIV-infected wildlife than were persons with casual or occupational exposures (p<0.0001)

A fetal wave of human type 3 effector gamma delta cells with restricted TCR diversity persists into adulthood

Accumulating evidence suggests that the mouse embryonic thymus produces distinct waves of innate effector gamma delta T cells. However, it is unclear whether this process occurs similarly in humans and whether it comprises a dedicated subset of innate-like type 3 effector gamma delta T cells. Here, we present a protocol for high-throughput sequencing of TRG and TRD pairs that comprise the clonal gamma delta TCR. In combination with single-cell RNA sequencing, multiparameter flow cytometry, and TCR sequencing, we reveal a high heterogeneity of gamma delta T cells sorted from neonatal and adult blood that correlated with TCR usage. Immature gamma delta T cell clusters displayed mixed and diverse TCRs, but effector cell types segregated according to the expression of either highly expanded individual V delta 1(+) TCRs or moderately expanded semi-invariant V gamma 9V delta 2(+) TCRs. The V gamma 9V delta 2(+) T cells shared expression of genes that mark innate-like T cells, including ZBTB16 (encoding PLZF), KLRB1, and KLRC1, but consisted of distinct clusters with unrelated V gamma 9V delta 2(+) TCR clones characterized either by TBX21, FCGR3A, and cytotoxicity-associated gene expression (type 1) or by CCR6, RORC, IL23R, and DPP4 expression (type 3). Effector gamma delta T cells with type 1 and type 3 innate T cell signatures were detected in a public dataset of early embryonic thymus organogenesis. Together, this study suggests that functionally distinct waves of human innate-like effector gamma delta T cells with semi-invariant V gamma 9V delta 2(+) TCR develop in the early fetal thymus and persist into adulthood

Functional Comparison of Induced Pluripotent Stem Cell- and Blood-Derived GPIIbIIIa Deficient Platelets

Human induced pluripotent stem cells (hiPSCs) represent a versatile tool to model genetic diseases and are a potential source for cell transfusion therapies. However, it remains elusive to which extent patient-specific hiPSC-derived cells functionally resemble their native counterparts. Here, we generated a hiPSC model of the primary platelet disease Glanzmann thrombasthenia (GT), characterized by dysfunction of the integrin receptor GPIIbIIIa, and compared side-by-side healthy and diseased hiPSC-derived platelets with peripheral blood platelets. Both GT-hiPSC-derived platelets and their peripheral blood equivalents showed absence of membrane expression of GPIIbIIIa, a reduction of PAC-1 binding, surface spreading and adherence to fibrinogen. We demonstrated that GT-hiPSC-derived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSC-based disease models as well as the transition towards a clinical application

Implementing Telemedicine in Medical Emergency Response: Concept of Operation for a Regional Telemedicine Hub

A regional telemedicine hub, providing linkage of a telemedicine command center with an extended network of clinical experts in the setting of a natural or intentional disaster, may facilitate future disaster response and improve patient outcomes. However, the health benefits derived from the use of telemedicine in disaster response have not been quantitatively analyzed. In this paper, we present a general model of the application of telemedicine to disaster response and evaluate a concept of operations for a regional telemedicine hub, which would create distributed surge capacity using regional telemedicine networks connecting available healthcare and telemedicine infrastructures to external expertise. Specifically, we investigate (1) the scope of potential use of telemedicine in disaster response; (2) the operational characteristics of a regional telemedicine hub using a new discrete-event simulation model of an earthquake scenario; and (3) the benefit that the affected population may gain from a coordinated regional telemedicine network