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Respiratory Current Awareness Newsletter
January 2016
Outreach Your Outreach Librarian can help facilitate evidence-based practice for
all Respiratory staff, as well as assisting with academic study and research. We can help with literature searching, obtaining journal
articles and books, and setting up individual current awareness alerts.
Literature Searching We provide a literature searching service for any library member. For those embarking on their own research it is advisable to book some
time with one of the librarians for a 1 to 1 session where we can guide you through the process of creating a well-focused literature research and introduce you to the health databases access via NHS Evidence.
Critical Appraisal Training We also offer one-to-one or small group training in literature
searching, accessing electronic journals, and critical appraisal/Statistics. These are essential courses that teach how to
interpret clinical papers.
For more information, email: [email protected]
Books Books can be searched for using SWIMS our online catalogue at
www.swims.nhs.uk. Books and journals that are not available on site or electronically may be requested from other locations. Please email
requests to: [email protected]
Contents
1: Tables of Contents from January’s
Respiratory journals
2: New NICE Guidance
3: Latest relevant Systematic Reviews from
the Cochrane Library
4: NHS Behind the Headlines
5: New activity in Uptodate
6: Quick Exercise
7: Current Awareness database articles
Tables of Contents from Respiratory journals
The links below will take you to the full Tables of Contents.
If you require full articles please email: [email protected]
Thorax January 2016, Volume 71, Issue 1
Chest January 2016, Volume 149, Issue 1
European Respiratory Journal January 2016, Volume 47, Issue 1
* * *
The ‘BIG 4’: JAMA January 5, 2016, Volume 315, Issue 1
The New England Journal of Medicine January 7, 2016 Volume 374, Issue 1
The Lancet: Respiratory Medicine January 2016, Volume 4, Issue 1
BMJ: Respiratory Medicine [portal]
New NICE Guidance
PHG In development Tuberculosis (update)
Latest relevant Systematic Reviews from the
Cochrane Library
Interventions for smoking cessation in people diagnosed with lung cancer Intraoperative use of low volume ventilation to decrease postoperative mortality, mechanical ventilation, lengths of stay and lung injury in patients without acute lung injury Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis Home versus hospital intravenous antibiotic therapy for cystic fibrosis Oral steroids for long-term use in cystic fibrosis
Upcoming Lunchtime Drop-in Sessions
February (12pm)
Friday 5th Literature Searching
Monday 8th Understanding articles
Tuesday 16th Statistics
Wednesday 24th Information resources
January (1pm)
Monday 4th Literature searching
Tuesday 12th Critical Appraisal
Wednesday 20th Statistics
Thursday 28th Library Resources
The Library and Information Service provides free specialist information skills training for
all UHBristol staff and students.
To book a place, email: [email protected]
If you’re unable to attend we also provide one-to-one or small group sessions. Contact
[email protected] or [email protected] to arrange a session.
NHS Behind the Headlines
Our news predictions for 2016
Thursday Dec 31 2015
What will be the big health news stories for 2016? We take a look in the Behind the Headlines crystal ball and offer our predictions…
Last line in antibiotic resistance under threat - News update
Tuesday Dec 22 2015
"The last line of antibiotic defence against some serious infections is under threat," The Guardian reports, after researchers found that E.coli bacteria from food products in China has developed resistance to colistin, a polymixin antibiotic…
Active and secondhand smoking both linked to early menopause
Wednesday Dec 16 2015
"Women who are heavy or habitual smokers are more likely to experience the menopause earlier [before the age of 50], a study suggests," BBC News reports. The same study found a weaker link for women exposed to secondhand smoke…
Flavouring found in e-cigarettes linked to 'popcorn lung'
Tuesday Dec 8 2015
"Smokers who use e-cigs 'are risking harm to their lungs'," the Daily Mail reports after US researchers discovered some brands contained diacetyl, a buttery flavouring linked to lung disease in people who worked in microwave popcorn factories…
New activity in Uptodate Mandibular advancement devices lower blood pressure in sleep apnea (December 2015)
Improved blood pressure control is a benefit associated with continuous positive airway pressure
(CPAP) treatment in patients with obstructive sleep apnea (OSA) and hypertension. However, it is
unclear whether therapeutic modalities other than CPAP result in the same benefit. One meta-
analysis of 51 studies of patients with hypertension and OSA reported that compared with patients on
placebo or not receiving therapy, mandibular advancement devices (MADs) were associated with a
significant reduction in systolic and diastolic blood pressure [23]. The level of reduction was similar to
that reported in patients treated with CPAP. While this study does not alter the indications for either
therapy, it suggests that patients with OSA who are treated with MADs may derive similar positive
effects on blood pressure control as those treated with CPAP. (See "Obstructive sleep apnea and
cardiovascular disease", section on 'Impact of treatment'.)
de-mystified… What is OpenAthens? OpenAthens is a way of authenticating that you have permission to access our subscription e-resources. To access our electronic resources you will need a UH Bristol Athens username/password. How can I get an Athens login? Click here to complete the online registration form. You will need to register using a Trust PC and a UH Bristol email address. Once you have successfully completed the form, you will be sent an email to you UH Bristol account with an authentication link. I have an Athens account from another Trust/University. Do I still need a UH Bristol account? You will need a UH Bristol account to access our local subscription resources. You can either update the settings of your existing account by logging in and selecting ‘change organisation’, or you can set up a new UH Bristol account by clicking here (you will need to register using a Trust PC and a UH Bristol email address). My Athens account has expired. What should I do? You can register for a new account here. I have forgotten my Athens Username / Password. How can I reset it? Password: If you are on a Trust PC, follow the link to https://register.athensams.net/nhs/forgotten_password.php. Username and password: You should email [email protected] with your full name, full work address, work telephone number and the email address you used to register for the account. In the email subject line put 'Forgotten username and password'. It may take up to five working days to receive your username and a reset password.
Quick Exercise
Match the diagrams to the corresponding research designs.
1
2
3
A: Randomised Controlled Trial B: Cohort Study C: Case-control Study
Find out more about research designs in one of our Understanding Articles training sessions. For more details, email [email protected].
Current Awareness database articles
If you require full articles please email: [email protected]
Title: Self-help educational booklets for the prevention of smoking relapse following smoking cessation treatment: a randomized controlled trial. Citation: Addiction (Abingdon, England), Dec 2015, vol. 110, no. 12, p. 2006-2014 (December 2015) Author(s): Maskrey, Vivienne, Blyth, Annie, Brown, Tracey J, Barton, Garry R, Notley, Caitlin, Aveyard, Paul, Holland, Richard, Bachmann, Max O, Sutton, Stephen, Leonardi-Bee, Jo, Brandon, Thomas H, Song, Fujian Abstract: Most people who quit smoking for a short term will return to smoking again in 12 months. We tested whether self-help booklets can reduce relapse in short-term quitters after receiving behavioural and pharmacological cessation treatment. A parallel-arm, pragmatic individually randomized controlled trial. Smoking cessation clinics in England. Participants People who stopped smoking for 4 weeks after receiving cessation treatment in stop smoking clinics. Participants in the experimental group (n = 703) were mailed eight booklets, each of which taught readers how to resist urges to smoke. Participants in the control group (n = 704) received a leaflet currently used in practice. The primary outcome was prolonged, carbon monoxide-verified abstinence from months 4 to 12. The secondary outcomes included 7-day self#x02010;reported abstinence at 3 and 12 months. Mixed-effects logistic regression was used to estimate treatment effects and to investigate possible effect modifying variables. There were no statistically significant differences between the groups in prolonged abstinence from months 4 to 12 (36.9% versus 38.6%; odds ratio 0.93, 95% confidence interval 0.75-1.16; P = 0.524). In addition, there were no significant differences between the groups in any secondary outcomes. However, people who reported knowing risky situations for relapse and using strategies to handle urges to smoke were less likely to relapse. In people who stop smoking successfully with behavioural support, a comprehensive self-help educational programme to teach people skills to identify and respond to high-risk situations for return to smoking did not reduce relapse. © 2015 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.
Title: Characteristics and Outcomes of Eligible Nonenrolled Patients in a Mechanical Ventilation Trial of Acute Respiratory Distress Syndrome. Citation: American journal of respiratory and critical care medicine, Dec 2015, vol. 192, no. 11, p. 1306-1313 (December 1, 2015) Author(s): Arabi, Yaseen M, Cook, Deborah J, Zhou, Qi, Smith, Orla, Hand, Lori, Turgeon, Alexis F, Matte, Andrea, Mehta, Sangeeta, Graham, Russell, Brierley, Kristin, Adhikari, Neill K J, Meade, Maureen O, Ferguson, Niall D, Canadian Critical Care Trials Group Abstract: Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion. To describe characteristics and outcomes of eligible nonenrolled (ENE) patients in a multicenter trial
of mechanical ventilation strategies. Within the OSCILLATE trial of high-frequency oscillation (HFO) versus conventional ventilation (CV) in adults with adult respiratory distress syndrome, and with approval from research ethics boards, we collected a minimal dataset on patients who satisfied eligibility criteria but were not enrolled. We categorized ENE patients as ENE-HFO and ENE-CV based on receipt of HFO at any time. We used multivariable logistic regression to assess the association between ENE status and mortality. A total of 548 patients were randomized, and 546 were ENE. The most common reasons for ENE were no consent (42%), physician refusal (24%), missed randomization window (15%), and current HFO use (14%). Compared with randomized patients in respective arms of the trial, ENE-HFO patients were younger and had worse lung injury, whereas ENE-CV patients had lower illness severity. ENE status was independently associated with mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84; P = 0.02), with no significant interaction with ventilation treatment group. Nonenrollment was common, with approximately one ENE patient for every randomized patient. Our study suggests that enrollment in trials of mechanical ventilation may be associated with improved outcomes compared with standard care and highlights the need for prospective tracking and transparent reporting of ENE patients as part of trial management. Full Text: Available from ProQuest in American Journal of Respiratory and Critical Care Medicine
Title: Characteristics of Alpha-1 Antitrypsin-Deficient Individuals in the Long-term Oxygen Treatment Trial and Comparison with Other Subjects with Chronic Obstructive Pulmonary Disease. Citation: Annals of the American Thoracic Society, Dec 2015, vol. 12, no. 12, p. 1796-1804 (December 2015) Author(s): Stoller, James K, Aboussouan, Loutfi S, Kanner, Richard E, Wilson, Laura A, Diaz, Phil, Wise, Robert, LOTT Research Group * Abstract: Alpha-1 antitrypsin deficiency (AATD) predisposes to chronic obstructive pulmonary disease, but is underrecognized. Oxygenation and exercise desaturation in individuals with AATD-associated chronic obstructive pulmonary disease has been sparsely studied. The Long-term Oxygen Treatment Trial (LOTT) permits comparing these features of individuals with AATD with alpha-1 antitrypsin-replete (called "usual chronic obstructive pulmonary disease") LOTT participants. Compare demographic, clinical, baseline oxygenation, and exercise desaturation features in participating AATD subjects with those of other LOTT subjects. LOTT is a multicenter randomized controlled trial comparing use of supplemental oxygen versus not in subjects with chronic obstructive pulmonary disease and moderate hypoxemia (resting oxygen saturation as measured by pulse oximetry, 89-93%) or normal oxygen saturation at rest and significant exercise desaturation. Among the 597 LOTT participants with nonmissing alpha-1 antitrypsin levels, 11 (1.8%) had severe AATD and 44 (7.4%) had mild/moderate AATD. Comparison of the 11 severely AAT-deficient individuals with the 542 LOTT participants with usual chronic obstructive pulmonary disease showed that the AATD subjects were younger and despite less smoking, had lower FEV1/FVC (mean post-bronchodilator FEV1/FVC, 0.38 ± 0.06 vs. 0.46 ± 0.13; P = 0.002). Comparison with 27 age-, sex-, and FEV1-matched alpha-1 antitrypsin-normal LOTT participants showed no baseline difference in resting room air pulse oximetry saturation (AATD, 93.6% ± 2.3% vs. 92.7% ± 2.2%; P = 0.64). Exercise-related desaturation was more severe in the individuals with AATD based on desaturation to 88% or less sooner during a 6-minute-walk test, having a higher percentage of desaturation points (e.g., <90%) during exercise, and having a higher distance-saturation product (defined as the distance walked in 6 min multiplied by the nadir saturation achieved during the 6-minute-walk test). These data suggest that individuals with AATD experience more profound desaturation with exercise than age-, sex-,
race-, and FEV1-matched control subjects with usual chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00692198). Full Text: Available from ProQuest in Annals of the American Thoracic Society
Title: Respiratory Tract Infection Clinical Trials from 2007 to 2012. A Systematic Review of ClinicalTrials.gov. Citation: Annals of the American Thoracic Society, Dec 2015, vol. 12, no. 12, p. 1852-1863 (December 2015) Author(s): Ruopp, Marcus, Chiswell, Karen, Thaden, Joshua T, Merchant, Kunal, Tsalik, Ephraim L Abstract: Respiratory tract infections are highly prevalent and variable, and confer considerable morbidity and mortality. There is a growing need for new treatments for such infections, particularly in the setting of worsening antibacterial resistance. We analyzed data from ClinicalTrials.gov to summarize activity in respiratory infection trials, identify gaps in research activity, and inform efforts to address disparities between antimicrobial resistance and development of new antibacterial drugs. We examined 69,779 interventional trials registered with ClinicalTrials.gov from 2007 to 2012, focusing on study conditions and interventions to identify respiratory infection-related trials. Programmatic identification with manual confirmation yielded 6,253 infectious disease trials, 1,377 respiratory infection trials, and 270 lower respiratory tract infection trials for analysis. The 1,377 respiratory infection trials accounted for 2% of all trials and 22% of infectious diseases trials. Such trials (54.8%) were more likely than either nonrespiratory infectious diseases trials (48.1%) or noninfectious disease trials (42.8%) to receive industry funding. Stratification of respiratory infection trials by registration year demonstrated declining industry funding: 181 (64.9%) in 2007-2008 to 110 (46.0%) in 2011-2012. Respiratory infection trials more frequently evaluated vaccines (52.7 vs. 15.5% of nonrespiratory tract infection trials). Lower respiratory tract infection trials (excluding tuberculosis) focused primarily on bacterial pathogens (78.5%) followed by viral (12.6%), fungal (5.6%), and nontuberculous mycobacterial (3.0%) pathogens. Approximately 40% of 120 lower respiratory tract infection trials that were completed or terminated published results in the literature. On multivariable logistic regression analysis, a treatment focus was associated with decreased odds of publishing results (odds ratio, 0.28; 95% confidence interval, 0.10-0.82; P = 0.02). There were also generally low numbers of studies evaluating novel antimicrobial agents (community-acquired pneumonia, 15.9%; hospital-acquired pneumonia, 16.7%; ventilator-associated pneumonia, 5.3%). From 2007 to 2012, respiratory infection trials did not occur in numbers commensurate with global impact. The number of trials registered per year did not increase throughout the study period, partly due to declining industry support. There was a concerning reduction in prevention-oriented lower respiratory infection trials and an overall low number of such trials involving novel antimicrobials. Full Text: Available from ProQuest in Annals of the American Thoracic Society
Title: Simple Lower Limb Functional Tests in Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review. Citation: Archives of physical medicine and rehabilitation, Dec 2015, vol. 96, no. 12, p. 2221-2230 (December 2015)
Author(s): Bisca, Gianna Waldrich, Morita, Andrea Akemi, Hernandes, Nidia Aparecida, Probst, Vanessa Suziane, Pitta, Fabio Abstract: To evaluate the characteristics and available evidence on the measurement properties of the gait speed (GS) test, timed Up and Go test (TUG), sit-to-stand (STS) test, and step test; to investigate their relation with clinical outcomes in chronic obstructive pulmonary disease (COPD); and to provide recommendations for clinical practice and future research. Studies were systematically identified from a literature search using PubMed, PEDro, CINAHL, and Cochrane Library databases and the reference lists of the included articles. Studies including ≥1 of these 4 lower limb functional tests (GS test, TUG, STS test, and step test) as an outcome in patients with COPD were selected. No limits were applied for language and study design. Two researchers independently performed data extraction and, by using the COnsensus-based standards for the Selection of health status measurement INstruments, assessed the quality of those studies that described measurement properties. Forty-two articles met the selection criteria. GS test, STS test, and step test are valid, reproducible, and responsive tests, especially the 4-meter GS, 5-repetition STS test, and 6-minute step test (6MST). The TUG is reliable; however, studies on other measurement properties of this test are lacking. Outcomes of these tests are correlated with mortality, physical activity in daily life, exercise capacity, dyspnea, and quality of life. Simple and functional lower limb tests provide information about important clinical outcomes in patients with COPD. The 4-meter GS, 5-repetition STS test, and 6MST are tests with well-established psychometric properties, whereas the properties of the TUG need to be studied further. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Title: Nonpharmacological interventions aimed at modifying health and behavioural outcomes for adults with asthma: a critical review. Citation: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, Dec 2015, vol. 45, no. 12, p. 1750-1764 (December 2015) Author(s): Yorke, J, Fleming, S, Shuldham, C, Rao, H, Smith, H E Abstract: Evidence suggests that living with asthma is linked with psychological and behavioural factors including self-management and treatment adherence, and therefore, there is a reasonable hypothesis that nonpharmacological treatments may improve health outcomes in people living with this condition. A systematic review of randomized controlled trials (RCTs) of nonpharmacological interventions for adults with asthma was designed. Databases searched included The Cochrane Airways Group Register of trials, CENTRAL and Psychinfo. The literature search was conducted until May 2014. Twenty-three studies met the inclusion criteria and were organized into four groups: relaxation-based therapies (n = 9); mindfulness (n = 1), biofeedback techniques (n = 3); cognitive behavioural therapies (CBT) (n = 5); and multicomponent interventions (n = 5). A variety of outcome measures were used, even when trials belonged to the same grouping, which limited the ability to conduct meaningful meta-analyses. Deficiencies in the current evidence base, notably trial heterogeneity, means that application to clinical practice is limited and clear guidelines regarding the use of nonpharmacological therapies in asthma is limited. Relaxation and CBT, however, appear to have a consistent positive effect on asthma-related quality of life and some psychological outcomes, and lung function (relaxation only). Future trials should be informed by previous work to harmonize the interventions under study and outcome measures used to determine their effectiveness; only then will meaningful meta-analyses inform clinical practice. © 2015 John Wiley & Sons Ltd.
Title: Long-term effect of respiratory training for chronic obstructive pulmonary disease patients at an outpatient clinic: a randomised controlled trial. Citation: Clinical and translational medicine, Dec 2015, vol. 4, no. 1, p. 31. (December 2015) Author(s): Xi, Fang, Wang, Zheng, Qi, Yong, Brightwell, Richard, Roberts, Peter, Stewart, Angus, Sim, Moira, Wang, Wei Abstract: To assess the effect of respiratory training (RT) on lung function, activity tolerance and acute exacerbation frequency with chronic obstructive pulmonary disease (COPD). A randomised controlled trial. Outpatient clinic and home of the COPD patients, Zhengzhou City, China. Sixty participants with COPD were randomised into two groups: an intervention group (n = 30) which received the RT in self-management and a control group (n = 30) that received an education program during the study. Pulmonary function, activity tolerance and frequency of acute exacerbation of these COPD patients were evaluated before and after the program. The intervention and control programs were delivered at monthly outpatient clinic visits over a period of 12 months. The pulmonary rehabilitation (PR) program was conducted by a physiotherapist (who delivered RT to the participant over a minimum of 1 h per visit) for the intervention group, whereas the control group received routine health education provided by physiotherapists. The intervention group patients were then instructed to perform exercises at home as taught in the RT at least 5 days per week at home. After 12 months of RT, the lung function and the activity tolerance of the COPD patients in the intervention group were significantly improved and the exacerbation frequency was also decreased. Long-term RT can improve lung function and activity tolerance while decreasing the frequency of acute exacerbation for COPD patients. Full Text: Available from ProQuest in Clinical and Translational Medicine Available from BioMed Central in Clinical and Translational Medicine
Title: Tobacco Use, Use Disorders, and Smoking Cessation Interventions in Persons Living With HIV. Citation: Current HIV/AIDS reports, Dec 2015, vol. 12, no. 4, p. 413-420 (December 2015) Author(s): Pacek, Lauren R, Cioe, Patricia A Abstract: Cigarette smoking remains highly prevalent among persons living with human immunodeficiency virus (HIV), estimated to be 40-75 %, and is significantly higher than what is observed among the general population. Health risks of smoking in this population include cardiovascular disease; bacterial pneumonia, chronic obstructive pulmonary disease, and other respiratory conditions; lung cancer and other malignancies; adverse cognitive and neurological outcomes; low birth weight, preterm birth, and small-for-gestational-age infants; and overall mortality. Smokers with HIV now lose more life years to smoking than they do to the HIV itself. A majority of smokers living with HIV report being interested in cessation, and a significant proportion has made recent quit attempts. There is a general paucity of large, randomized controlled trials of smoking cessation interventions among smokers living with HIV, and among the existing research, cessation rates are suboptimal. Greater resources and effort should be allocated to developing and evaluating cessation treatment modalities for smokers living with HIV. Efforts to individualize and tailor treatments to address specific client needs and comorbidities are warranted. HIV care
providers and other health professionals can play a key role in improving health among this population by regularly screening for smoking and promoting cessation.
Title: Diagnostic Accuracy of Rapid Antigen Detection Tests for Respiratory Syncytial Virus Infection: Systematic Review and Meta-analysis. Citation: Journal of clinical microbiology, Dec 2015, vol. 53, no. 12, p. 3738-3749 (December 2015) Author(s): Chartrand, Caroline, Tremblay, Nicolas, Renaud, Christian, Papenburg, Jesse Abstract: Respiratory syncytial virus (RSV) rapid antigen detection tests (RADT) are extensively used in clinical laboratories. We performed a systematic review and meta-analysis to evaluate the accuracy of RADTs for diagnosis of RSV infection and to determine factors associated with accuracy estimates. We searched EMBASE and PubMed for diagnostic-accuracy studies of commercialized RSV RADTs. Studies reporting sensitivity and specificity data compared to a reference standard (reverse transcriptase PCR [RT-PCR], immunofluorescence, or viral culture) were considered. Two reviewers independently extracted data on study characteristics, diagnostic-accuracy estimates, and study quality. Accuracy estimates were pooled using bivariate random-effects regression models. Heterogeneity was investigated with prespecified subgroup analyses. Seventy-one articles met inclusion criteria. Overall, RSV RADT pooled sensitivity and specificity were 80% (95% confidence interval [CI], 76% to 83%) and 97% (95% CI, 96% to 98%), respectively. Positive- and negative-likelihood ratios were 25.5 (95% CI, 18.3 to 35.5) and 0.21 (95% CI, 0.18 to 0.24), respectively. Sensitivity was higher in children (81% [95% CI, 78%, 84%]) than in adults (29% [95% CI, 11% to 48%]). Because of this disparity, further subgroup analyses were restricted to pediatric data (63 studies). Test sensitivity was poorest using RT-PCR as a reference standard and highest using immunofluorescence (74% versus 88%; P < 0.001). Industry-sponsored studies reported significantly higher sensitivity (87% versus 78%; P = 0.01). Our results suggest that the poor sensitivity of RSV RADTs in adults may preclude their use in this population. Furthermore, industry-sponsored studies and those that did not use RT-PCR as a reference standard likely overestimated test sensitivity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Title: Burden of respiratory syncytial virus infections in China: Systematic review and meta-analysis. Citation: Journal of global health, Dec 2015, vol. 5, no. 2, p. 020417. (December 2015) Author(s): Zhang, Yaowen, Yuan, Lichao, Zhang, Yongming, Zhang, Xiuping, Zheng, Minghuan, Kyaw, Moe H Abstract: Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China. A systematic search was performed in the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed to identify available published RSV studies in China. A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1-20.5%). The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7-29.5%) and lowest in those aged ≥16 years (2.8%, 95% CI 1.3-6.1). A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9-24.2%) than in outpatients (14%, 95% CI 9.6-19.9%). RSV type A accounted for 63.1% (95% CI 52.3-72.8%) of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum,
wheezing and fever. RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority.
Title: Anxiety and Depressed Mood Decline Following Smoking Abstinence in Adult Smokers with Attention Deficit Hyperactivity Disorder. Citation: Journal of substance abuse treatment, Dec 2015, vol. 59, p. 104-108 (December 2015) Author(s): Covey, Lirio S, Hu, Mei-Chen, Winhusen, Theresa, Lima, Jennifer, Berlin, Ivan, Nunes, Edward Abstract: A preponderance of relevant research has indicated reduction in anxiety and depressive symptoms following smoking abstinence. This secondary analysis investigated whether the phenomenon extends to smokers with attention deficit hyperactivity disorder (ADHD). The study setting was an 11-Week double-blind placebo-controlled randomized trial of osmotic release oral system methylphenidate (OROS-MPH) as a cessation aid when added to nicotine patch and counseling. Participants were 255 adult smokers with ADHD. The study outcomes are: anxiety (Beck Anxiety Inventory (BAI)) and depressed mood (Beck Depression Inventory II (BDI)) measured one Week and six Weeks after a target quit day (TQD). The main predictor is point-prevalence abstinence measured at Weeks 1 and 6 after TQD. Covariates are treatment (OROS-MPH vs placebo), past major depression, past anxiety disorder, number of cigarettes smoked daily, demographics (age, gender, education, marital status) and baseline scores on the BAI, BDI, and the DSM-IV ADHD Rating Scale. Abstinence was significantly associated with lower anxiety ratings throughout the post-quit period (p<0.001). Depressed mood was lower for abstainers than non-abstainers at Week 1 (p<0.05), but no longer at Week 6 (p=0.83). Treatment with OROS-MPH relative to placebo showed significant reductions at Week 6 after TQD for both anxiety (p<0.05) and depressed mood (p<0.001), but not at Week 1. Differential abstinence effects of gender were observed. Anxiety and depression ratings at baseline predicted increased ratings of corresponding measures during the post-quit period. Stopping smoking yielded reductions in anxiety and depressed mood in smokers with ADHD treated with nicotine patch and counseling. Treatment with OROS-MPH yielded mood reductions in delayed manner. Copyright © 2015 Elsevier Inc. All rights reserved.
Title: Lack of Association Between the IL1B (-511 and +3954), IL1RN VNTR Polymorphisms and Tuberculosis Risk: A Meta-analysis. Citation: Lung, Dec 2015, vol. 193, no. 6, p. 985-992 (December 2015) Author(s): Huang, Qiu-Pin, Liao, Ning, Zhao, Hua, Chen, Min-Li, Xie, Zheng-Fu Abstract: Several recent studies have provided evidence that polymorphisms in the interleukin-1 (IL1) gene are implicated in tuberculosis (TB). However, results of different studies are inconsistent. The aim of this study was to perform a meta-analysis investigating the association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk. A systematic review of the English literature was conducted by searching Pubmed, Scopus, and ISI Web of Knowledge databases for relevant studies. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated using fixed effects models. Between-study heterogeneity and publication bias were also evaluated. Nine case-control studies including 3327 participants were reviewed and analyzed. Our results did not
indicate any association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk in the overall populations. The pooled OR of the IL1B -511 polymorphism was 1.09 (95 % CI 0.87-1.36) for the dominant model, 1.11 (0.89-1.38) for the recessive model, 1.15 (0.87-1.50) for the homozygote model, and 1.07 (0.94-1.23) for the allelic comparison model. ORs for the IL1B +3954 and IL1RN VNTR polymorphisms were similar. In subgroup analysis stratified by ethnicity, the results revealed no association between these polymorphisms and TB risk in black people, Asians, and Caucasians, respectively. We did not identify significant between-study heterogeneity across all studies, and there was no evidence of publication bias. Our results indicate there is a lack of association between the IL1B (-511 and +3954), IL1RN VNTR polymorphisms and TB risk.
Title: Can Vitamin D Supplementation in Addition to Asthma Controllers Improve Clinical Outcomes in Patients With Asthma?: A Meta-Analysis. Citation: Medicine, Dec 2015, vol. 94, no. 50, p. e2185. (December 2015) Author(s): Luo, Jian, Liu, Dan, Liu, Chun-Tao Abstract: Effects of vitamin D on acute exacerbation, lung function, and fraction of exhaled nitric oxide (FeNO) in patients with asthma are controversial. We aim to further evaluate the roles of vitamin D supplementation in addition to asthma controllers in asthmatics.From 1946 to July 2015, we searched the PubMed, Embase, Medline, Cochrane Central Register of Controlled Trials, and ISI Web of Science using "Vitamin D," "Vit D," or "VitD" and "asthma," and manually reviewed the references listed in the identified articles. Randomized controlled trials which reported rate of asthma exacerbations and adverse events, forced expiratory volume in 1 s (FEV1, % of predicted value), FeNO, asthma control test (ACT), and serum 25-hydroxyvitamin D levels were eligible. We conducted the heterogeneities test and sensitivity analysis of the enrolled studies, and random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference for dichotomous and continuous data, respectively. Cochrane systematic review software Review Manager (RevMan) was used to test the hypothesis by Mann-Whitney U test, which were displayed in Forest plots.Seven trials with a total of 903 patients with asthma were pooled in our final studies. Except for asthma exacerbations (I2 = 81%, χ2 = 10.28, P = 0.006), we did not find statistical heterogeneity in outcome measures. The pooled RR of asthma exacerbation was 0.66 (95% confidence interval: 0.32-1.37), but without significant difference (z = 1.12, P = 0.26), neither was in FEV1 (z = 0.30, P = 0.77), FeNO (z = 0.28, P = 0.78), or ACT (z = 0.92, P = 0.36), although serum 25-hydroxyvitamin D was significantly increased (z = 6.16, P < 0.001).Vitamin D supplementation in addition to asthma controllers cannot decrease asthma exacerbation and FeNO, nor improve lung function and asthma symptoms, although it can be safely applied to increase serum 25-hydroxyvitamin D levels.
Title: Antitussive effect of a fixed combination of Justicia adhatoda, Echinacea purpurea and Eleutherococcus senticosus extracts in patients with acute upper respiratory tract infection: A comparative, randomized, double-blind, placebo-controlled study. Citation: Phytomedicine : international journal of phytotherapy and phytopharmacology, Dec 2015, vol. 22, no. 13, p. 1195-1200 (December 1, 2015) Author(s): Barth, Anders, Hovhannisyan, Areg, Jamalyan, Kristina, Narimanyan, Mikael
Abstract: Kan Jang® oral solution (KJ) is a fixed combination of aqueous ethanolic extracts of Justicia adhatoda L. leaf, Echinacea purpurea (L.) Moench root, and Eleutherococcus senticosus (Rupr. & Maxim.) Harms root. It is approved in Scandinavia as an herbal medicinal product for respiratory tract infection treatment. The present clinical trial aimed to compare the antitussive effect of KJ with placebo (PL) and bromhexine (BH) among patients of 18-65 years old with non-complicated upper respiratory infections (URI; i.e., common cold). We performed a parallel-group, randomized, double-blinded, placebo-controlled trial in in 177 patients with acute URI over a 5 day period. We investigated the antitussive effects of a KJ (30 ml/day; 762 mg genuine extracts with standardized contents of 0.2 mg/ml vasicine, 0.8 mg/ml chicoric acid, and 0.03 mg/ml eleutherosides B and E), bromhexine hydrochloride (24 mg/30 ml/day) and PL on cough and blood markers. The primary outcome was cough relief, which was assessed as the change of cough frequency from baseline (cough index). Secondary outcomes were safety with regards to reported adverse events (AEs) and hematological data. Both KJ and BH relieved cough more effectively than placebo. On the third and fourth days of treatment, we observed faster improvement in the group receiving KJ compared to in the groups receiving BH (100%) or PL (100%), indicating a slightly shorter recovery time in the KJ group. KJ showed a good tolerability and safety profile. KJ exerted significant antitussive effects in URI. The present data further support the therapeutic use of KJ in upper respiratory tract infections. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.
Title: Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study. Citation: PLoS medicine, Dec 2015, vol. 12, no. 12, p. e1001932. (December 2015) Author(s): Yuen, Courtney M, Kurbatova, Ekaterina V, Tupasi, Thelma, Caoili, Janice Campos, Van Der Walt, Martie, Kvasnovsky, Charlotte, Yagui, Martin, Bayona, Jaime, Contreras, Carmen, Leimane, Vaira, Ershova, Julia, Via, Laura E, Kim, HeeJin, Akksilp, Somsak, Kazennyy, Boris Y, Volchenkov, Grigory V, Jou, Ruwen, Kliiman, Kai, Demikhova, Olga V, Vasilyeva, Irina A, Dalton, Tracy, Cegielski, J Peter Abstract: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen. We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent
of disease on chest radiograph. In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen). The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse. MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens. Full Text: Available from ProQuest in PLoS Medicine Available from National Library of Medicine in PLoS Medicine
Title: Evidence for Autonomic Function and Its Influencing Factors in Subjects With COPD: A Systematic Review. Citation: Respiratory care, Dec 2015, vol. 60, no. 12, p. 1841-1851 (December 2015) Author(s): Mohammed, Jibril, Meeus, Mira, Derom, Eric, Da Silva, Hellen, Calders, Patrick Abstract: Cardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and nonsystematic reviews have increasingly reported autonomic function impairment in these subjects. For a better understanding, this systematic review was performed to evaluate not only the evidence for autonomic function impairment, but also factors influencing it. The results of the studies reviewed showed a strong level of evidence to support the impairment of heart rate variability in the time domain. A similar evidence level was also found to support impairment in baroreceptor sensitivity and muscle sympathetic nerve activity. Furthermore, this review identified physical activity level, muscle function, and circadian rhythm as the major influencing factors (strong evidence) of autonomic function in subjects with COPD. However, no definite conclusion could be reached for factors such as dyspnea, anxiety, body composition, pulmonary function, age, breathing frequency, ventilatory effort, quality of life, and disease severity due to limited, conflicting, or lack of existing evidence. The results of this review highlight relevant clinical messages for clinicians and other health-care providers regarding the role autonomic function can play as an important physiological marker for prognostication and stratification. Hence, autonomic function outcomes should be identified and considered during management of patients with COPD. Moreover, this review can
serve as basis for future research aimed at assessing the interventions for autonomic function abnormalities in these patients. Copyright © 2015 by Daedalus Enterprises.
Title: Postoperative Noninvasive Ventilation Following Cardiothoracic Surgery: A Clinical Primer and Review of the Literature. Citation: Seminars in cardiothoracic and vascular anesthesia, Dec 2015, vol. 19, no. 4, p. 302-308 (December 2015) Author(s): Gilliland, Samuel, Brainard, Jason Abstract: Postoperative pulmonary complications following cardiac and thoracic surgery are common and associated with significant morbidity and mortality. Noninvasive ventilation has emerged as a successful and well-validated strategy to treat various acute medical conditions. More recently, noninvasive ventilation has been studied in selective surgical patient populations with the goal of preventing postoperative complications and treating acute respiratory failure. In this clinical review, we will briefly examine the incidence of pulmonary complications following cardiothoracic surgery and the physiology and mechanics of acute respiratory failure and noninvasive ventilation. We then present a systematic review of the indications, patient selection, and current literature investigating the specific use of noninvasive ventilation in this population. © The Author(s) 2015.
Title: Risk of active tuberculosis in chronic kidney disease: a systematic review and meta-analysis. Citation: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, Dec 2015, vol. 19, no. 12, p. 1493-1499 (December 2015) Author(s): Al-Efraij, K, Mota, L, Lunny, C, Schachter, M, Cook, V, Johnston, J Abstract: Although the global prevalence of chronic kidney disease (CKD) is increasing, the relationship between CKD and active TB is not well described. To conduct a systematic review to evaluate active TB risk in CKD populations. We searched Ovid Medline, EMBASE and Cochrane databases and relevant journals to identify multicentre or regional studies reporting quantitative effect estimates of an association between CKD and active TB. Risk ratios and rate ratios were used as common measures of association. Pooled estimates were generated using a random-effects model. Of 3406 papers screened, 12 eligible studies were identified with 71 374 end-stage renal disease (ESRD) patients and 560 TB cases. Meta-analysis of adjusted rate ratio data in dialysis populations showed an increased rate of 3.62 (95%CI 1.79-7.33, P < 0.001) compared to the general population, while unadjusted risk ratio data in transplant populations showed an increased risk of 11.35 (95%CI 2.97-43.41) compared to the general population. We found consistent evidence of an increased risk of active TB in ESRD compared to the general population. This relationship persisted despite variability in study population, design and renal replacement therapy (RRT) modality. Further research into the role of comorbidities, RRT modality and CKD stage is required to better understand the association between CKD and active TB.
Title: IL-17 polymorphisms and asthma risk: a meta-analysis of 11 single nucleotide polymorphisms.
Citation: The Journal of asthma : official journal of the Association for the Care of Asthma, Dec 2015, vol. 52, no. 10, p. 981-988 (December 2015) Author(s): Jin, Yan, Deng, Zaichun, Cao, Chao, Li, Longxiang Abstract: There has been significant interest in the association between asthma and the polymorphisms of IL-17A and IL-17F for a period of time. This work aims to present a clearer relationship between asthma and the polymorphisms of IL-17A and IL-17F. Searches were performed in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between polymorphisms of IL-17A and IL-17F and asthma. Nine studies comprising 3650 asthmatics and 3370 controls were included in this meta-analysis for all single nucleotide polymorphisms (SNPs) (2-6 per SNP). Our study examined the polymorphisms of IL-17F rs1889570 (C/T) (CC versus TT: OR = 0.55, 95%CI = 0.41-0.75; CT versus TT: OR = 0.54, 95%CI = 0.40-0.72; CC/CT versus TT: OR = 0.55, 95%CI = 0.42-0.72; CC versus CT/TT, OR = 1.83, 95%CI = 1.39-2.41), IL-17A rs4711998(A/G) (AA/AG versus GG: OR = 0.67, 95%CI = 0.46-0.98), and IL-17A rs3819024(A/G) (AA versus GG: OR = 1.77, 95%CI = 1.39-2.25) and found they were significantly related to the risk of asthma. Our systematic review showed that IL-17F rs1889570(C/T), IL-17A rs4711998(A/G) and IL-17A rs3819024(A/G) may be potential risk factors for asthma susceptibility.
Title: Use of asthma control indicators in measuring inhaled corticosteroid effectiveness in asthmatic smokers: a systematic review. Citation: The Journal of asthma : official journal of the Association for the Care of Asthma, Dec 2015, vol. 52, no. 10, p. 996-1005 (December 2015) Author(s): Hayes, Claire E, Nuss, Henry J, Tseng, Tung-Sung, Moody-Thomas, Sarah Abstract: The objective of this review is to explore how current research measures the effectiveness of inhaled corticosteroids (ICS) in smokers with asthma. PubMed, CINAHL and PsycINFO databases were searched for combinations of terms relating to asthma, tobacco use and ICS effectiveness. The search was limited to articles published between 2004 and 2015, in English language. Studies met inclusion criteria if reporting the use of guideline-based asthma control indicators to measure the therapeutic effects of ICS or ICS combination therapies. This review did not exclude articles based on study design. Data were extracted and summarized to describe how indicators were measured across studies in order to characterize and describe the effects of ICS in smokers. Thirteen studies were included in this review. Six of these 13 studies used only one indicator to measure asthma control in smokers and ICS was found to improve asthma in only one of six of these studies. Of studies evaluating combination therapy, three of four studies reported a therapeutic benefit to smokers. In these studies of combination therapy multiple indicators of control were measured to assess drug effects. To assess the therapeutic benefit of ICS drugs in smokers, multiple indicators should be measured to determine if current therapy is improving asthma control. Asthma therapy should then be adjusted based on the patient's current asthma status. The development of clinical treatment guidelines for asthmatic smokers may help clinicians make best-practice, evidence-based recommendations in order to optimize care for these patients.
Title: Serum Procalcitonin Measurement and Viral Testing to Guide Antibiotic Use for Respiratory Infections in Hospitalized Adults: A Randomized Controlled Trial.
Citation: The Journal of infectious diseases, Dec 2015, vol. 212, no. 11, p. 1692-1700 (December 1, 2015) Author(s): Branche, Angela R, Walsh, Edward E, Vargas, Roberto, Hulbert, Barbara, Formica, Maria A, Baran, Andrea, Peterson, Derick R, Falsey, Ann R Abstract: Viral lower respiratory tract illness (LRTI) frequently causes adult hospitalization and is linked to antibiotic overuse. European studies suggest that the serum procalcitonin (PCT) level may be used to guide antibiotic therapy. We conducted a trial assessing the feasibility of using PCT algorithms with viral testing to guide antibiotic use in a US hospital. Three hundred patients hospitalized with nonpneumonic LRTI during October 2013-April 2014 were randomly assigned at a ratio of 1:1 to receive standard care or PCT-guided care and viral PCR testing. The primary outcome was antibiotic exposure, and safety was assessed at 1 and 3 months. Among the 151 patients in the intervention group, viruses were identified in 42% (63), and 83% (126) had PCT values of <0.25 μg/mL. There were no significant differences in antibiotic use or adverse events between intervention patients and those in the nonintervention group. Subgroup analyses revealed fewer subjects with positive results of viral testing and low PCT values who were discharged receiving antibiotics (20% vs 45%; P = .002) and shorter antibiotic durations among algorithm-adherent intervention patients versus nonintervention patients (2.0 vs 4.0 days; P = .004). Compared with historical controls (from 2008-2011), antibiotic duration in nonintervention patients decreased by 2 days (6.0 vs 4.0 days; P < .001), suggesting a study effect. Although antibiotic use was similar in the 2 arms, subgroup analyses of intervention patients suggest that physicians responded to viral and biomarker data. These data can inform the design of future US studies. NCT01907659. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Title: Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial. Citation: The Lancet. Respiratory medicine, Dec 2015, vol. 3, no. 12, p. 953-962 (December 2015) Author(s): Spertini, François, Audran, Régine, Chakour, Reza, Karoui, Olfa, Steiner-Monard, Viviane, Thierry, Anne-Christine, Mayor, Carole E, Rettby, Nils, Jaton, Katia, Vallotton, Laure, Lazor-Blanchet, Catherine, Doce, Juana, Puentes, Eugenia, Marinova, Dessislava, Aguilo, Nacho, Martin, Carlos Abstract: Tuberculosis remains one of the world's deadliest transmissible diseases despite widespread use of the BCG vaccine. MTBVAC is a new live tuberculosis vaccine based on genetically attenuated Mycobacterium tuberculosis that expresses most antigens present in human isolates of M tuberculosis. We aimed to compare the safety of MTBVAC with BCG in healthy adult volunteers. We did this single-centre, randomised, double-blind, controlled phase 1 study at the Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland). Volunteers were eligible for inclusion if they were aged 18-45 years, clinically healthy, HIV-negative and tuberculosis-negative, and had no history of active tuberculosis, chemoprophylaxis for tuberculosis, or BCG vaccination. Volunteers fulfilling the inclusion criteria were randomly assigned to three cohorts in a dose-escalation manner. Randomisation was done centrally by the CHUV Pharmacy and treatments were masked from the study team and volunteers. As participants were recruited within each cohort, they were randomly assigned 3:1 to receive MTBVAC or BCG. Of the participants allocated MTBVAC, those in the first cohort received 5 × 10(3) colony forming units (CFU) MTBVAC, those in the second cohort received 5 × 10(4) CFU MTBVAC, and those in the third cohort received 5 × 10(5) CFU MTBVAC. In all cohorts, participants assigned to receive BCG were given 5 × 10(5) CFU BCG. Each
participant received a single intradermal injection of their assigned vaccine in 0·1 mL sterile water in their non-dominant arm. The primary outcome was safety in all vaccinated participants. Secondary outcomes included whole blood cell-mediated immune response to live MTBVAC and BCG, and interferon γ release assays (IGRA) of peripheral blood mononuclear cells. This trial is registered with ClinicalTrials.gov, number NCT02013245. Between Jan 23, 2013, and Nov 6, 2013, we enrolled 36 volunteers into three cohorts, each of which consisted of nine participants who received MTBVAC and three who received BCG. 34 volunteers completed the trial. The safety of vaccination with MTBVAC at all doses was similar to that of BCG, and vaccination did not induce any serious adverse events. All individuals were IGRA negative at the end of follow-up (day 210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was at least as immunogenic as BCG. At the same dose as BCG (5×10(5) CFU), although no statistical significance could be achieved, there were more responders in the MTBVAC group than in the BCG group, with a greater frequency of polyfunctional CD4+ central memory T cells. To our knowledge, MTBVAC is the first live-attenuated M tuberculosis vaccine to reach clinical assessment, showing similar safety to BCG. MTBVAC seemed to be at least as immunogenic as BCG, but the study was not powered to investigate this outcome. Further plans to use more immunogenicity endpoints in a larger number of volunteers (adults and adolescents) are underway, with the aim to thoroughly characterise and potentially distinguish immunogenicity between MTBVAC and BCG in tuberculosis-endemic countries. Combined with an excellent safety profile, these data support advanced clinical development in high-burden tuberculosis endemic countries. Biofabri and Bill & Melinda Gates Foundation through the TuBerculosis Vaccine Initiative (TBVI). Copyright © 2015 Elsevier Ltd. All rights reserved.
Title: Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review. Citation: Therapeutic advances in musculoskeletal disease, Dec 2015, vol. 7, no. 6, p. 247-267, 1759-720X (December 2015) Author(s): Iqbal, Kundan, Kelly, Clive Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5-1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease.
Title: Diseases masking and delaying the diagnosis of urogenital tuberculosis. Citation: Therapeutic advances in urology, Dec 2015, vol. 7, no. 6, p. 331-338, 1756-2872 (December 2015) Author(s): Kulchavenya, Ekaterina, Kholtobin, Denis Abstract: As urogenital tuberculosis (UGTB) has no specific clinical features, it is often overlooked. To identify some of the reasons for misdiagnosing UGTB we performed a systematic review. We searched in Medline/PubMed papers with keywords 'urogenital tuberculosis, rare' and 'urogenital tuberculosis, unusual'. 'Urogenital tuberculosis, rare' presented 230 articles and 'urogenital tuberculosis, unusual' presented 81 articles only, a total of 311 papers. A total of 34 papers were duplicated and so were excluded from the review. In addition, we excluded from the analysis 33 papers on epidemiological studies and literature reviews, papers describing non-TB cases and cases of TB another than urogenital organs (48 articles), cases of congenital TB (three articles), UGTB as a case of concomitant disease (16 articles), and UGTB as a complication of BCG-therapy (eight articles). We also excluded 22 articles dedicated to complications of the therapy, which made a total of 164 articles. Among the remaining 147 articles we selected 43 which described really unusual, difficult to diagnose cases. We also included in our review a WHO report from 2014, and one scientific monograph on TB urology. The most frequent reasons for delayed diagnosis were absence typical clinical features of UGTB, and the tendency of UGTB to hide behind the mask of another disease. We can conclude that actually UGTB is not rare disease, but it is often an overlooked disease. The main reasons for delayed diagnosis are vague, atypical clinical features and a low index of suspicion.
Title: Interferon gamma release assays for monitoring the response to treatment for tuberculosis: A systematic review. Citation: Tuberculosis (Edinburgh, Scotland), Dec 2015, vol. 95, no. 6, p. 639-650 (December 2015) Author(s): Clifford, Vanessa, He, Yu, Zufferey, Christel, Connell, Tom, Curtis, Nigel Abstract: The ability to monitor the response to therapy for tuberculosis (TB) and confirm adequate treatment would be a major advance. The utility of interferon gamma assays (IGRA) for this purpose remains uncertain. A systematic search of all studies investigating commercial IGRA to monitor anti-tuberculous treatment was done. Studies were included if they included an IGRA before the start of, and at least once during, treatment for active or latent TB. We identified 30 studies, of which 24 used QuantiFERON-TB (QFT), three used T-SPOT.TB and three used both QFT and T-SPOT.TB. Most studies were done in low TB incidence countries. No uniform pattern was seen in IGRA conversion and reversion rates at the end of treatment for active or latent TB. In most studies, the majority of IGRA results remained positive at the end of treatment. In many studies, the quantitative levels of IFN-γ decreased during treatment, particularly in active TB. There was significant heterogeneity in the included studies. While quantitative IGRA responses generally fall during treatment for TB, the large degree of variation in results between participants in each study means that IGRAs are unlikely to be useful for monitoring anti-tuberculous treatment in clinical practice for any individual patient. Copyright © 2015 Elsevier Ltd. All rights reserved.
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