Management and prevention strategies for respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a review of evidence-based practice interventions

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia among infants and children. The purpose of this paper is to review the epidemiology, etiology, pathophysiology, clinical manifestations, risk factors, and assessment of RSV infection in infants and young children. There is a lack of consensus regarding the optimal treatment for children with RSV infection. Bronchodilators, racemic epinephrine, inhaled and systemic corticosteroids, RSV-immunoglobulin (RSV-IG), and ribavirin have all been used for treatment of children with RSV infection. A review of current research indicates supportive and symptomatic management should be the mainstay of treatment. Ultimately, prevention of infection through education and immunotherapy is the key to reducing the morbidity and mortality associated with RSV bronchiolitis.     

DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells

Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mphis), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis-derived material was detected in CD14(-)HLA-DR(+)DC-SIGN(+) cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN-mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity.     

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden

Patients with inflammatory bowel disease have an increased frequency of thromboembolism, and microvascular thrombosis has been proposed as a contributory pathogenic factor. The mechanism of enhanced procoagulant activity is not understood. We examined the clinical setting of thromboembolic events in 52 patients with Crohn's disease or ulcerative colitis, and assessed the procoagulant laboratory profile, including Factor V Leiden, in a subset of 20 patients to identify procoagulant risk factors. Patients who developed thrombosis tended to be young; 60% of thrombotic events occurred in patients under 50 years. Multiple thromboembolic episodes occurred in 13% and unusual sites of thrombosis (e.g. intracardiac, cerebral, inominate veins) in 11%. No risk factor was identifiable in 52% of cases and two-thirds of thromboses occurred in an out-patient setting. The mortality rate was 8%. Evidence for inflammatory disease activity was found in only 45% of patients with ulcerative colitis at the time of the thromboembolic event, in contrast to 89% of those with Crohn's disease. Assays for specific coagulation defects were negative in all cases tested (protein S, C were normal in 17/17; anti-thrombin III, anti-phospholipid antibodies and activated protein C resistance were negative in 20/20, and only 1/20 patients was found to be heterozygous for Factor V leiden. Thrombosis in inflammatory bowel disease is important because it occurs in a young population, often in unusual sites, and has a high mortality. The development of thrombosis is related to active inflammatory disease in most patients with Crohn's disease but apparently not in those with ulcerative colitis. Since approximately half of the patients had no other identifiable risk factor, there remains a substantial group of patients with IBD who develop thrombosis for unknown reasons.      

75 MHz ultrasound biomicroscopy of anterior segment of eye

Very high frequency ultrasound (35-50 MHz) has had a significant impact upon clinical imaging of the anterior segment of the eye, offering an axial resolution as small as 30 microm. Higher frequencies, while potentially offering even finer resolution, are more affected by absorption in ocular tissues and even in the fluid coupling medium. Our aim was to develop and apply improved transducer technology utilizing frequencies beyond those routinely used for ultrasound biomicroscopy of the eye. A 75-MHz lithium niobate transducer with 2 mm aperture and 6 mm focal length was fabricated. We scanned the ciliary body and cornea of a human eye six years post-LASIK. Spectral parameter images were produced from the midband fit to local calibrated power spectra. Images were compared with those produced using a 35 MHz lithium niobate transducer of similar fractional bandwidth and focal ratio. The 75-MHz transducer was found to have a fractional bandwidth (-6 dB) of 61%. Images of the post-LASIK cornea showed higher stromal backscatter at 75 MHz than at 35 MHz. The improved lateral resolution resulted in better visualization of discontinuities in Bowman's layer, indicative of microfolds or breaks occurring at the time of surgery. The LASIK surface was evident as a discontinuity in stromal backscatter between the stromal component of the flap and the residual stroma. The iris and ciliary body were visualized despite attenuation by the overlying sclera. Very high frequency ultrasound imaging of the anterior segment of the eye has been restricted to the 35-50 MHz band for over a decade. We showed that higher frequencies can be used in vivo to image the cornea and anterior segment. This improvement in resolution and high sensitivity to backscatter from the corneal stroma will provide benefits in clinical diagnostic imaging of the anterior segment.     

Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1

We determined the prevalence of antibody to cytomegalovirus (CMV) in the sera of non-homosexual hemophilia patients and homosexual men infected with the human immunodeficiency virus type 1 (HIV-1). CMV antibody testing by latex agglutination revealed 33 of 58 HIV-1 infected hemophiliacs (57%) were antibody-positive compared with 54 of 54 HIV-1 infected asymptomatic non-hemophiliac homosexuals (100%) (p less than .001). Nine of 15 hemophiliacs (60%) with symptomatic HIV-1 infection were CMV antibody-positive. We also tested 22 HIV-1 antibody-negative hemophiliacs who had received non-heat treated factor concentrates. 14 of these 22 (64%) were CMV antibody-positive compared with 57% of HIV-1 antibody-positive hemophiliacs. We conclude 1) there is little correlation between transmission of HIV-1 and CMV by factor concentrates, 2) the presence of CMV antibody does not appear to be associated with clinical stage of HIV-1 infection in hemophiliacs, and 3) there may be a significant number of CMV antibody-negative hemophiliacs with HIV-1 infection at risk for primary infection and subsequent disease if CMV seronegative blood products are not provided for future transfusions.     

Development of an integrated care pathway for the management of hemiplegic shoulder pain

Purpose: To improve clinical management of patients with hemiplegic shoulder pain through development of an evidence-based multidisciplinary integrated care pathway (ICP), and to use this to audit quality of care against predefined standards. Methods: The ICP was developed by a team of medical, paramedical and nursing staff. The evidence base was established through a systematic literature review supplemented by clinical consensus to ensure best practice where scientific evidence was lacking. Following development, performance was assessed against standards in a cohort of stroke patients with hemiplegia (n=32) consecutively admitted to a regional unit providing in-patient rehabilitation for young patients with complex disabilities. Results: Performance showed improvements in assessment and documentation of pain and in initial care, including analgesia and application of positioning/handling protocols. However, review and response to continuing or changing symptoms were poorly documented. Changes to the ICP were introduced to improve this. Conclusions: Principal benefits have been to raise awareness of shoulder pain, to educate staff and prompt management in line with recommended best practice, but strong leadership is essential to ensure continuity in clinical practice. Future research is needed to establish whether improved quality of care offsets the substantial investment of staff time in ICP development.     

Remote FEV1 Monitoring in Asthma Patients: A Pilot Study

Forced expiratory volume in one second (FEV₁) is a critical parameter for the assessment of lung function for both clinical care and research in patients with asthma. While asthma is defined by variable airflow obstruction, FEV₁ is typically assessed during clinic visits. Mobile spirometry (mSpirometry) allows more frequent measurements of FEV₁, resulting in a more continuous assessment of lung function over time and its variability. Twelve patients with moderate asthma were recruited in a single‐center study and were instructed to perform pulmonary function tests at home twice daily for 28 days and weekly in the clinic. Daily and mean subject compliances were summarized. The agreement between clinic and mobile FEV₁ was assessed using correlation and Bland‐Altman analyses. The test‐retest reliability for clinic and mSpirometry was assessed by interclass correlation coefficient (ICC). Simulation was conducted to explore if mSpirometry could improve statistical power over clinic counterparts. The mean subject compliance with mSpirometry was 70% for twice‐daily and 85% for at least once‐daily. The mSpirometry FEV₁ were highly correlated and agreed with clinic ones from the same morning (r = 0.993) and the same afternoon (r = 0.988) with smaller mean difference for the afternoon (0.0019 L) than morning (0.0126 L) measurements. The test‐retest reliability of mobile (ICC = 0.932) and clinic (ICC = 0.942) spirometry were comparable. Our simulation analysis indicated greater power using dense mSpirometry than sparse clinic measurements. Overall, we have demonstrated good compliance for repeated at‐home mSpirometry, high agreement and comparable test‐retest reliability with clinic counterparts, greater statistical power, suggesting a potential for use in asthma clinical research.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

☑ Forced expiratory volume in one second (FEV1) is the gold standard in clinical care and research practice for assessing patients with asthma. Mobile spirometry (mSpirometry) provides an opportunity to collect frequent repeated measures remotely with minimum disruption to everyday life.

• WHAT QUESTION DID THIS STUDY ADDRESS?

☑ We sought to estimate concordance of mobile and clinic measures, establish patient compliance, assess diurnal variation of FEV₁, and explore whether at‐home repeated FEV1 measures would improve statistical power over traditional clinic measures.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

☑ The mSpirometry FEV1 measurements were strongly correlated with clinic FEV1 from both the same morning (r = 0.993) and same afternoon/evening (r = 0.988). The mean subject compliance with mSpirometry was 85.3%. Our simulation analysis indicated a higher power using dense mSpirometry measurements.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

☑ Deploying mSpirometry in clinical trials is likely to improve statistical power.

Asthma is characterized by airway inflammation, airway hyper‐responsiveness, and variable airflow obstruction. ¹ Despite advances in our understanding of its pathophysiology, biomarker identification, and phenotyping, many patients remain poorly controlled. Asthma displays a strong circadian rhythm, which can cause symptom variability throughout a 24‐hour period. ² , ³ Clinical trials of novel drugs in asthma are faced with the challenge of measuring changes in lung function in this condition, which displays variable airflow obstruction, including diurnal fluctuations.Forced expiratory volume in 1 second (FEV₁) is the gold standard for monitoring lung function in clinical care and research. ⁴ Traditionally, measurements of lung function are performed during clinic visits. However, the frequency of measurements is often limited in clinical trials due to feasibility considerations for patients and cost. Asthma is characterized by airflow obstruction, which displays a diurnal pattern. Diurnal variation is observed in lung function in healthy individuals ⁵ and is greater in patients with asthma. ⁶ The lowest FEV₁ measurements are observed in early morning hours coinciding with increased symptoms and airway inflammation. ⁷ The requirement for clinic visits limits the ability to capture this variability. These limitations impose requirements of a relatively large sample size for drug development clinical trials to control for measurement variability. Furthermore, frequent clinic visits can limit patient participation.It is well known that multiple measures improve the accuracy of a measurement and therefore provide greater statistical power to detect a treatment difference in a measure with fewer patients. ⁸ The ability to monitor FEV₁ frequently may therefore be of benefit in clinical trials that evaluate treatment interventions in asthma. Frequent FEV₁ assessments can also help to account for diurnal variation. FEV₁ monitoring using mobile spirometers (mSpirometers) provides an opportunity to do at‐home monitoring, collect dense data, and minimize the effect of random anomalous tests results that may occur during sparse clinic visits. Although mSpirometers provide convenient means for collecting lung function data at home, a concern about this modality is related to patient compliance and willingness to put the best effort to perform expiratory maneuvers while unsupervised.The recent advances in remote FEV₁ monitoring demonstrated high correlation and small mean differences between at‐home mobile handheld and clinic‐based FEV₁ measurements in the context of randomized clinical trials in asthma ⁹ and chronic obstructive pulmonary disease (COPD). ¹⁰ However, the studies describing a comparison of clinic and mSpirometry data are limited, and study findings may be device‐specific. Moreover, patient compliance with mSpirometry was reported only in patients with COPD, ¹⁰ indicating a need to establish compliance data in different populations, including asthma. Additionally, to our knowledge, no study has investigated if FEV₁ repeated measurements at home can improve statistical power to detect a treatment effect. The aim of our study was to build on previous findings, by verifying agreement between clinic and mobile FEV₁ measurements using a different spirometer device, establishing patient compliance in patients with moderate asthma. Furthermore, we used the data to perform power simulation to estimate the effect sizes that can be detected from either weekly clinic measurements or daily measurements at home in clinical trials.