The impact of unsupervised and unconsented switch of inhalers in patients with controlled asthma - A targeted literature review.

Inhaler combination formulations consisting of an inhaled corticosteroid (ICS) (fluticasone propionate) and a long-acting ß2 agonist (salmeterol xinafoate) are indicated as maintenance treatments for patients with asthma and/or for selected patients with chronic obstructive pulmonary disease. The emergence of generic equivalents to branded inhalers is expected to offer economic edge/savings; however, some may argue that cost advantages offered by generic inhalers may be offset by worsening outcomes due to improper inhaler use, reduced adherence, and consequently worse disease control. To understand how unsupervised and unconsented switch of dry-powder inhalers and/or metered-dose inhalers affects clinical and humanistic outcomes in asthma, comprehensive searches of Embase and MEDLINE were conducted to identify research articles published in the English language since 2011. Patients with asthma of any age who underwent an unsupervised and unconsented switch from an ICS/long-acting ß2 agonist to another (brand-to-generic or brand-to-brand) for non-medical reasons were the target of this research. Relevant outcomes included asthma control, medication adherence, and healthcare resource utilization. In total, 11 studies were identified for review (ten non-interventional and one post hoc); cohorts ranged from 19 to 42,553 patients. Six studies indicated that unsupervised and unconsented inhaler switch had a negative impact on asthma control; six studies indicated reduced medication adherence post-switching; and five studies reporting healthcare resource utilization showed it was unchanged or increased post-switching. Findings from this targeted review support concerns that unsupervised and unconsented inhaler switch has a largely negative impact on asthma-associated outcomes. Additional studies are warranted to further explore unsupervised and unconsented switch in asthma.

Common Prognostic Biomarkers and Outcomes in Patients with COVID-19 Infection in Saudi Arabia.

Background: COVID-19 is a respiratory disease that eventually became a pandemic, with 300 million people infected around the world. Alongside the improvement in COVID-19 management and vaccine development, identifying biomarkers for COVID-19 has recently been reported to help in early prediction and managing severe cases, which might improve outcomes. Our study aimed to find out if there is any correlation between clinical severity and elevated hematological and biochemical markers in COVID-19 patients and its effect on the outcome. Methods: We have collected retrospective data on socio-demographics, medical history, biomarkers, and disease outcomes from five hospitals and health institutions in the Kingdom of Saudi Arabia. Results: Pneumonia was the most common presentation of COVID-19 in our cohort. The presence of abnormal inflammatory biomarkers (D-dimer, CRP, troponin, LDH, ferritin, and t white blood cells) was significantly associated with unstable COVID-19 disease. In addition, patients with evidence of severe respiratory disease, particularly those who required mechanical ventilation, had higher biomarkers when compared to those with stable respiratory conditions (p < 0.001). Conclusion: Identifying biomarkers predicts outcomes for COVID-19 patients and may significantly help in their management.

Mycobacterium avium Complex Pulmonary Infection in a Patient With an SLC11A1 Mutation: A Rare Case Report and Review of Literature.

Mycobacterial avium complex (MAC) is one of the non-tuberculous mycobacterium (NTM) that is known to cause pulmonary disease (PD). MAC PD is diagnosed by fulfilling all of the following: presence of respiratory symptoms, imaging studies compatible with pulmonary disease, and isolation of the mycobacterium from either sputum or bronchial wash in symptomatic patients (isolation of at least two sputum specimens or at least one bronchial wash specimen). A mutation in the solute carrier family 11, member 1 (SLC11A1) gene has been associated with Mycobacteria infections, including MAC. Herein, we present a case of a young female diagnosed with pulmonary MAC who was found later to have an SLC11A1 genetic mutation.

Overprescription of short-acting ß2 -agonists among patients with asthma in Saudi Arabia: Results from the SABINA III cohort study.

Despite near-universal health care and timely updates to treatment guidelines in Saudi Arabia, asthma control remains suboptimal, warranting deeper exploration of its management practices. This study describes asthma characteristics and prescription patterns of short-acting ß2 -agonists (SABAs) in the Saudi Arabia cohort of the SABA use IN Asthma (SABINA) III study. Patients with asthma (aged ≥12 years) from seven sites across Saudi Arabia participated in this cross-sectional study. Asthma severity was classified by study investigators, guided by the 2017 Global Initiative for Asthma (GINA) recommendations. Of 511 patients enrolled, 502 patients, treated by respiratory medicine specialists, were analyzed (mean [standard deviation] age, 47.5 [14.8] years; female, 68.5%). Most patients had moderate-to-severe asthma (89.6%, GINA treatment steps 3-5), were overweight/obese (78.9%), and received full health care reimbursement (83.4%). Asthma was partially controlled/uncontrolled among 64.3% of patients; 62.3% experienced ≥1 severe asthma exacerbation(s), and 60.6% and 41.2% were prescribed ≥3 (overprescription) and ≥10 SABA canisters, respectively, in the 12 months preceding study initiation. Additionally, 21.9% of patients purchased SABA over the counter (OTC), of whom 66.4% purchased ≥3 SABA canisters. Ninety-seven (88.2%) patients who purchased SABA OTC also received SABA prescriptions, and 80.4% and 56.7% of these were prescribed ≥3 and ≥10 SABA canisters, respectively. Overall, compared with SABINA III, a higher percentage of patients from Saudi Arabia were overprescribed SABA (60.6% vs. 38.0%, respectively) and purchased SABA OTC (21.9% vs. 18.0%, respectively), underscoring the need to align asthma treatment practices with current evidence-based recommendations and regulate SABA OTC sales in Saudi Arabia.

Prevalence of depression and its associated factors among patients with confirmed COVID-19 in Makkah, Saudi Arabia.

Background: In early December 2019, a cluster of acute pneumonia of viral etiology had been identified in Wuhan, China. Later on, it has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing a worldwide pandemic. This pandemic triggered unprecedented health-related psychiatric sequalae. We aim in this study to evaluate the prevalence of depression and its associated factors among confirmed patients with COVID-19. Methodology: This is a cross-sectional study, we included adult patients more than 18 years old who have been diagnosed with PCR-confirmed COVID-19 and managed in a hospital, home, or hotel. A self-administered online questionnaire based on Patient Health Questionnaire (PHQ-9) Quick Depression Assessment questionnaire was used. Results: A total of 143 subjects completed the PHQ-9 questionnaire. The prevalence of moderate to severe depression was 34%. Prevalence of depression was positively associated with the female gender (p-value = 0.013). Location of COVID-19 management and financial status did not affect the prevalence of depression. Conclusion: The prevalence of depression among patients with COVID-19 is high, which underscores the importance of active screening and management of depression in this population.

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.

Childhood nephrolithiasis and nephrocalcinosis caused by metabolic diseases and renal tubulopathy: A retrospective study from 2 tertiary centers.

OBJECTIVES: To study childhood nephrolithiasis and nephrocalcinosis caused by metabolic disorders, distal renal tubular acidosis (dRTA), and familial hypomagnesemia, hypercalciuria, and nephrocalcinosis (FHHNC). METHODS: We retrospectively evaluated 86 children presented over 10 years (2011-2021), with nephrolithiasis (89%) and nephrocalcinosis (11%) caused by metabolic disorders (62%), FHHNC (21%), and dRTA (17%). RESULTS: The mean age at discovery was 72.7 months. The underlying metabolic etiologies included hyperoxaluria (38%), cystinuria (32%), hypercalciuria (24%), and hyperuricosuria (6%). Genetic testing was carried out for 23 patients. Hyperoxaluria was typically treated medically (75%). However, the majority progressed to end-stage kidney disease (ESKD). Most children with cystinuria, hypercalciuria, and hyperuricosuria required medical and surgical intervention. Patients with FHHNC typically presented with nephrocalcinosis. Genetic testing revealed Claudin-16 mutations in 7 children. Patients often progressed to stage II-IV chronic kidney disease (61%) and ESKD (6%). Patients with dRTA typically presented with nephrocalcinosis (80%), as well as poor weight gain and failure to thrive (86%), and medical treatment included sodium bicarbonate and potassium replacement. Despite nephrocalcinosis progression, most patients had normal renal function (53%), although the remaining 47% progressed to chronic kidney disease (none reached ESKD). CONCLUSION: Childhood nephrolithiasis is mainly related to metabolic disorders and is associated with poor renal outcomes. Nephrocalcinosis and nephrolithiasis have poor outcomes when associated with FHHNC, while nephrocalcinosis associated with dRTA has relatively good renal outcomes.

Outcome of Urinary Bladder Dysfunction in Children.

Bladder dysfunction in children is common, the most frequent underlying causes are neurologic bladder (NB), dysfunctional voiding syndrome (DVS), and the valve bladder syndrome (VBS). The aim of this study was to determine the 10-y survival rate and the associated morbidities in children with bladder dysfunction. One hundred ninety-nine children were included in the study; 60 with VBS, 75 DVS, and 64 NB. The mean age was 44 mo (CI: 37-50.9) and mean GFR 50.1 (CI 44.6-55.6) mL/min/1.73m2. The 10-y survival rate was 89%. Compared with patients with VBS, the mortality was 11 times higher among patients with NB (p = 0.02) but not significantly higher than patients with DVS (p = 0.2). GFR < 15 mL/min/1.73 m2 increases mortality rate by 6 times compared with normal GFR (p = 0.007). Late age at presentation (> 5 y) increases mortality risk and/or the need for renal replacement therapy (RRT) by almost 5 times (p = 0.013). It was concluded that the etiology of bladder dysfunction, baseline GFR, and the age at presentation significantly influence the survival rate and morbidities.

Treatment response among asthmatic patients with and without reversible airflow limitations.

OBJECTIVES: Asthma is a chronic airway disorder associated with variable airflow limitations, which are triggered by different stimuli. The reversibility of airflow limitations reflects patients' responses to the therapy with bronchodilators and improvements in airflow. This study aims to determine the treatment outcomes (improvements in forced expiratory volume in the first second (FEV1) and the number of asthma exacerbations) associated with the presence of airflow reversibility. METHODS: This retrospective cohort study included 154 adults (>18 years) who were diagnosed with asthma and had pulmonary function testing (PFT) at a tertiary care centre in KSA between January 1st, 2014 and May 31st, 2019. Smokers and patients with comorbidities or medications that could affect PFT were excluded from the analysis. Patients were classified as having a reversible airflow limitation when they exhibited a post-bronchodilator FEV1 increase of 12% and 200 mL. Exacerbations were defined as the need to use oral corticosteroids. Chi-square tests were used for comparative analyses. RESULTS: From our cohort, 42 patients exhibited reversibility. In contrast, 112 patients did not show any sign of reversibility. Asthmatics with baseline reversible airflow limitations experienced significant worsening of FEV1 during the follow-up period compared with those with no reversibility, showing a mean difference of 19.96 mL (p = 0.0206). There was no significant association between asthma reversibility and exacerbations (p = 0.23). CONCLUSION: In our study, during the follow-up of patients with asthma, we found that the reversibility of airflow was associated with significantly worse FEV1, although this did not have a significant effect on exacerbations. Therefore, we recommend regular spirometry follow-ups, particularly for patients with significant airway reversibility.

Factors That Influence Mortality in Critically Ill Patients with SARS-CoV-2 Infection: A Multicenter Study in the Kingdom of Saudi Arabia.

BACKGROUND: SARS-CoV-2 infection has a high mortality rate and continues to be a global threat, which warrants the identification of all mortality risk factors in critically ill patients. METHODS: This is a retrospective multicenter cohort study conducted in five hospitals in the Kingdom of Saudi Arabia (KSA). We enrolled patients with confirmed SARS-COV-2 infection admitted to any of the intensive care units from the five hospitals between March 2020 and July 2020, corresponding to the peak of recorded COVID-19 cases in the KSA. RESULTS: In total, 229 critically ill patients with confirmed SARS-CoV-2 infection were included in the study. The presenting symptoms and signs of patients who died during hospitalization were not significantly different from those observed among patients who survived. The baseline comorbidities that were significantly associated with in-hospital mortality were diabetes (62% vs. 48% among patients who died and survived (p = 0.046)), underlying cardiac disease (38% vs. 19% (p = 0.001)), and underlying kidney disease (32% vs. 12% (p < 0.001)). CONCLUSION: In our cohort, the baseline comorbidities that were significantly associated with in-hospital mortality were diabetes, underlying cardiac disease, and underlying kidney disease. Additionally, the factors that independently influenced mortality among critically ill COVID-19 patients were high Activated Partial Thromboplastin Time (aPTT )and international normalization ratio (INR), acidosis, and high ferritin.

Acute kidney injury in children with COVID-19: a retrospective study.

BACKGROUND: Acute kidney injury (AKI) is a complication of coronavirus disease 2019 (COVID-19). The reported incidence of AKI, however, varies among studies. We aimed to evaluate the incidence of AKI and its association with mortality and morbidity in children infected with severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) who required hospital admission. METHODS: This was a multicenter retrospective cohort study from three tertiary centers, which included children with confirmed COVID-19. All children were evaluated for AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition and staging. RESULTS: Of 89 children included, 19 (21 %) developed AKI (52.6 % stage I). A high renal angina index score was correlated with severity of AKI. Also, multisystem inflammatory syndrome in children (MIS-C) was increased in children with AKI compared to those with normal kidney function (15 % vs. 1.5 %). Patients with AKI had significantly more pediatric intensive care admissions (PICU) (32 % vs. 2.8 %, p < 0.001) and mortality (42 % vs. 0 %, p < 0.001). However, AKI was not associated with prolonged hospitalization (58 % vs. 40 %, p = 0.163) or development of MIS-C (10.5 % vs. 1.4 %, p = 0.051). No patient in the AKI group required renal replacement therapy. Residual renal impairment at discharge occurred in 9 % of patients. This was significantly influenced by the presence of comorbidities, hypotension, hypoxia, heart failure, acute respiratory distress, hypernatremia, abnormal liver profile, high C-reactive protein, and positive blood culture. CONCLUSIONS: AKI occurred in one-fifth of children with SARS-CoV-2 infection requiring hospital admission, with one-third of those requiring PICU. AKI was associated with increased morbidity and mortality, and residual renal impairment at time of discharge.

Coronavirus disease in children: A multicentre study from the Kingdom of Saudi Arabia.

BACKGROUND: The COVID-19 global pandemic caused by severe acute respiratory syndrome coronavirus 2 infection, warranted attention for whether it has unique manifestations in children. Children tend to develop less severe disease with a small percentage present with clinical manifestations of paediatric multisystem inflammatory syndrome and have poor prognosis. We studied the characteristics of COVID-19 in children requiring hospitalisation in the Kingdom of Saudi Arabia and assessed the clinical presentation and the risk factors for mortality, morbidity, and paediatric intensive care (PICU) admission. METHODS: We conducted a retrospective analysis of COVID-19 patients under 15 years hospitalised at three tertiary academic hospitals between 1 March and 30 June 2020. RESULTS: Eighty-eight children were enrolled (>20% were infants). Seven (8%) were in critical condition and required PICU admission, and 4 (4.5%) died of which 3 met the full diagnostic criteria of multi-system inflammatory syndrome and had a high Paediatric Risk of Mortality (PRISM) score at the time of admission. The initial polymerase chain reaction (PCR) test result was positive for COVID-19 in most patients (97.7%), and the remaining two patients had positive result in the repeated confirmatory test. In a subset of patients (20 subjects), repeated PCR testing was performed until conversion to negative result, and the average duration for conversion was 8 (95% CI: 5.2-10.5) days Children requiring PICU admission presented with signs of respiratory distress, dehydration, and heart failure. Most had fever (71.4%) and tonsillitis; 61.4% were discharged within 7 days of hospitalisation. Risk factors for mortality included skin rash, hypotension, hypoxia, signs of heart failure, chest radiograph suggestive of acute respiratory distress syndrome, anaemia, leucocytosis, hypernatraemia, abnormal liver enzymes, and high troponin I, and risk factors for prolonged hospitalisation (>7 days) included the presence of comorbidities, leucopaenia, hyponatraemia, and elevated C-reactive protein. CONCLUSIONS: The majority of hospitalised children had a brief febrile illness and made a full recovery, but a minority had severe disease.

The Clinical Course of COVID-19 Pneumonia in a 19-Year-Old Man on Intravenous Immunoglobulin Replacement Therapy for X-Linked Agammaglobulinemia.

BACKGROUND Since the emergence of coronavirus disease 2019 (COVID-19), patients with the illness have presented with considerable variation in severity. Some infected individuals present mild or no symptoms, while others present severe illness with some fatal outcomes. Multiple lines of management have been suggested for critically ill patients, such as intravenous immunoglobulin (IVIG) and steroids. IVIG is the main treatment for patients with X-linked agammaglobulinemia. Multiple studies have reported that these patients have excellent outcomes when they contract COVID-19. This report describes the clinical course of COVID-19 pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a 19-year-old man on IVIG replacement therapy for X-linked agammaglobulinemia (XLA). CASE REPORT A patient with XLA receiving a monthly dose of IVIG and having bronchiectasis managed by prophylactic azithromycin presented with fever, shortness of breath, productive cough, and diarrhea. He was admitted to our hospital with SARS-CoV-2 infection. His treatment course for COVID-19 was uncomplicated and had excellent results. He completed a 10-day course of piperacillin/tazobactam and his symptoms resolved 3 days after admission, without complications, oxygen supplementation, or intensive care unit admission. CONCLUSIONS Patients with XLA have weakened immunity and therefore may present with an infection as a first symptom. This report describes the mild course of COVID-19 pneumonia in an immunologically vulnerable patient with XLA who presented with SARS-CoV-2 infection while undergoing IVIG replacement therapy. Currently, IVIG is one of many supportive immune therapies undergoing clinical evaluation in patients with severe COVID-19.

Cinacalcet for Severe Secondary Hyperparathyroidism in Children with End-stage Kidney Disease.

Advanced chronic kidney disease with mineral and bone disorder have a significant obstacles to control serum bone profile [serum intact parathyroid hormone (iPTH), calcium and phosphorus] which subsequently have major effect on optimal bone strength, final adult height, and cardiovascular health. A retrospective, observational study, including a total of 36 children with end-stage kidney disease (ESKD). Fourteen children who were prescribed cinacalcet had been compared with the remaining 22 children who were managed with standard care. We report the efficacy and safety of cinacalcet for treatment of refractory secondary hyperparathyroidism (SHPT) in children with ESKD. After 6 months of cinacalcet treatment, the mean level of iPTH serum level decreased by 56% from 202 pmol/L [95% confidence interval (CI): 150-253] to 88 pmol/L (95% CI: 41-136), compared to the change observed in the control group (P <0.001). None of our patients reported serious adverse effects or developed hypocalcemia. Cinacalcet could be an effective and safe alternative to treat severe SHPT in children with ESKD. Further long-term and large-scale studies are necessary to confirm its safety and efficacy.

Comparison of Renal Stones and Nephrocalcinosis in Children: Findings From Two Tertiary Centers in Saudi Arabia.

Background: Renal stones (nephrolithiasis and urolithiasis) and nephrocalcinosis are uncommon in children; however, their incidences in pediatric populations have been increasing. Patients and Methods: This multicenter retrospective study compared the clinical presentation, etiology, and outcomes of childhood nephrolithiasis or urolithiasis with those of nephrocalcinosis. Results: The study included 144 children: 93 with renal stones and 51 with nephrocalcinosis. The mean age at presentation was 72 months and 54 months for children with renal stones and nephrocalcinosis, respectively. A history of consanguinity was found in 65% and 76% of the cases of renal stones and nephrocalcinosis, respectively. Congenital anomalies of the kidneys and urinary tract (CAKUT) were present in 28 and 9.8% of the patients with renal stones and nephrocalcinosis, respectively. The most common symptoms of renal stones were flank pain (29%), hematuria (15%), and dysuria (11%). Urinary tract infection was the primary presentation in the nephrocalcinosis group (18%), followed by failure to thrive (16%), polyuria (12%), and dehydration (12%). The majority of renal stone cases were caused by metabolic disorders, including hyperoxaluria (18%), cystinuria (18%), hypercalciuria (12%), and hyperuricosuria (2%). In contrast, the most common underlying disorders in cases of nephrocalcinosis were familial hypomagnesemia, hypercalciuria, nephrocalcinosis (35%), distal renal tubular acidosis (23%), and Bartter syndrome (6%). Clinical outcomes were significantly better in children with nephrolithiasis/urolithiasis than in those with nephrocalcinosis, who showed radiological evidence of worsening/persistent calcinosis and progressed more frequently to chronic kidney disease (stage II-IV) and end-stage kidney disease. Conclusion: The average age at presentation for children with renal stones was greater than that for those presenting with nephrocalcinosis. More than 25% of the children with renal stones were found to have CAKUT. Nephrocalcinosis was associated with worse clinical outcomes related to kidney function and disease resolution than nephrolithiasis.

Correlation Between the COVID-19 Respiratory Triage Score and SARS-COV-2 PCR Test.

Background: COVID-19 clinical presentation is usually non-specific and includes commonly encountered symptoms like fever, cough, nausea, and vomiting. It has been reported that COVID-19 patients can potentially transmit the disease to others before developing symptoms. Thus, extensive surveillance and screening of individuals at risk of the disease is required to limit SARS-COV-2 spread. The COVID-19 respiratory triage score has been used for patient screening. We aimed to determine its diagnostic performance characteristics, which have not been adequately studied before. Methodology: This is a retrospective observational study involving all patients screened for COVID-19 at a tertiary care facility. Patients were tested using nasopharyngeal swab for SARS-COV-2 PCR. The Saudi CDC COVID-19 respiratory triage score was measured for all subjects. The sensitivity, specificity, positive predictive value, and negative predicted value of COVID-19 respiratory triage score were measured with reference to SARS-COV-2 PCR test. Multivariate regression analysis was done to identify factors that can predict a positive SARS-COV-2 PCR test. Result: A total of 1,435 subjects were included. The COVID-19 respiratory triage score provided a marginal diagnostic performance with a receiver-operating characteristics (ROC) area under the curve value of 0.60 (95% CI: 0.57-0.64). A triage score of 5 provided the best cut-off value for the combined sensitivity and specificity. Clinical characteristics that independently predicted positive COVID-19 PCR test include male sex (adjusted OR: 1.47; p = 0.034), healthcare workers and their family members (adjusted OR: 1.99; 95%; p = 0.016), fever (adjusted OR: 2.98; p < 0.001), and moderate disease severity (adjusted OR: 5; p < 0.001). Conclusion: The current COVID-19 respiratory triage score has marginal diagnostic performance characteristics. Its performance can improve by including additional predictors to the respiratory symptoms in order to avoid missing COVID-19 patients with atypical presentation and to limit unnecessary SARS-COV-2 PCR testing.

Correction to: Short-term outcome associated with disease severity and electrolyte abnormalities among critically ill children with acute kidney injury.

Following publication of the original article [1].

Rituximab versus cyclophosphamide as first steroid-sparing agent in childhood frequently relapsing and steroid-dependent nephrotic syndrome.

BACKGROUND: Approximately 50% of children with steroid-sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications. METHODS: A prospective open-label non-randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia, or active infection. The recruited children were allocated either to the oral cyclophosphamide (3 mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months. RESULTS: Forty-six subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR 0.36; 95% CI 0.09-1.45; p = 0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N = 10) and 6.3 months in the rituximab group (N = 3). Both treatments were associated with a significant (p < 0.001) reduction in prescribed dose of oral alternate-day steroid from 1.02 to 0.36 mg/kg (cyclophosphamide) and 0.86 to 0.08 mg/kg (rituximab). Importantly, a significantly (p = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group. Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity besides severe leucopenia and neutropenia in the 7th week of treatment with complete recovery with the withdrawal of cyclophosphamide and maintenance of remission. A minor infusion-related reaction in the form of a generalized macular skin rash was observed in one patient (5%) in the rituximab group. CONCLUSIONS: Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide. Graphical abstract.

Incidence of latent tuberculosis infection among health science students during clinical training.

BACKGROUND: The prevalence of latent tuberculosis infection (LTBI) has been found to be high among students undergoing clinical training. The aim of this study is to determine the incidence of LTBI among undergraduate health science students after their clinical training and to compare the risk between different college specialties. METHODS: This is a retrospective cohort study of students who completed their clinical training from 2010 to 2017. The risk of LTBI was defined based on the conversion of tuberculin skin test (TST) results from negative at the start of training to positive after the completion of training. RESULTS: A total of 2000 students were evaluated, of whom 1997 were included in this analysis. Six percent tested positive in the first TST of the initial screening. Ten percent of students with a normal baseline TST converted to positive on the follow-up TST. Clinical training in the college of medicine increased the risk of LTBI by 76% (odds ratio: 1.76; 95% confidence interval: 1.04- 2.96; P = 0.03) compared to clinical training in other medical colleges. CONCLUSIONS: The risk of acquiring LTBI during clinical training in health science colleges is 10%. Students in the college of medicine are at significantly higher risk of LTBI than students of other health science specialties.

Short-term outcome associated with disease severity and electrolyte abnormalities among critically ill children with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) in critically ill children is associated with increased mortality and morbidity. In this study we evaluated the effect of AKI severity on the incidence of short-term mortality and morbidity. METHODS: Multicenter prospective cohort study was conducted over two years period. We used the Kidney Disease Improving Global Outcomes (KDIGO) to diagnose and stage AKI. RESULTS: A total of 511 out of 1367 included children (37.4%; 95% CI: 34.8-40.0) were diagnosed with AKI. They were categorized into three KDIGO stages: stage I (mild) in 47.5% (95% CI: 43.2-52.0), stage II (moderate) in 32.8% (95% CI: 28.8-37.1) and stage III (severe) in 19.7% (95% CI: 16.4-23.5). Stage II and III AKI had higher risk of mortality and longer length of stay (LOS) in hospital. Children with stage III AKI were more likely to require mechanical ventilation, referral to pediatric nephrology and discharge with abnormal creatinine level (above 100 uml\L). Hypervolemia, hypocalcemia, anemia, and acidosis were found to be independent risk factors of mortality. CONCLUSION: The extent of severity of AKI is directly associated with increased mortality, LOS and short-term morbidity.