Tanta University Hospital

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

RATIONALE: Corticosteroid therapy is commonly used among critically ill patients with Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients' clinical condition at the time of corticosteroid therapy initiation. OBJECTIVES: To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS. METHODS: ICU patients with MERs were included from 14 Saudi Arabian centers between September 2012 and October 2015. We performed marginal structural modeling to account for baseline and time-varying confounders. MEASUREMENTS AND MAIN RESULTS: Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (quartile 1 [Q1]-Q3, 1.0-7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141 of 151 [93.4%] vs. 121 of 158 [76.6%]; P < 0.0001) and had higher 90-day crude mortality (112 of 151 [74.2%] vs. 91 of 158 [57.6%]; P = 0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio, 0.75; 95% confidence interval, 0.52-1.07; P = 0.12) but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio, 0.35; 95% CI, 0.17-0.72; P = 0.005). CONCLUSIONS: Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies.

•Patients with cirrhosis experience high rates of hepatic decompensation and death following SARS-CoV-2 infection.•Mortality increased in stepwise fashion according to Child-Pugh class.•Other risk factors for death included advancing age and alcohol-related liver disease.•Mortality risk was higher in patients with advanced cirrhosis than propensity-score-matched controls without liver disease.•The majority of deaths in patients with cirrhosis were from COVID-19-related lung disease. Background & AimsChronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined.MethodsBetween 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network.ResultsMortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01–1.04), Child-Pugh A (OR 1.90; 1.03–3.52), B (OR 4.14; 2.4–7.65), or C (OR 9.32; 4.80–18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03–3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%–31.3%]) and C (+38.1% [27.1%–49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure.ConclusionsIn the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic.Lay summaryThis international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease. Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined. Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network. Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01–1.04), Child-Pugh A (OR 1.90; 1.03–3.52), B (OR 4.14; 2.4–7.65), or C (OR 9.32; 4.80–18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03–3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%–31.3%]) and C (+38.1% [27.1%–49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure. In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

OBJECTIVES: To conduct the first prospective, randomized, controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis (CRS). MATERIALS AND METHODS: Ninety patients with CRS were equally randomized either to medical or surgical therapy. All patients underwent pre- and posttreatment assessments of visual analogue score (VAS), the Sinonasal Outcome Test-20 (SNOT-20), the Short Form 36 Health Survey (SF-36), nitric oxide (NO), acoustic rhinometry, saccharine clearance time (SCT), and nasal endoscopy. Each patient had three assessments: before starting the treatment, after 6 months, and, finally, after 1 year. RESULTS: Both the medical and surgical treatment of CRS significantly improved almost all the subjective and objective parameters of CRS (P <.01), with no significant difference being found between the medical and surgical groups (P >.05), except for the total nasal volume in CRS (P <.01) and CRS without polyposis (P <.01) groups, in which the surgical treatment demonstrated greater changes. CONCLUSION: CRS should be initially targeted with maximal medical therapy (e.g., a 3 month course of a macrolide antibiotic, douche, and topical steroid), with surgical treatment being reserved for cases refractory to medical therapy. The presence of nasal polyps is not a poor prognostic factor for the efficacy of CRS therapy, either surgical or medical.

BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73-1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30-1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

BACKGROUND: Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers.This is an update of a Cochrane review first published in 2010, and previously updated in 2013. OBJECTIVES: To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. SEARCH METHODS: We searched the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 08 July 2016). We also searched 'Clinical Trials' on The Cochrane Library, MEDLINE, Embase and LILACS (date of the most recent search: 24 September 2015). SELECTION CRITERIA: Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. DATA COLLECTION AND ANALYSIS: Two authors selected relevant trials, assessed methodological quality and extracted data. MAIN RESULTS: Nine trials comparing either agalsidase alfa or beta in 351 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores measured by the Brief Pain Inventory severity, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval -3.79 to -0.41; at up to five months, mean difference -1.90 (95% confidence interval -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% confidence interval -3.66 to -0.34). There was a significant difference in the Brief Pain Inventory pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% confidence interval -3.92 to -0.28) but not at other time points. Death was not an outcome in either of the trials.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% confidence interval -2.09 to -1.31); heart, mean difference -0.90 (95% confidence interval -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% confidence interval -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only two trials compared agalsidase alfa to agalsidase beta. One of them showed no significant difference between the groups regarding adverse events, risk ratio 0.36 (95% confidence interval 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; (95% confidence interval 0.03 to 2.57).Two trials compared different dosing schedules of agalsidase alfa. One of them involved three different doses (0.2 mg/kg every two weeks; 0.1 mg/kg weekly and; 0.2 mg/kg weekly), the other trial evaluated two further doses to the dosage schedules: 0.4 mg/kg every week and every other week. Both trials failed to show significant differences with various dosing schedules on globotriaosylceramide levels. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores.One trial comparing agalsidase alfa to agalsidase beta showed no significant difference for any adverse events such as dyspnoea and hypertension.The methodological quality of the included trials was generally unclear for the random sequence generation and allocation concealment. AUTHORS' CONCLUSIONS: Trials comparing enzyme replacement therapy to placebo show significant improvement with enzyme replacement therapy in regard to microvascular endothelial deposits of globotriaosylceramide and in pain-related quality of life. There is, however, no evidence identifying if the alfa or beta form is superior or the optimal dose or frequency of enzyme replacement therapy. With regards to safety, adverse events (i.e., rigors, fever) were more significant in the agalsidase beta as compared to placebo. The long-term influence of enzyme replacement therapy on risk of morbidity and mortality related to Anderson-Fabry disease remains to be established. This review highlights the need for continued research into the use of enzyme replacement therapy for Anderson-Fabry disease.

The effects of rhinosinusitis treatment upon asthma are disputed. The first randomised prospective study of surgical compared with medical therapy of chronic rhinosinusitis in 90 patients with and without nasal polyps was previously reported. Asthma symptoms, control, forced expiratory volume in one second (FEV1), peak flow, exhaled nitric oxide, medication use and hospitalisation at 6 and 12 months from the start of the study were also monitored. This paper reports these results in 43 of those patients with concomitant asthma. Both medical and surgical treatment of chronic rhinosinusitis were associated with subjective and objective improvements in asthma. Overall asthma control improved significantly following both treatment modalities, but was better maintained after medical therapy, where improvement could also be demonstrated in the subgroup with nasal polyps. Medicine was superior to surgery with respect to a decrease in exhaled nitric oxide and increase in FEV1 in the polyp patients. Two patients noted worsening of asthma post-operatively. Improvement in upper airway symptoms, as assessed using a visual analogue scale, correlated with improvement in asthma symptoms and control. Treatment of chronic rhinosinusitis, medical or surgical, benefits concomitant asthma; that associated with nasal polyposis benefits more from medical therapy.

The COVID-19 pandemic is showing an exponential growth, mandating an urgent need to develop an effective treatment. Indeed, to date, a well-established therapy is still lacking. We aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) added to standard care in patients with COVID-19. This was a multicenter, randomized controlled trial conducted at three major university hospitals in Egypt. One hundred ninety-four patients with confirmed diagnosis of COVID-19 were included in the study after signing informed consent. They were equally randomized into two arms: 97 patients administrated HCQ plus standard care (HCQ group) and 97 patients administered only standard care as a control arm (control group). The primary endpoints were recovery within 28 days, need for mechanical ventilation, or death. The two groups were matched for age and gender. There was no significant difference between them regarding any of the baseline characteristics or laboratory parameters. Four patients (4.1%) in the HCQ group and 5 (5.2%) patients in the control group needed mechanical ventilation (P = 0.75). The overall mortality did not differ between the two groups, as six patients (6.2%) died in the HCQ group and 5 (5.2%) died in the control group (P = 0.77). Univariate logistic regression analysis showed that HCQ treatment was not significantly associated with decreased mortality in COVID-19 patients. So, adding HCQ to standard care did not add significant benefit, did not decrease the need for ventilation, and did not reduce mortality rates in COVID-19 patients.

BACKGROUND: Severe, intractable, chronic pain is a significant management problem for those involved in the long-term care of spinal cord injury (SCI) patients . Gabapentin, an anticonvulsant, is widely used for treating chronic pain. Ketamine, an NMDA receptor antagonist, has been available in clinical practice for 35 years. Its usefulness in pathological pain states is known. Despite this, no formal research on its effectiveness in treating neuropathic SCI pain exists. OBJECTIVES: This double-blind study sought to determine the safety and efficacy of adding a multi-day low dose ketamine infusion to oral gabapentin for treating chronic pain related to post spinal cord injury. STUDY DESIGN: Randomized, controlled, double blind trial. SETTING: Hospital, in-patient setting. METHODS: Forty patients diagnosed with neuropathic pain secondary to spinal cord injury were randomized into 2 equal groups. Group I received an 80 mg intravenous ketamine infusion diluted in 500 cc normal saline over a 5 hour period daily for one week and 300 mg of gabapentin 3 times daily. Group II received a placebo infusion and 300 mg of gabapentin 3 times daily (continued) after 300 mg of gabapentin 3 times daily. Using the visual analogue scale, pain was assessed prior to treatment, daily following ketamine or placebo infusions for 7 days, and then weekly for one month after infusion termination. Side effects, specifically those related to ketamine or gabapentin, were reported. RESULTS: Both groups demonstrated significantly reduced pain scores compared with pre-treatment values (P < 0.05). Group I showed significant pain score improvements over Group II at all measurements (P < 0.0001) during infusion and 2 weeks after infusion termination. There was no statistical difference between the groups at 3 weeks and 4 weeks after infusion termination (P = 0.54 and P = 0.25 respectively). Both drugs were tolerated by all patients; no side effects required intervention. CONCLUSION: Multi-day low dose ketamine infusion as adjuvant to gabapentin in post-spinal cord injury related chronic pain is safe and efficacious in reducing pain, but the effect compared to placebo ceased 2 weeks after infusion termination. LIMITATIONS: Study size limited to 40 patients.

BACKGROUND: Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. METHODS: Patients with MERS from 14 Saudi Arabian centers were included in this analysis. Patients who were initially managed with NIV were compared to patients who were managed only with invasive mechanical ventilation (invasive MV). RESULTS: Of 302 MERS critically ill patients, NIV was used initially in 105 (35%) patients, whereas 197 (65%) patients were only managed with invasive MV. Patients who were managed with NIV initially had lower baseline SOFA score and less extensive infiltrates on chest radiograph compared with patients managed with invasive MV. The vast majority (92.4%) of patients who were managed initially with NIV required intubation and invasive mechanical ventilation, and were more likely to require inhaled nitric oxide compared to those who were managed initially with invasive MV. ICU and hospital length of stay were similar between NIV patients and invasive MV patients. The use of NIV was not independently associated with 90-day mortality (propensity score-adjusted odds ratio 0.61, 95% CI [0.23, 1.60] P = 0.27). CONCLUSIONS: In patients with MERS and acute hypoxemic respiratory failure, NIV failure was very high. The use of NIV was not associated with improved outcomes.

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.

Although hepatocellular carcinoma (HCC) has been subjected to continuous investigation and its symptoms are well-known, early stage diagnosis of this disease remains difficult and the survival rate after diagnosis is typically very low (3-5%). Early and accurate detection of metabolic changes in the sera of patients with liver cirrhosis can help improve the prognosis of HCC and lead to a better understanding of its mechanism at the molecular level, thus providing patients with in-time treatment of the disease. In this study, we compared metabolite levels in sera of 40 HCC patients and 49 cirrhosis patients from Egypt by using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from cirrhotic controls are selected by statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. The identities of some of the putative identifications are verified by comparing their MS/MS fragmentation patterns and retention times with those from authentic compounds. Finally, the serum samples are reanalyzed for quantitation of selected metabolites as candidate biomarkers of HCC. This quantitation was performed using isotope dilution by selected reaction monitoring (SRM) on a triple quadrupole linear ion trap (QqQLIT) coupled to UPLC. Statistical analysis of the UPLC-QTOF data identified 274 monoisotopic ion masses with statistically significant differences in ion intensities between HCC cases and cirrhotic controls. Putative identifications were obtained for 158 ions by mass based search against databases. We verified the identities of selected putative identifications including glycholic acid (GCA), glycodeoxycholic acid (GDCA), 3β, 6β-dihydroxy-5β-cholan-24-oic acid, oleoyl carnitine, and Phe-Phe. SRM-based quantitation confirmed significant differences between HCC and cirrhotic controls in metabolite levels of bile acid metabolites, long chain carnitines and small peptide. Our study provides useful insight into appropriate experimental design and computational methods for serum biomarker discovery using LC-MS/MS based metabolomics. This study has led to the identification of candidate biomarkers with significant changes in metabolite levels between HCC cases and cirrhotic controls. This is the first MS-based metabolic biomarker discovery study on Egyptian subjects that led to the identification of candidate metabolites that discriminate early stage HCC from patients with liver cirrhosis.

BACKGROUND: The assessment of the response of chronic rhinosinusitis (CRS) to therapy is difficult. Computerized tomographic (CT) scans cannot be repeatedly used so measures such as symptom scores, endoscopic findings, and parallel measures such as saccharin clearance time are employed instead. OBJECTIVE: To study the effect of CRS therapy on nasal nitric oxide and to see whether nasal nitric oxide level changes correlate with other assessments. METHODS: The study was a prospective randomized trial of patients with CRS, with or without polyps, who had failed initial medical therapy with douching and nasal corticosteroids and who then had abnormal CT scans. They were treated either medically or surgically, with follow up at 6 and 12 months whilst still taking nasal corticosteroids. Nasal nitric oxide was measured initially and at 6 and 12 months as well as symptom scores, endoscopy, polyp grading, and saccharin clearance time. RESULTS: Initial absolute nasal nitric oxide levels correlated inversely with CT scan changes, (P<0.001). The percentage rise in nasal nitric oxide seen on both medical and surgical treatment correlated with changes in symptom scores (P<0.001), saccharin clearance time (P<0.001), endoscopic changes (P<0.001), polyp grades (P<0.05 at 6 months, P<0.01 at 12 months) and surgical scores (P<0.01). There was no significant correlation with age, sex, smoking or allergy. CONCLUSION: Nasal nitric oxide, which is easily measured, provides a valuable non-invasive objective measure of the response of CRS to therapy. Topical nasal corticosteroids may be needed to reduce the contribution of nasal epithelial nitric oxide and allow that emanating from the sinuses to be measured.

AIMS: The purpose of this study was to describe the clinical characteristics, management, and outcomes of acute heart failure (HF) patients from the Gulf acute heart failure registry (Gulf CARE). METHODS AND RESULTS: Data from 5005 HF patients admitted to 47 hospitals in seven Gulf countries during February to November 2012 were analysed. Fifty-five per cent of patients presented with acute decompensated chronic HF, while 45% had new-onset HF. Mean age was 59 ± 15 years, 63% were males, and 83% were Gulf citizens. Co-morbid conditions were hypertension (61%), diabetes mellitus (50%), CAD (47%), and atrial fibrillation or flutter (14%). The median LVEF was 35% (25-45%) with 69% presenting as HF with reduced EF (HFrEF). CAD was the most prevalent aetiology (53%) followed by idiopathic cardiomyopathy (18%), hypertensive heart disease (16%), and valvular heart disease (9%). At discharge, 71% and 78% of patients received beta-blockers and ACE inhibitors/ARBs, respectively. Use of coronary intervention and device therapy was <10%. In-hospital mortality was 6.3%. Re-hospitalization and cumulative mortality at 3 and 12 months were 18%/13% and 40%/20%, respectively. CONCLUSIONS: Gulf CARE results show that patients from this region are a decade younger than their Western counterparts, with a high prevalence of diabetes and HFrEF, and a lower prevalence of AF. Use of coronary intervention and device therapy was low, with high re-hospitalization rates. Short- and long-term mortality rates were similar to those of Western registries, but should be interpreted in the light of the younger age of Gulf CARE patients.

OBJECTIVES: Macrolides have been reported to be associated with improved outcomes in patients with viral pneumonia related to influenza and other viruses, possibly because of their immune-modulatory effects. Macrolides have frequently been used in patients with Middle East Respiratory Syndrome (MERS). This study investigated the association of macrolides with 90-day mortality and MERS coronavirus (CoV) RNA clearance in critically ill patients with MERS. METHODS: This retrospective analysis of a multicenter cohort database included 14 tertiary-care hospitals in five cities in Saudi Arabia. Multivariate logistic-regression analysis was used to determine the association of macrolide therapy with 90-day mortality, and the Cox-proportional hazard model to determine the association of macrolide therapy with MERS-CoV RNA clearance. RESULTS: Of 349 critically ill MERS patients, 136 (39%) received macrolide therapy. Azithromycin was most commonly used (97/136; 71.3%). Macrolide therapy was commonly started before the patient arrived in the intensive care unit (ICU) (51/136; 37.5%), or on day1 in ICU (53/136; 39%). On admission to ICU, the baseline characteristics of patients who received and did not receive macrolides were similar, including demographic data and sequential organ failure assessment score. However, patients who received macrolides were more likely to be admitted with community-acquired MERS (P=0.02). Macrolide therapy was not independently associated with a significant difference in 90-day mortality (adjusted odds ratio [OR]: 0.84; 95% confidence interval [CI] :0.47-1.51; P=0.56) or MERS-CoV RNA clearance (adjusted HR: 0.88; 95% CI:0.47-1.64; P=0.68). CONCLUSIONS: These findings indicate that macrolide therapy is not associated with a reduction in 90-day mortality or improvement in MERS-CoV RNA clearance.

Background Postoperative junctional ectopic tachycardia is one of the most serious arrhythmias that occur after pediatric cardiac surgery, difficult to treat and better to be prevented. Our aim was to assess the efficacy of prophylactic dexmedetomidine in preventing junctional ectopic tachycardia after pediatric cardiac surgery. Methods and Results A prospective controlled study was carried out on 90 children who underwent elective cardiac surgery for congenital heart diseases. Patients were randomized into 2 groups. Group I (dexmedetomidine group): 60 patients received dexmedetomidine; Group II (Placebo group): 30 patients received the same amount of normal saline intravenously. The primary outcome was the incidence of postoperative junctional ectopic tachycardia. Secondary outcomes included bradycardia, hypotension, vasoactive inotropic score, ventilation time, pediatric cardiac care unit stay, length of hospital stay, and perioperative mortality. The incidence of junctional ectopic tachycardia was significantly reduced in the dexmedetomidine group (3.3%) compared with the placebo group (16.7%) with P &lt;0.005. Heart rate while coming off cardiopulmonary bypass was significantly lower in the dexmedetomidine group (130.6±9) than the placebo group (144±7.1) with P &lt;0.001. Mean ventilation time, and mean duration of intensive care unit and hospital stay (days) were significantly shorter in the dexmedetomidine group than the placebo group ( P &lt;0.001). However, there was no significant difference between the 2 groups as regards mortality, bradycardia, or hypotension ( P &gt;0.005). Conclusion Prophylactic use of dexmedetomidine is associated with significantly decreased incidence of postoperative junctional ectopic tachycardia in children after congenital heart surgery without significant side effects.

Gut microbiota has a significant role in gut development, maturation, and immune system differentiation. It exerts considerable effects on the child's physical and mental development. The gut microbiota composition and structure depend on many host and microbial factors. The host factors include age, genetic pool, general health, dietary factors, medication use, the intestine's pH, peristalsis, and transit time, mucus secretions, mucous immunoglobulin, and tissue oxidation-reduction potentials. The microbial factors include nutrient availability, bacterial cooperation or antagonism, and bacterial adhesion. Each part of the gut has its microbiota due to its specific characteristics. The gut microbiota interacts with different body parts, affecting the pathogenesis of many local and systemic diseases. Dysbiosis is a common finding in many childhood disorders such as autism, failure to thrive, nutritional disorders, coeliac disease, Necrotizing Enterocolitis, helicobacter pylori infection, functional gastrointestinal disorders of childhood, inflammatory bowel diseases, and many other gastrointestinal disorders. Dysbiosis is also observed in allergic conditions like atopic dermatitis, allergic rhinitis, and asthma. Dysbiosis can also impact the development and the progression of immune disorders and cardiac disorders, including heart failure. Probiotic supplements could provide some help in managing these disorders. However, we are still in need of more studies. In this narrative review, we will shed some light on the role of microbiota in the development and management of common childhood disorders.

OBJECTIVE: To review our 15-year experience with ureteroscopic treatment of distal ureteric calculi and to determine the impact of improved technology and techniques on the efficacy, success and complications of the procedure. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 4512 patients who underwent 5133 ureteroscopic procedures for the treatment of distal ureteric calculi at our institution from January 1991 to December 2005. The patient and stone characteristics, treatment variables and clinical outcomes were assessed. Factors such as type of ureteroscope, procedure duration, procedure success, complication rate and hospital stay were evaluated. Data obtained from a cohort of patients that underwent the procedure from 1991 to 1995 (group 1) were statistical compared with those obtained from a cohort of patients from 1996 to 2005 (group 2). Logistic regression analysis was used to identify associated factors with the major complications of ureteroscopy. RESULTS: Overall, the stone-free rate after the procedure was 94.6%, the mean (sd; range) operative duration was 43 (15.0; 25-120) min, the intraoperative complication rate was 6.67%, the postoperative complication rate was 9.9%, and the mean (sd) hospital stay was 1.7 (1.1) days. The clinical and radiological follow-up (mean 36.8 months) for 71.3% of eligible patients detected only 12 ureteric strictures (0.23%). On comparing group 1 with group 2, the overall success of ureteroscopic stone extraction improved from 85.7% to 97.3% (P < 0.001), significant ureteric perforation decreased from 3.3% to 0.5% (P = 0.05), ureteric avulsion decreased from 1.3 to 0.1% (P < 0.05), ureteric stricture decreased from 0.7% to 0.1% (P < 0.007), the mean (sd) procedure time significantly decreased from 75 (42.9) min to 36.5 (12.5) min (P < 0.001), and the mean hospital stay significantly decreased from 2.5 (1.6) days to 0.5 (1.2) days, with a trend toward outpatient treatment. Logistic regression analysis showed a significant association of the major ureteroscopic complications with increased operative duration, type of ureteroscope used, stone impaction, stone size and surgeon experience. CONCLUSION: The present series shows the high success rate, with minor complications, that can be achieved with ureteroscopic treatment of distal ureteric calculi. Improvements in ureteroscope design, accessories, technique and experience have led to a significant increase in the success rate and decrease in the complication rate.

Researchers around the world are working at record speed to find the best ways to treat and prevent coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID-19 infected patients. This was a randomized open-label controlled study that included 164 patients with COVID-19. Patients were randomized into two groups where Group 1 (Ivermectin group) included patients who received ivermectin 12 mg once daily for 3 days with standard care and Group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay, and the need for mechanical ventilation. All patients were followed up for 1 month. Overall, 82 individuals were randomized to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had a shorter length of hospital stay (8.82 ± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant (p = 0.085). Three patients (3.7%) in each group required mechanical ventilation (p = 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups (p = 1.00). Although there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin-treated group.