Association and correlation of patient symptom perception and asthma control - a rapid literature review.

BACKGROUND: Several studies suggest that patients often under-estimate their asthma symptoms and over-estimate their level of asthma control, potentially putting them at risk of undertreatment with inhaled corticosteroids. OBJECTIVE: To determine the association and correlation between patient symptom perception and asthma control. METHODS: A rapid literature review comprising searches in MEDLINE, Embase and Cochrane Library identified English language articles published between 2011-2021 that included a statistical measure of the association or correlation between perceptions of symptoms and asthma control in patients with asthma (adults and/or children). [PROSPERO CRD42021230152]. The Joanna Briggs Institute (JBI) instrument was used for study quality appraisal. RESULTS: Of 22 identified studies, nine presented association data and 13 reported correlation analyses. Eight of nine association studies showed a discordance between patients perceived symptoms and level of asthma control or lung function; among these, patients more frequently overestimated their asthma control than they underestimated their asthma control. Of 10 studies reporting correlation coefficients, all reported a statistically significant correlation between increased symptoms and worse asthma control; however, the strength of the correlation was shown to be only weak or moderate in most studies (coefficients numerically ranged from 0.12 to 0.74). CONCLUSION: Many patients with asthma tend to overestimate their level of asthma control. Although more frequent or worse symptoms were shown to be statistically significantly correlated with worsening asthma control, there was wide variation in correlation strengths, most showing weak or moderate correlations. Research to further understand the reasons for patient symptom misperceptions are warranted.

The consequences of sleep deprivation on cognitive performance.

Although not fully understood, sleep is accepted as a vital and organized sequence of events that follows a regular cyclic program each night to ensure the human body can perform at its optimum. A lack of sleep, or sleep deprivation (SD), is a widespread phenomenon that can induce adverse changes in cognitive performance. This review focused on the biological explanation as well as the research investigating the numerous effects that SD can have on cognition. A reduction in sleep does not occur independently of the effects on memory, attention, alertness, judgment, decision-making, and overall cognitive abilities in the brain, resulting in decreased function and impaired cognitive performance.

Prevalence of eosinophilic, atopic, and overlap phenotypes among patients with severe asthma in Saudi Arabia: a cross-sectional study.

BACKGROUND: Eosinophilia is a significant factor in asthma severity; however, the prevalence of severe eosinophilic asthma in Saudi Arabia is largely unknown. We aimed to determine the prevalence of the eosinophilic (defined in this study as ≥ 300 cells/mm3 in blood), atopic (atopic phenotype 1, defined in this study as > 100 IU/mL total serum IgE; atopic phenotype 2, defined in this study as > 150 IU/mL), and overlap phenotypes among patients with severe asthma in Saudi Arabia. METHODS: A cross-sectional study was conducted in centers specialized in severe asthma management. Patients aged ≥ 12 years with severe asthma were enrolled. Study patients responded to the Global Initiative for Asthma 2018 assessment of asthma control questionnaire and provided study investigators with current information related to the study objectives. Additional medical record data and a blood sample for total serum IgE and complete blood count were collected. RESULTS: A total of 101 patients were enrolled; 83% were female and the mean (standard deviation) age was 48.7 (13.2) years. Forty-five (45%) patients had the eosinophilic phenotype, 50 (50%) had atopic phenotype 1, and 25 (25%) had phenotypic overlap (eosinophilic and atopic 1). Forty-one (41%) patients had atopic phenotype 2 and 23 (23%) had phenotypic overlap (eosinophilic and atopic 2). Asthma control and oral corticosteroid use patterns were similar and there were no significant differences in number of asthma exacerbations across phenotypes. CONCLUSIONS: In Saudi Arabia, 45% of patients with severe asthma had the eosinophilic phenotype, which is most likely an underestimation as no clinical features of eosinophilia were taken into account in the definition of eosinophilia. Approximately half of them had phenotypic overlap with the atopic phenotype. Trial registration NCT03931954; ClinicalTrials.gov, April 30, 2019.

Safety and Efficacy of Rifampin or Isoniazid Among People With Mycobacterium tuberculosis Infection and Living With Human Immunodeficiency Virus or Other Health Conditions: Post Hoc Analysis of 2 Randomized Trials.

BACKGROUND: The safety and efficacy of rifampin among people living with human immunodeficiency virus (PLHIV) or other health conditions is uncertain. We assessed completion, safety, and efficacy of 4 months of rifampin vs 9 months of isoniazid among PLHIV or other health conditions. METHODS: We conducted post hoc analysis of 2 randomized trials that included 6859 adult participants with Mycobacterium tuberculosis infection. Participants were randomized 1:1 to 10 mg/kg/d rifampin or 5 mg/kg/d isoniazid. We report completion, drug-related adverse events (AE), and active tuberculosis incidence among people living with HIV; with renal failure or receiving immunosuppressants; using drugs or with hepatitis; with diabetes mellitus; consuming >1 alcoholic drink per week or current/former smokers; and with no health condition. RESULTS: Overall, 270 (3.9%) people were living with HIV (135 receiving antiretroviral therapy), 2012 (29.3%) had another health condition, and 4577 (66.8%) had no condition. Rifampin was more often or similarly completed to isoniazid in all populations. AEs were less common with rifampin than isoniazid among PLHIV (risk difference, -2.1%; 95% confidence interval [CI], -5.9 to 1.6). This was consistent for others except people with renal failure or on immunosuppressants (2.1%; 95% CI, -7.2 to 11.3). Tuberculosis incidence was similar among people receiving rifampin or isoniazid. Among participants receiving rifampin living with HIV, incidence was comparable to those with no health condition (rate difference, 4.1 per 1000 person-years; 95% CI, -6.4 to 14.7). CONCLUSIONS: Rifampin appears to be safe and as effective as isoniazid across many populations with health conditions, including HIV. CLINICAL TRIALS REGISTRATION: NCT00170209; NCT00931736.

Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults.

BACKGROUND: A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects. METHODS: In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels. RESULTS: Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval [CI], -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events. CONCLUSIONS: The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).

Health System Costs of Treating Latent Tuberculosis Infection With Four Months of Rifampin Versus Nine Months of Isoniazid in Different Settings.

BACKGROUND: Four months of rifampin treatment for latent tuberculosis infection is safer, has superior treatment completion rates, and is as effective as 9 months of isoniazid. However, daily medication costs are higher for a 4-month rifampin regimen than a 9-month isoniazid regimen. OBJECTIVE: To compare health care use and associated costs of 4 months of rifampin and 9 months of isoniazid. DESIGN: Health system cost comparison using all health care activities recorded during 2 randomized clinical trials. (ClinicalTrials.gov: NCT00931736 and NCT00170209). SETTING: High-income countries (Australia, Canada, Saudi Arabia, and South Korea), middle-income countries (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea). PARTICIPANTS: Adults and children with clinical or epidemiologic factors associated with increased risk for developing tuberculosis that warranted treatment for latent tuberculosis infection. MEASUREMENTS: Health system costs per participant. RESULTS: A total of 6012 adults and 829 children were included. In both adults and children, greater health system use and higher costs were observed with 9 months of isoniazid than with 4 months of rifampin. In adults, the ratios of costs of 4 months of rifampin versus 9 months of isoniazid were 0.76 (95% CI, 0.70 to 0.82) in high-income countries, 0.90 (CI, 0.85 to 0.96) in middle-income countries, and 0.80 (CI, 0.78 to 0.81) in African countries. Similar findings were observed in the pediatric population. LIMITATION: Costs may have been overestimated because the trial protocol required a minimum number of follow-up visits, although fewer than recommended by many authoritative guidelines. CONCLUSION: A 4-month rifampin regimen was safer and less expensive than 9 months of isoniazid in all settings. This regimen could be adopted by tuberculosis programs in many countries as first-line therapy for latent tuberculosis infection. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Asthma control factors in the Gulf Cooperation Council (GCC) countries and the effectiveness of ICS/LABA fixed dose combinations: a dual rapid literature review.

BACKGROUND: Asthma control is influenced by multiple factors. These factors must be considered when appraising asthma interventions and their effectiveness in the Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and United Arab Emirates [UAE]). Based on published studies, the most prevalent asthma treatment in these countries are fixed dose combinations (FDC) of inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). This study is a rapid review of the literature on: (a) factors associated with asthma control in the GCC countries and (b) generalisability of ICS/LABA FDC effectiveness studies. METHODS: To review local factors associated with asthma control and, generalisability of published ICS/LABA FDC studies, two rapid reviews were conducted. Review 1 targeted literature pertaining to asthma control factors in GCC countries. Eligible studies were appraised, and clustering methodology used to summarise factors. Review 2 assessed ICS/LABA FDC studies in conditions close to actual clinical practice (i.e. effectiveness studies). Eligibility was determined by reviewing study characteristics. Evaluation of studies focused on randomised controlled trials (RCTs). In both reviews, initial (January 2018) and updated (November 2019) searches were conducted in EMBASE and PubMed databases. Eligible studies were appraised using the Critical Appraisal Skills Program (CASP) checklists. RESULTS: We identified 51 publications reporting factors associated with asthma control. These publications reported studies conducted in Saudi Arabia (35), Qatar (5), Kuwait (5), UAE (3), Oman (1) and multiple countries (2). The most common factors associated with asthma control were: asthma-related education (13 articles), demographics (11articles), comorbidities (11 articles) and environmental exposures (11 articles). Review 2 identified 61 articles reporting ICS/LABA FDC effectiveness studies from countries outside of the GCC. Of these, six RCTs were critically appraised. The adequacy of RCTs in informing clinical practice varied when appraised against previously published criteria. CONCLUSIONS: Asthma-related education was the most recurring factor associated with asthma control in the GCC countries. Moreover, the generalisability of ICS/LABA FDC studies to this region is variable. Hence, asthma patients in the region, particularly those on ICS/LABA FDC, will continue to require physician review and oversight. While our findings provide evidence for local treatment guidelines, further research is required in GCC countries to establish the causal pathways through which asthma-related education influence asthma control for patients on ICS/LABA FDC therapy.

Tuberculosis mortality and associated factors at King Abdulaziz Medical City Hospital.

BACKGROUND: Tuberculosis (TB) continues to be a public health challenge in Saudi Arabia, particularly for the elderly. This study was conducted to estimate mortality per 1000 person-year among TB and resistant TB cases and to identifying factors associated with mortality. METHODS: This is a retrospective cohort study of 713 new TB cases at King Abdulaziz Medical City in Riyadh diagnosed between January 1, 2000, and December 31, 2016. Patient medical records and microbiology lab databases were used to identify TB cases. Through reviews were conducted of patients' medical records, including physician notes, physical examinations, radiology (scans and imaging), laboratory tests, and follow-up notes. Collected data include demographic information, clinical features, diagnoses, comorbidities, and death rates. RESULTS: Of the 713 TB patients included in this study, 110 died, giving an average mortality rate of 22 per 1000 person-years (PY; 95% CI: 18.2-26.4). Elderly patients (≥ 60 years) had a higher mortality rate of 36.5 per 1000 PY (95% CI: 28.9-45.5). As age increases by one year, the hazard of mortality increase by 2.4% (aHR: 1.024 [95% CI: 1.009-1.039, P = 0.002]). Higher hazard of mortality was found among males (aHR: 2.014 [95% CI: 1.186-3.418, P = 0.010]). Patients with respiratory and other types of comorbidities and cancer had a higher mortality hazard (aHR: 1.898 [95% CI: 1.005-3.582, P = 0.048]; aHR: 2.346 [95% CI: 1.313-4.192, P = 0.004]; aHR: 3.292 [95% CI: 1.804-6.006, P = 0.001]), respectively. Multidrug-resistant TB (MDR-TB) was found in 2 cases (0.28%) (95% CI: 0.08-1.02), 1.68% were resistant to only one antibiotic, 0.14% had rifampicine-resistant TB (RR-TB), 0.28% had MDR-TB, and 0.14% had extensively drug-resistant TB (XDR-TB). CONCLUSIONS: The mortality rate among TB patients was found to be 22 per 1000 person-year at our center. TB was associated with high mortality rates among males, the elderly, and patients with cancer, respiratory illness, and other comorbidities. Future clinical practice should include establishing an efficient TB diagnostic program and continued hazard assessment of TB treatment options.

Rate and factors for scabies recurrence in children in Saudi Arabia: a retrospective study.

BACKGROUND: Despite the fact that several scabies outbreaks emerged in schools in Saudi Arabia in 2018, no study has investigated the risk of scabies recurrence among children in Saudi Arabia. This study aimed to estimate the rate of scabies recurrence and identify factors that were associated with an increased risk of recurrence among children. METHODS: This is a multi-center retrospective study of children (age < 14 years) who were diagnosed between May 20, 2015 and September 12, 2018 with one or multiple recurrent scabies at the Ministry of National Guard Health Affairs (MNGHA) hospitals and clinics in Saudi Arabia. Data were obtained from an electronic health system, BestCare database. RESULTS: A sample of 264 children analyzed (mean age of 6.7 years) resulted in a cumulative number of 316 scabies diagnoses in which 86 (27.2%) experienced scabies recurrence (at least once). Independent factors associated with a high risk of scabies recurrence: older children (adjusted hazard ratio [aHR], 1.036; 95% CI, 1.002-1.072; P = 0.039), female gender (aHR, 1.734; 95% CI, 1.329-2.262; P = 0.001), Western region of Saudi Arabia (aHR, 1.548; 95% CI, 1.115-2.151; P = 0.009), and 2nd tertile season [May to August] (aHR, 2.368; 95% CI, 1.706-3.288; P = 0.001). CONCLUSIONS: The study demonstrated that the recurrence rate of scabies among children is high. Older children, the female gender, the Western region of Saudi Arabia, and the seasonality were independently associated with an increased risk of scabies recurrence. High temperature and low humidity should be explored as leading factors for scabies infestations in Saudi Arabia. Findings derived from this study may be useful for clinicians and governments in optimizing clinical management of scabies cases and contacts.

Candida Bloodstream Infection: Changing Pattern of Occurrence and Antifungal Susceptibility over 10 Years in a Tertiary Care Saudi Hospital.

BACKGROUND: Candida has emerged as one of the most important pathogens that cause bloodstream infection (BSI).Understanding the current Candida BSI trends, the dominant species causing disease and the mortality associated with this infection are crucial to optimize therapeutic and prophylaxis measures. OBJECTIVES: To study the epidemiology and to evaluate the risk factors, prognostic factors, and mortality associated with candidemia and to compare these findings with previously published studies from Saudi Arabia. DESIGN: A retrospective medical record review. SETTING: Tertiary hospital in Riyadh. PATIENTS AND METHODS: The analysis included all cases of Candida blood stream infection who are >18 years old over the period from 2013 to 2018. Continuous variables were compared using the parametric T-test while categorical variables were compared using the Chi-squared test. MAIN OUTCOME MEASURE: Incidence, resistance, and hospital outcomes in Candida blood stream infection. SAMPLE SIZE: 324 patients. RESULTS: Three hundred and twenty-four episodes of Candida blood stream infections were identified. Median age of patients was 49.7 SD ± 28.1 years, and 53% of patients were males. More than half of the patients had an underlying disease involving the abdomen or laparotomy, 78% had an indwelling intravenous catheter, and 62% had suffered a bacterial infection within 2 weeks prior to candidemia. Candida albicans represents 33% of all isolates with decreasing trend overtime. There was an increase in the number of nonalbicans Candida overtime with Candida tropicalis in the lead (20%). Use of broad spectrum antibiotics (82%), prior ICU admission (60%) and use of central venous catheters (58%) were the most prevalent predisposing factors of candidemia. Azole resistance was variable overtime. Resistance to caspofungin remained very low (1.9%). Fourteen days crude mortality was 37% for ICU patients and 26.7% in non-ICU patients, while hospital crude mortality was 64.4% and 46.7%, respectively. CONCLUSION: There is an increasing trend of nonalbicans Candida blood stream infection. Fluconazole resistance remained low to C. albicans. Most isolates remain susceptible to caspofungin, voriconazole, and amphotericin B. Candida bloodstream infection is associated with high 14-day hospital mortality.

Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study.

AIMS: The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome - coronavirus (MERS-CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology. METHODS AND RESULTS: We analysed the post-mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T cell lymphoma, who acquired MERS-CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles. CONCLUSION: The results highlight the pulmonary and extrapulmonary pathological changes of MERS-CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS-CoV in kidney.

Emergency department 72-hour revisits among children with chronic diseases: a Saudi Arabian study.

BACKGROUND: Emergency Department (ED) revisits have often been used as an indicator of medical care quality. This study aimed to quantify the frequency of ED revisits within 72 h of discharge and identify its factors among children with chronic diseases. METHODS: We designed a retrospective cohort study of children with at least one chronic disease who were also under 18 years of age and had attended and were discharged from the ED at King Abdullah Specialist Children's Hospital (KASCH-RD), Riyadh, Saudi Arabia between April 19, 2015 and July 29, 2017. The outcome measure was the frequency of ED revisits during a period of 72 h after discharge. RESULTS: The study included 11,057 ED discharges of children with at least one chronic disease. Their revisit rate was 1211 (11%), with 83 (6.9%) having had a second ED revisit within 72 h of ED discharge. According to ICD-10 codes, the most common causes of ED revisits were respiratory, digestive, genitourinary, symptoms, and external causes. Factors of frequent ED revisits within 72 h were young age, institutional health insurance coverage, year of new health information system (2015), external causes, and genitourinary. CONCLUSION: The rate of 72-h ED revisits after discharge of children with chronic diseases treated at KASCH-RD was relatively high, and was associated with young age, institutional health insurance coverage, year of a new health information system implementation, and external causes of ED visit. These study findings amplify the need for intervention to reduce the rate of early ED revisits among children with chronic diseases.

The effects of age and gender on the prevalence of insomnia in a sample of the Saudi population.

OBJECTIVES: The aim of this study was to determine the prevalence of insomnia among the Saudi adult population. STUDY DESIGN: A cross-sectional insomnia survey was conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. The presence of insomnia was defined by difficulty initiating sleep, early morning awakening, or frequent awakening, in addition to the second-day effect in the form of fatigue, tiredness, or changes in the mode because of lack of sleep. RESULTS: The crude prevalence of insomnia was 77.7% (95% CI = 75.9-79.5%). The gender-adjusted prevalence of insomnia was higher for females, 88.7% (95% CI = 86.4-90.7%) than for males, 70.4% (95% CI = 67.8-72.9%), p-value = .001. The age-adjusted prevalence of insomnia was higher for the elderly, 93.7% (95% CI = 90.6-96.0%) than for the middle aged, 79.8% (95% CI = 77.4-82.1%), or for the young group, 64.2% (95% CI = 59.9-68.4%), p-value = .001. The Chi-square analyses revealed that (1) being elderly, widowed/divorced, females, or housewives, (2) having a lack of education, and (3) excessive tea consumption were significantly associated with elevated risks for insomnia (p-values < .05). CONCLUSIONS: Insomnia is most prevalent among Saudi females and the elderly Saudi population.

Risk factors hindering asthma symptom control in Saudi children and adolescents.

BACKGROUND: Maintaining good control of asthma symptoms can help to prevent exacerbations and its associated complications. The Asthma Control Test (ACT) can rapidly assess the effectiveness of asthma management plan and therapy. The aim of this study was therefore to identify risk factors associated with uncontrolled asthma symptoms in young Saudi asthmatic children (3-17 years old). METHODS: In this cross-sectional hospital-based survey, the ACT was administered to 297 asthmatic children/adolescents, recruited at the emergency department (ED) of two major hospitals. RESULTS: Most recruited patients had intermittent (63.5%) and mild persistent (27.6%) asthma; few had moderate persistent (8.9%) and none had severe asthma. These patients visited the ED four times (3.9 ± 3.2), on average. Almost half of the patients stated that they had not received education about asthma (47%) or education about medication use (43%). Most patients (60.3%) had uncontrolled symptoms (ACT score ≤19), of whom the intermittent asthma patients had better scores than those with more severe symptoms. Children ≤6 years old, with symptoms diagnosed <5 years previously and who were not attending school, had significantly worse control than older patients. Poor medication compliance and inappropriate inhaler device use were ascribed to younger patients (<12 years old) and worse scores; particularly in relation to stopping inhaled corticosteroid therapy when their symptoms improve. Patients with poor control also stated that they had not received education about inhaler device use. CONCLUSIONS: Most Saudi asthmatic children/adolescents visiting the ED had poor control of symptoms; indeed, none achieved complete control, which is related to deficient medication compliance and improper medication inhaler device use; deficient knowledge about asthma was also another factor hindering control.

Pulmonary embolism versus pulmonary vasculitis in Hughes-Stovin syndrome: Characteristic computed tomography pulmonary angiographic findings and diagnostic and therapeutic implications. HSS International Study Group.

BACKGROUND AND AIM: Hughes-Stovin syndrome (HSS) is a rare systemic vasculitis with widespread venous/arterial thrombosis and pulmonary vasculitis. Distinguishing between pulmonary embolism (PE) and in-situ thrombosis in the early stages of HSS is challenging. The aim of the study is to compare clinical, laboratory, and computed tomography pulmonary angiography (CTPA) characteristics in patients diagnosed with PE versus those with HSS. METHODS: This retrospective study included 40 HSS patients with complete CTPA studies available, previously published by the HSS study group, and 50 patients diagnosed with PE from a single center. Demographics, clinical and laboratory findings, vascular thrombotic events, were compared between both groups. The CTPA findings were reviewed, with emphasis on the distribution, adherence to the mural wall, pulmonary infarction, ground glass opacification, and intra-alveolar hemorrhage. Pulmonary artery aneurysms (PAAs) in HSS were assessed and classified. RESULTS: The mean age of HSS patients was 35 ± 12.3 years, in PE 58.4 ± 17 (p < 0.0001). Among PE 39(78 %) had co-morbidities, among HSS none. In contrast to PE, in HSS both major venous and arterial thrombotic events are seen.. Various patterns of PAAs were observed in the HSS group, which were entirely absent in PE. Parenchymal hemorrhage was also more frequent in HSS compared to PE (P < 0.001). CONCLUSION: Major vascular thrombosis with arterial aneurysms formation are characteristic of HSS. PE typically appear loosely-adherent and mobile whereas "in-situ thrombosis" seen in HSS is tightly-adherent to the mural wall. Mural wall enhancement and PAAs are distinctive pulmonary findings in HSS. The latter findings have significant therapeutic ramifications.

Eosinophils induce airway smooth muscle cell proliferation.

Asthma is characterized by eosinophilic airway inflammation and remodeling of the airway wall. Features of airway remodeling include increased airway smooth muscle (ASM) mass. However, little is known about the interaction between inflammatory eosinophils and ASM cells. In this study, we investigated the effect of eosinophils on ASM cell proliferation. Eosinophils were isolated from peripheral blood of mild asthmatics and non-asthmatic subjects and co-cultured with human primary ASM cells. ASM proliferation was estimated using Ki-67 expression assay. The expression of extracellular matrix (ECM) mRNA in ASM cells was measured using quantitative real-time PCR. The role of eosinophil derived Cysteinyl Leukotrienes (CysLTs) in enhancing ASM proliferation was estimated by measuring the release of leukotrienes from eosinophils upon their direct contact with ASM cells using ELISA. This role was confirmed either by blocking eosinophil-ASM contact or co-culturing them in the presence of leukotrienes antagonist. ASM cells co-cultured with eosinophils, isolated from asthmatics, but not non-asthmatics, had a significantly higher rate of proliferation compared to controls. This increase in ASM proliferation was independent of their release of ECM proteins but dependent upon eosinophils release of CysLTs. Eosinophil-ASM cell to cell contact was required for CysLTs release. Preventing eosinophil contact with ASM cells using anti-adhesion molecules antibodies, or blocking the activity of eosinophil derived CysLTs using montelukast inhibited ASM proliferation. Our results indicated that eosinophils contribute to airway remodeling during asthma by enhancing ASM cell proliferation and hence increasing ASM mass. Direct contact of eosinophils with ASM cells triggers their release of CysLTs which enhance ASM proliferation. Eosinophils, and their binding to ASM cells, constitute a potential therapeutic target to interfere with the series of biological events leading to airway remodeling and Asthma.

Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils.

BACKGROUND: Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-ß and IL-11, however, the mechanism regulating this process is not fully understood. OBJECTIVE: In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines. METHODS: Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-ß and IL-11 was determined using real time PCR and ELISA assays. RESULTS: The basal expression levels of eosinophil derived TGF-ß and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-ß and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release. CONCLUSIONS: Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.

CC and CXC chemokines induce airway smooth muscle proliferation and survival.

The increase in airway smooth muscle (ASM) mass is a major structural change in asthma. This increase has been attributed to ASM cell (ASMC) hyperplasia and hypertrophy. The distance between ASMC and the epithelium is reduced, suggesting migration of smooth muscle cells toward the epithelium. Recent studies have suggested a role of chemokines in ASMC migration toward the epithelium; however, chemokines have other biological effects. The objective of the current study is to test the hypothesis that chemokines (eotaxin, RANTES, IL-8, and MIP-1α) can directly influence ASMC mass by increasing the rate of proliferation or enhancing the survival of these cells. Human ASMCs were exposed to different concentrations of eotaxin, RANTES, IL-8, or MIP-1α. To test for proliferation, matched control and stimulated ASMC were pulsed with [(3)H]thymidine, or ASMCs were stained with BrdU and then analyzed with flow cytometry. Apoptosis was measured using Annexin V staining and flow cytometry. Expression of phosphorylated p42/p44 and MAPKs was assessed by Western blot. In a concentration-dependent manner, chemokines including eotaxin, RANTES, IL-8, and MIP-1α increased ASMC's [(3)H]thymidine incorporation and DNA synthesis. IL-8, eotaxin, and MIP-1α decreased the rate of apoptosis of ASMCs compared with the matched controls. A significant increase in phosphorylated p42/p44 MAPKs was seen after treating ASMCs with RANTES and eotaxin. Moreover, inhibition of p42/p44 MAPK phosphorylation reduced the level of chemokine-induced ASM proliferation. We conclude that chemokines might contribute to airway remodeling seen in asthma by enhancing the number and survival of ASMCs.

Advance medical directives: a proposed new approach and terminology from an Islamic perspective.

Advance directives are specific competent consumers' wishes about future medical plans in the event that they become incompetent. Awareness of a patient's autonomy particularly, in relation to their right to refuse or withdraw treatment, a right for the patient to die from natural causes and interest in end of life issues were among the main reasons for developing and legalizing advance medical directives in developed countries. However, in many circumstances cultural and religious aspects are among many factors that can hamper implementation of advance directives. Islam and Muslims in general have a good understanding of death and dying. Islam allows the withholding or withdrawal of treatments in some cases where the intervention is considered futile. However, there is lack of literature and debate about such issues from an Islamic point of view. This article provides the Islamic perspective with regards to advance medical directive with the hope that it will generate more thoughts and evoke further discussion on this important topic.

A survival analysis of idiopathic pulmonary fibrosis in the context of antifibrotic therapy in Saudi Arabia.

BACKGROUND: The prognosis of idiopathic pulmonary fibrosis (IPF) can be predicted by the gender, age, and physiology (GAP) index. However, antifibrotic therapy (i.e., nintedanib and pirfenidone) may improve survival. AIMS: This study aimed to compare the outcomes of antifibrotic-treated IPF with the survival predicted by the GAP index. METHODS: A retrospective cohort study was conducted from March 2014 to January 2020. The electronic health-care records of all IPF patients treated with nintedanib or pirfenidone were reviewed. Besides standard demographic and mortality data, the variables required to calculate the GAP index were also extracted. RESULTS: Eighty-one patients (male 55, 68%; age 71.4 ± 10.2 years) with IPF received antifibrotic therapy (nintedanib 44.4%; pirfenidone 55.6%; mean follow-up 35 ± 16.5 months). Cumulative mortality (whole cohort 3 years 12%; 4 years 26%; 5 years 33%) was significantly less than predicted by the GAP index. CONCLUSIONS: The survival of antifibrotic-treated IPF is better than predicted by the GAP index. Novel systems for prognostication are required. The survival benefit from pirfenidone and nintedanib seem similar overall.