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1دورية أكاديمية
المصدر: Kerman, Hannah M., Bhushan R. Deshpande, Faith Selzer, Elena Losina, and Jeffrey N. Katz. 2018. “Willingness of older adults to participate in a randomized trial of conservative therapies for knee pain: A prospective preference assessment.” Contemporary Clinical Trials Communications 9 (1): 93-97. doi:10.1016/j.conctc.2017.12.006. http://dx.doi.org/10.1016/j.conctc.2017.12.006Test.
الوصف: Background: In preparation for a trial of physical therapy (PT) for patients with degenerative meniscal tear and knee osteoarthritis, we conducted a prospective preference assessment -- a methodology for estimating the proportion of eligible subjects who would participate in a hypothetical randomized trial. Methods: We identified patients seeking care from the practices of five orthopedic surgeons. Patients completed a survey asking about their willingness to participate in a hypothetical trial, their treatment preferences, their knee pain, and demographic variables. Results: We approached 201 eligible patients, of whom 67% (95% confidence interval [CI] 60%, 73%) completed questionnaires. Of these, 24% (95% CI 17%, 31%) were definitely and 39% (95% CI 31%, 47%) were probably willing to participate in the trial. Thirty-three percent (95% CI 23%, 43%) of subjects with no treatment preference were definitely willing to participate as compared to 9% (95% CI 1%, 17%) with treatment preference (p = .001). Patients with higher educational attainment also stated a greater willingness to participate than those with less education (p = .06). In multivariable logistic regression analysis, those with no treatment preferences had greater adjusted odds of stating they would definitely participate than those with a defined treatment preference (OR 5.2, 95% CI 1.7, 16.2), while subjects with an associate's degree or greater were more likely to state they would definitely participate than those with less education (OR 3.9, 95% CI 1.1, 14.1). Conclusion: In this prospective preference assessment, 63% (95% CI 55%, 71%) of subjects with degenerative meniscal tear expressed willingness to participate in a trial of PT modalities. Individuals with no treatment preferences were more likely to state they would participate than were those with higher education. This methodology can help investigators estimate recruitment rates, anticipate generalizability of the trial sample and create strategies to facilitate enrollment.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898571/pdfTest/; Contemporary Clinical Trials Communications
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2دورية أكاديمية
المؤلفون: Winter, Amelia R., Collins, Jamie E., Katz, Jeffrey N.
المصدر: Winter, Amelia R., Jamie E. Collins, and Jeffrey N. Katz. 2017. “The likelihood of total knee arthroplasty following arthroscopic surgery for osteoarthritis: a systematic review.” BMC Musculoskeletal Disorders 18 (1): 408. doi:10.1186/s12891-017-1765-0. http://dx.doi.org/10.1186/s12891-017-1765-0Test.
مصطلحات موضوعية: Osteoarthritis, Total knee arthroplasty, Arthroscopic partial meniscectomy, Arthroscopy
الوصف: Background: Arthroscopic surgery is a common treatment for knee osteoarthritis (OA), particularly for symptomatic meniscal tear. Many patients with knee OA who have arthroscopies go on to have total knee arthroplasty (TKA). Several individual studies have investigated the interval between knee arthroscopy and TKA. Our objective was to summarize published literature on the risk of TKA following knee arthroscopy, the duration between arthroscopy and TKA, and risk factors for TKA following knee arthroscopy. Methods: We searched PubMed, Embase, and Web of Science for English language manuscripts reporting TKA following arthroscopy for knee OA. We identified 511 manuscripts, of which 20 met the inclusion criteria and were used for analysis. We compared the cumulative incidence of TKA following arthroscopy in each study arm, stratifying by type of data source (registry vs. clinical), and whether the study was limited to older patients (≥ 50) or those with more severe radiographic OA. We estimated cumulative incidence of TKA following arthroscopy by dividing the number of TKAs among persons who underwent arthroscopy by the number of persons who underwent arthroscopy. Annual incidence was calculated by dividing cumulative incidence by the mean years of follow-up. Results: Overall, the annual incidence of TKA after arthroscopic surgery for OA was 2.62% (95% CI 1.73–3.51%). We calculated the annual incidence of TKA following arthroscopy in four separate groups defined by data source (registry vs. clinical cohort) and whether the sample was selected for disease progression (either age or OA severity). In unselected registry studies the annual TKA incidence was 1.99% (95% CI 1.03–2.96%), compared to 3.89% (95% CI 0.69–7.09%) in registry studies of older patients. In unselected clinical cohorts the annual incidence was 2.02% (95% CI 0.67–3.36%), while in clinical cohorts with more severe OA the annual incidence was 4.13% (95% CI 1.81–6.44%). The mean and median duration between arthroscopy and TKA (years) were 3.4 and 2.0 years. Conclusions: Clinicians and patients considering knee arthroscopy should discuss the likelihood of subsequent TKA as they weigh risks and benefits of surgery. Patients who are older or have more severe OA are at particularly high risk of TKA. Electronic supplementary material The online version of this article (10.1186/s12891-017-1765-0) contains supplementary material, which is available to authorized users.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628417/pdfTest/; BMC Musculoskeletal Disorders
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3دورية أكاديمية
المؤلفون: Lim, Christopher T., Roberts, Heather J., Collins, Jamie E., Losina, Elena, Katz, Jeffrey N.
المصدر: Lim, Christopher T., Heather J. Roberts, Jamie E. Collins, Elena Losina, and Jeffrey N. Katz. 2017. “Factors influencing the enrollment in randomized controlled trials in orthopedics.” Contemporary Clinical Trials Communications 8 (1): 203-208. doi:10.1016/j.conctc.2017.10.005. http://dx.doi.org/10.1016/j.conctc.2017.10.005Test.
مصطلحات موضوعية: Orthopedics, Randomized controlled trials, Recruitment
الوصف: Background: Low enrollment rates are a threat to the external validity of clinical trials. The purpose of this study was to identify factors associated with lower enrollment rates in randomized controlled trials (RCTs) involving orthopedic procedures. Methods: We performed a search in PubMed/MEDLINE for RCTs that involved any orthopedic surgical procedure, compared different intraoperative interventions, were published in English in a peer-reviewed journal between 2003 and 2014, and reported the numbers of both enrolled and eligible subjects. The primary outcome was the enrollment rate, defined as the number of enrolled subjects divided by the number of eligible subjects. We used a meta-regression to identify factors associated with lower enrollment rates. Results: The combined estimate of enrollment rate across all 393 studies meeting inclusion criteria was 90% (95% CI: 89–92%). Trials in North America had significantly lower enrollment rates compared to trials in the rest of the world (80% vs. 92%, p < 0.0001). Trials comparing operative and non-operative treatments had significantly lower enrollment rates than trials comparing two different operative interventions (80% vs. 91%, p < 0.0001). Among trials comparing operative and non-operative interventions, there was a marked difference in enrollment rate by region: 49% in North America and 86% elsewhere (p < 0.0001). Conclusions: RCTs investigating orthopedic procedures have variable enrollment rates depending on their location and the difference between the interventions being studied. North American trials that compare operative and non-operative interventions have the lowest enrollment rates. Investigators planning RCTs would be well advised to consider these data in planning recruitment efforts.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898493/pdfTest/; Contemporary Clinical Trials Communications
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4دورية أكاديمية
المؤلفون: Losina, Elena, Smith, Savannah R., Usiskin, Ilana M., Klara, Kristina M., Michl, Griffin L., Deshpande, Bhushan R., Yang, Heidi Y., Smith, Karen C., Collins, Jamie E., Katz, Jeffrey N.
المصدر: Losina, Elena, Savannah R. Smith, Ilana M. Usiskin, Kristina M. Klara, Griffin L. Michl, Bhushan R. Deshpande, Heidi Y. Yang, Karen C. Smith, Jamie E. Collins, and Jeffrey N. Katz. 2017. “Implementation of a workplace intervention using financial rewards to promote adherence to physical activity guidelines: a feasibility study.” BMC Public Health 17 (1): 921. doi:10.1186/s12889-017-4931-2. http://dx.doi.org/10.1186/s12889-017-4931-2Test.
مصطلحات موضوعية: Physical activity, Workplace, Exercise, Financial incentives
الوصف: Background: We designed and implemented the Brigham and Women’s Wellness Initiative (B-Well), a single-arm study to examine the feasibility of a workplace program that used individual and team-based financial incentives to increase physical activity among sedentary hospital employees. Methods: We enrolled sedentary, non-clinician employees of a tertiary medical center who self-reported low physical activity. Eligible participants formed or joined teams of three members and wore Fitbit Flex activity monitors for two pre-intervention weeks followed by 24 weeks during which they could earn monetary rewards. Participants were rewarded for increasing their moderate-to-vigorous physical activity (MVPA) by 10% from the previous week or for meeting the Centers for Disease Control and Prevention (CDC) physical activity guidelines (150 min of MVPA per week). Our primary outcome was the proportion of participants meeting weekly MVPA goals and CDC physical activity guidelines. Secondary outcomes included Fitbit-wear adherence and factors associated with meeting CDC guidelines more consistently. Results: B-Well included 292 hospital employees. Participants had a mean age of 38 years (SD 11), 83% were female, 38% were obese, and 62% were non-Hispanic White. Sixty-three percent of participants wore the Fitbit ≥4 days per week for ≥20 weeks. Two-thirds were satisfied with the B-Well program, with 79% indicating that they would participate again. Eighty-six percent met either their personal weekly goal or CDC physical activity guidelines for at least 6 out of 24 weeks, and 52% met their goals or CDC physical activity guidelines for at least 12 weeks. African Americans, non-obese subjects, and those with lower impulsivity scores reached CDC guidelines more consistently. Conclusions: Our data suggest that a financial incentives-based workplace wellness program can increase MVPA among sedentary employees. These results should be reproduced in a randomized controlled trial. Trial registration Clinicaltrials.gov, NCT02850094. Registered July 27, 2016 [retrospectively registered].
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709939/pdfTest/; BMC Public Health
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5دورية أكاديمية
المؤلفون: Barbhaiya, Medha, Dong, Yan, Sparks, Jeffrey A., Losina, Elena, Costenbader, Karen H., Katz, Jeffrey N.
المصدر: Barbhaiya, Medha, Yan Dong, Jeffrey A. Sparks, Elena Losina, Karen H. Costenbader, and Jeffrey N. Katz. 2017. “Administrative Algorithms to identify Avascular necrosis of bone among patients undergoing upper or lower extremity magnetic resonance imaging: a validation study.” BMC Musculoskeletal Disorders 18 (1): 268. doi:10.1186/s12891-017-1626-x. http://dx.doi.org/10.1186/s12891-017-1626-xTest.
مصطلحات موضوعية: Avascular necrosis, Avn, Osteonecrosis, Epidemiology, Magnetic, Resonance Imaging, MRI, administrative data, validation
الوصف: Background: Studies of the epidemiology and outcomes of avascular necrosis (AVN) require accurate case-finding methods. The aim of this study was to evaluate performance characteristics of a claims-based algorithm designed to identify AVN cases in administrative data. Methods: Using a centralized patient registry from a US academic medical center, we identified all adults aged ≥18 years who underwent magnetic resonance imaging (MRI) of an upper/lower extremity joint during the 1.5 year study period. A radiologist report confirming AVN on MRI served as the gold standard. We examined the sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratio (LR+) of four algorithms (A-D) using International Classification of Diseases, 9th edition (ICD-9) codes for AVN. The algorithms ranged from least stringent (Algorithm A, requiring ≥1 ICD-9 code for AVN [733.4X]) to most stringent (Algorithm D, requiring ≥3 ICD-9 codes, each at least 30 days apart). Results: Among 8200 patients who underwent MRI, 83 (1.0% [95% CI 0.78–1.22]) had AVN by gold standard. Algorithm A yielded the highest sensitivity (81.9%, 95% CI 72.0–89.5), with PPV of 66.0% (95% CI 56.0–75.1). The PPV of algorithm D increased to 82.2% (95% CI 67.9–92.0), although sensitivity decreased to 44.6% (95% CI 33.7–55.9). All four algorithms had specificities >99%. Conclusion: An algorithm that uses a single billing code to screen for AVN among those who had MRI has the highest sensitivity and is best suited for studies in which further medical record review confirming AVN is feasible. Algorithms using multiple billing codes are recommended for use in administrative databases when further AVN validation is not feasible.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477300/pdfTest/; BMC Musculoskeletal Disorders
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6دورية أكاديمية
المصدر: Losina, Elena, Heidi Y. Yang, Bhushan R. Deshpande, Jeffrey N. Katz, and Jamie E. Collins. 2017. “Physical activity and unplanned illness-related work absenteeism: Data from an employee wellness program.” PLoS ONE 12 (5): e0176872. doi:10.1371/journal.pone.0176872. http://dx.doi.org/10.1371/journal.pone.0176872Test.
مصطلحات موضوعية: Medicine and Health Sciences, Public and Occupational Health, Physical Activity, Survey Research, Questionnaires, Biology and Life Sciences, Physiology, Physiological Parameters, Body Weight, Body Mass Index, Engineering and Technology, Electronics, Accelerometers, Obesity, Social Sciences, Economics, Finance, Biological Locomotion, Walking, Sociology, Education, Schools
الوصف: Background: Illness-related absenteeism is a major threat to work productivity. Our objective was to assess the relationship between physical activity and unplanned illness-related absenteeism from work. Methods: We implemented physical activity program for sedentary non-clinician employees of a tertiary medical center. Financial rewards were available for reaching accelerometer-measured ambulatory physical activity goals over a 24-week period. We categorized participants into three groups based on mean levels of physical activity: low (0–74 min/week), medium (75–149 min/week) and meeting CDC guidelines (≥150 min/week). We built a multivariable Poisson regression model to evaluate the relationship between physical activity and rates of unplanned illness-related absenteeism. Results: The sample consisted of 292 employees who participated in the program. Their mean age was 38 years (SD 11), 83% were female, and 38% were obese. Over the 24 intervention weeks, participants engaged in a mean of 90 min/week (SD 74) of physical activity and missed a mean of 14 hours of work (SD 38) due to illness. Unplanned absenteeism due to illness was associated with physical activity. As compared to the group meeting CDC guidelines, in multivariable analyses those in the medium physical activity group had a 2.4 (95% CI 1.3–4.5) fold higher rate of illness-related absenteeism and those in the lowest physical activity group had a 3.5 (95% CI 1.7–7.2) fold higher rate of illness-related absenteeism. Discussion Less physical activity was associated with more illness-related absenteeism. Workforce-based interventions to increase physical activity may thus be a promising vehicle to reduce unplanned illness-related absenteeism.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417546/pdfTest/; PLoS ONE
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7دورية أكاديمية
المؤلفون: Messier, Stephen P., Callahan, Leigh F., Beavers, Daniel P., Queen, Kate, Mihalko, Shannon L., Miller, Gary D., Losina, Elena, Katz, Jeffrey N., Loeser, Richard F., Quandt, Sara A., DeVita, Paul, Hunter, David J., Lyles, Mary F., Newman, Jovita, Hackney, Betsy, Jordan, Joanne M.
المصدر: Messier, S. P., L. F. Callahan, D. P. Beavers, K. Queen, S. L. Mihalko, G. D. Miller, E. Losina, et al. 2017. “Weight-loss and exercise for communities with arthritis in North Carolina (we-can): design and rationale of a pragmatic, assessor-blinded, randomized controlled trial.” BMC Musculoskeletal Disorders 18 (1): 91. doi:10.1186/s12891-017-1441-4. http://dx.doi.org/10.1186/s12891-017-1441-4Test.
مصطلحات موضوعية: Osteoarthritis, Knee pain, Clinical trial, Pragmatic, Community based research
الوصف: Background: Recently, we determined that in a rigorously monitored environment an intensive diet-induced weight loss of 10% combined with exercise was significantly more effective at reducing pain in men and women with symptomatic knee osteoarthritis (OA) than either intervention alone. Compared to previous long-term weight loss and exercise trials of knee OA, our intensive diet-induced weight loss and exercise intervention was twice as effective at reducing pain intensity. Whether these results can be generalized to less intensively monitored cohorts is unknown. Thus, the policy relevant and clinically important question is: Can we adapt this successful solution to a pervasive public health problem in real-world clinical and community settings? This study aims to develop a systematic, practical, cost-effective diet-induced weight loss and exercise intervention implemented in community settings and to determine its effectiveness in reducing pain and improving other clinical outcomes in persons with knee OA. Methods/Design This is a Phase III, pragmatic, assessor-blinded, randomized controlled trial. Participants will include 820 ambulatory, community-dwelling, overweight and obese (BMI ≥ 27 kg/m2) men and women aged ≥ 50 years who meet the American College of Rheumatology clinical criteria for knee OA. The primary aim is to determine whether a community-based 18-month diet-induced weight loss and exercise intervention based on social cognitive theory and implemented in three North Carolina counties with diverse residential (from urban to rural) and socioeconomic composition significantly decreases knee pain in overweight and obese adults with knee OA relative to a nutrition and health attention control group. Secondary aims will determine whether this intervention improves self-reported function, health-related quality of life, mobility, and is cost-effective. Discussion Many physicians who treat people with knee OA have no practical means to implement weight loss and exercise treatments as recommended by numerous OA treatment guidelines. This study will establish the effectiveness of a community program that will serve as a blueprint and exemplar for clinicians and public health officials in urban and rural communities to implement a diet-induced weight loss and exercise program designed to reduce knee pain and improve other clinical outcomes in overweight and obese adults with knee OA. Trial registration clinicaltrials.gov Identifier: NCT02577549 October 12, 2015.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322619/pdfTest/; BMC Musculoskeletal Disorders
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8دورية أكاديمية
المؤلفون: Bassett, Ingrid V., Coleman, Sharon M., Giddy, Janet, Bogart, Laura M., Chaisson, Christine E., Ross, Douglas, Jacobsen, Margo M., Robine, Marion, Govender, Tessa, Freedberg, Kenneth A., Katz, Jeffrey N., Walensky, Rochelle P., Losina, Elena
المصدر: Bassett, I. V., S. M. Coleman, J. Giddy, L. M. Bogart, C. E. Chaisson, D. Ross, M. M. Jacobsen, et al. 2016. “Sizanani: A Randomized Trial of Health System Navigators to Improve Linkage to HIV and TB Care in South Africa.” Journal of Acquired Immune Deficiency Syndromes (1999) 73 (2): 154-160. doi:10.1097/QAI.0000000000001025. http://dx.doi.org/10.1097/QAI.0000000000001025Test.
مصطلحات موضوعية: health system navigator, linkage to HIV care, HIV/TB co-infection, South Africa
الوصف: Background: A fraction of HIV-diagnosed individuals promptly initiate antiretroviral therapy (ART). We evaluated the efficacy of health system navigators for improving linkage to HIV and tuberculosis (TB) care among newly diagnosed HIV-infected outpatients in Durban, South Africa. Methods: We conducted a randomized controlled trial (Sizanani Trial, NCT01188941) among adults (≥18 years) at 4 sites. Participants underwent TB screening and randomization into a health system navigator intervention or usual care. Intervention participants had an in-person interview at enrollment and received phone calls and text messages over 4 months. We assessed 9-month outcomes via medical records and the National Population Registry. Primary outcome was completion of at least 3 months of ART or 6 months of TB treatment for coinfected participants. Results: Four thousand nine hundred three participants were enrolled and randomized; 1899 (39%) were HIV-infected, with 1146 (60%) ART-eligible and 523 (28%) TB coinfected at baseline. In the intervention, 212 (39% of outcome-eligible) reached primary outcome compared to 197 (42%) in usual care (RR 0.93, 95% CI: 0.80 to 1.08). One hundred thirty-one (14%) HIV-infected intervention participants died compared to 119 (13%) in usual care; death rates did not differ between arms (RR 1.06, 95% CI: 0.84 to 1.34). In the as-treated analysis, participants reached for ≥5 navigator calls were more likely to achieve study outcome. Conclusions: ∼40% of ART-eligible participants in both study arms reached the primary outcome 9 months after HIV diagnosis. Low rates of engagement in care, high death rates, and lack of navigator efficacy highlight the urgency of identifying more effective strategies for improving HIV and TB care outcomes.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026386/pdfTest/; Journal of Acquired Immune Deficiency Syndromes (1999)
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9دورية أكاديمية
المصدر: Von Keudell, Arvind G., Thomas S. Thornhill, Jeffrey N. Katz, and Elena Losina. 2016. “Mortality Risk Assessment of Total Knee Arthroplasty and Related Surgery After Percutaneous Coronary Intervention.” The Open Orthopaedics Journal 10 (1): 706-716. doi:10.2174/1874325001610010706. http://dx.doi.org/10.2174/1874325001610010706Test.
مصطلحات موضوعية: Clopidogrel, Coronary stenting, Mortality, Plavix, Revision total knee arthroplasty, Total knee arthroplasty
الوصف: Background: The optimal antiplatelet therapy (APT) treatment strategy after Coronary Artery Stenting (CAS) in non-cardiac surgery, such as total knee arthroplasty (TKA) or urgent TKA-related surgery remains unknown. Methods: We built a decision tree model to examine the mortality outcomes of two alternative strategies for APT after CAS use in the perioperative period namely, continuous use and discontinuation. Results: If surgery was performed in the first month after CAS placement, discontinuing APT led to an estimated 30-day post TKA mortality of 10.5%, compared to 1.0% in a strategy with continuous APT use. Mortality with both strategies decreased with longer intervals. Conclusion: Our model demonstrated that APT discontinuation in patients undergoing TKA or urgent TKA related surgery after CAS placement might lead to greater 30-day mortality up to one year.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220172/pdfTest/; The Open Orthopaedics Journal
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10دورية أكاديمية
المؤلفون: Drain, Paul K., Losina, Elena, Coleman, Sharon M., Giddy, Janet, Ross, Douglas, Katz, Jeffrey N., Bassett, Ingrid V.
المصدر: Drain, Paul K., Elena Losina, Sharon M. Coleman, Janet Giddy, Douglas Ross, Jeffrey N. Katz, and Ingrid V. Bassett. 2016. “Rapid urine lipoarabinomannan assay as a clinic-based screening test for active tuberculosis at HIV diagnosis.” BMC Pulmonary Medicine 16 (1): 147. doi:10.1186/s12890-016-0316-z. http://dx.doi.org/10.1186/s12890-016-0316-zTest.
مصطلحات موضوعية: Tuberculosis, HIV/AIDS, Lipoarabinomannan (LAM), Urine, Diagnostic screening, South Africa
الوصف: Background: World Health Organization (WHO) recommends tuberculosis (TB) screening at HIV diagnosis. We evaluated the inclusion of rapid urine lipoarabinomannan (LAM) testing in TB screening algorithms. Methods: We enrolled ART-naïve adults who screened HIV-infected in KwaZulu-Natal, assessed TB-related symptoms (cough, fever, night sweats, weight loss), and obtained sputum specimens for mycobacterial culture. Trained nurses performed clinic-based urine LAM testing using a rapid assay. We used diagnostic accuracy, negative predictive value (NPV), and negative likelihood ratio, stratified by CD4 count, to evaluate screening for culture-positive TB. Results: Among 675 HIV-infected adults with median CD4 of 213/mm3 (interquartile range 85-360/mm3), 123 (18%) had culture-confirmed pulmonary TB. The WHO-recommended algorithm of any TB-related symptom had a sensitivity of 77% [95% confidence interval (CI) 69-84%] and NPV of 89% (95% CI 84-92%) for identifying active pulmonary TB. Including the LAM assay improved sensitivity (83%; 95% CI 75-89%) and NPV (91%; 95% CI 86-94%), while decreasing the negative likelihood ratio (0.45 versus 0.57). Among participants with CD4 < 100/mm3, including urine LAM testing improved the negative predictive value of symptom based screening from 83% to 87%. All screening algorithms with urine LAM performed better among participants with CD4 < 100/mm3, compared to those with CD4 ≥ 100/mm3. Conclusion: Clinic-based urine LAM screening increased the sensitivity of symptom-based screening by 6% among ART-naïve HIV-infected adults in a TB-endemic setting, thereby providing marginal benefit.
العلاقة: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109839/pdfTest/; BMC Pulmonary Medicine
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