Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, ...treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health.
Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.
Several recent studies have documented an increased incidence of newly diagnosed type 1 Diabetes (T1D) cases in children and adolescents during the COVID-19 pandemic and a more severe presentation at ...diabetes onset. In this descriptive study, we present the experience of the Diabetes Centre of the Division of Endocrinology, Diabetes, and Metabolism of the First Department of Pediatrics of the National and Kapodistrian University of Athens Medical School at "Aghia Sophia" Children's Hospital in Athens, Greece, concerning new cases of T1D diagnosis during the COVID-19 pandemic (March 2020- December 2021). Patients who had already been diagnosed with T1D and needed hospitalization due to poor control during the pandemic have been excluded from this study. Eighty- three children and adolescents with a mean age of 8,5 ± 4.02 years were admitted to the hospital due to newly diagnosed T1D during this 22 months' period in comparison to 34 new cases in the previous year. All patients admitted during the pandemic with a new diagnosis of T1D, presented in their majority with DKA (Ph: 7.2) representing an increase of new severe cases in comparison to previous years (Ph 7.2 versus 7.3, p value: 0.021, in the previous year), p-value: 0.027. 49 cases presented with DKA, of which 24 were characterized moderate and 14 severe DKA (28.9% and 16,9%, respectively), while 5 patients newly diagnosed, needed to be admitted to the ICU to recover from severe acidosis. Whether a previous COVID- 19 infection could have been the triggering factor is not supported by the SARS-Cov2 specific antibodies analysis in our cohort of patients. As far as HbA1c is concerned there was no statistically significant difference between the pre COVID-19 year and the years of the pandemic (11.6% versus 11.9%, p- value: 0.461). Triglycerides values were significantly higher in patients with new onset T1D during COVID-19 years compared to those before the pandemic (p value= 0.032). Additionally, there is a statistically significant correlation between Ph and Triglycerides for the whole period 2020-2021 (p-value<0.001), while this correlation is not significant for the year 2019. More large- scale studies are required to confirm these observations.
IntroductionClinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to ...treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.Methods and analysisStandard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.Ethics and disseminationEthics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.PROSPERO registration numbersCRD42020132990, CRD42020171624.
The role of sarcopenia and sarcopenic obesity in patients with pancreatic ductal adenocarcinoma(PDAC) remains controversial.
Medline and Web of Science were searched for studies reporting survival in ...sarcopenic and/or sarcopenic obese patients with pancreatic cancer. Primary outcome was mortality in patients with sarcopenia and/or sarcopenic obesity versus non-sarcopenic and/or non-sarcopenic obese patients. Secondary outcome was the incidence of major postoperative complications.
Eleven studies comprising 2.297 patients were considered suitable for inclusion. Overall 959 of 2.111(45.4%) patients were defined as sarcopenic and 163 of 1.254(13%) as sarcopenic obese. Patients’ age was above 60 years(range 63-69) with a male proportion ranging from 50.8% to 68.0%. Of 2.297 patients, 958(41.7%) underwent palliative treatment, 1.339(58.3%) curative resections. Follow-up ranged from 11 to 57.7 months. Median overall survival ranged from 4.3 to 12 months in palliative patients and 17.4 to 25.8 months after curative resection. Overall proportions of sarcopenic patients varied from 21.3% to 65.3%. Sarcopenia was significantly associated with poorer overall survival(HR 1.49; 95%CI 1.27-1.74,p<0.001). Sarcopenic obesity was reported in 0.6% to 25.0% of patients, and was also significantly associated with poorer overall survival(HR 2.01; 95%CI 1.55-2.61,p<0.001). The incidence of major complications ranged from 8.6% to 33.9%. Rates of clinically relevant(grade B/C) postoperative pancreatic fistulas varied from 8.3% to 17.8%. Sarcopenic obesity was an independent predictor of major postoperative complications in one study, in another study sarcopenia was significantly associated with clinically relevant pancreatic fistulas.
Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with PDAC.
•This meta-analysis assesses the role of sarcopenia and sarcopenic obesity in patients with pancreatic ductal adenocarcinoma(PDAC).•Primary outcome was mortality, secondary outcome was the incidence of major postoperative complications.•Sarcopenia was significantly associated with poorer overall survival(HR 1.48; 95%CI 1.26-1.74,p<0.001).•Sarcopenic obesity was also significantly associated with poorer overall survival(HR 2.01; 95%CI 1.55-2.61,p<0.001).•Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with PDAC.
Abstract Purpose The relative effectiveness and tolerability of treatments for type 2 diabetes mellitus (T2DM) is not well understood because few randomized, controlled trials (RCTs) have compared ...these treatments directly. The purpose of the present study was to evaluate the relative effectiveness and tolerability of treatments of T2DM. Methods We performed a network meta-analysis of available RCTs with pharmacologic interventions in T2DM and compared antidiabetic drugs and combination regimens with metformin (the reference drug). Glycemic control (proportion achieving HbA1c goal) and tolerability (risk of hypoglycemia) were the primary outcomes of interest. Direct and indirect relative effects (unadjusted) were expressed as odds ratios and 95% CIs. Findings Eight treatments (glucagon-like peptide-1 GLP-1 agonists plus metformin, sulfonylureas plus metformin, dipeptidyl peptidase-4 DPP-4 inhibitors plus metformin, colesevelan plus metformin, thiazolidinediones plus metformin, meglitinides plus metformin, α-glucosidase inhibitor plus metformin, and rosiglitazone monotherapy) outperformed metformin (direct effects). Triple combinations of GLP-1, thiazolinedione, insulin, metiglinide, or sulfonylureas added to a metformin backbone improved glycemic control (indirect effects). Higher risk of hypoglycemia was noted for sulfonylureas, α-glycosidases, and metiglinides when added to metformin (direct effects). Across indirect effects, only 17% of comparisons yielded less risk of hypoglycemia (70% were worse and 13% were comparable). Implications Our results point out the relative superiority of 2- and 3-drug combination regimens over metformin and summarize treatment effects and tolerability in a comprehensive manner, which adds to our knowledge regarding T2DM treatment options.
Abstract Background: The use of dopamine agonists (DAs) for the treatment of restless legs syndrome (RLS) has been assessed in numerous randomized clinical trials (RCTs). Objectives: The aims of this ...study were to assess the reporting quality of published RCTs according to the Consolidated Standards of Reporting Trials (CONSORT) statement and to synthesize the study results in terms of efficacy and tolerability to inform the clinical management of RLS. Methods: PubMed and Cochrane Controlled Trials Register were searched for English-language RCTs that assessed the effects of DAs in RLS. Quality of reporting was measured using the proportion of 17 CONSORT checklist items included in each study. The 2 primary outcomes were pooled mean change from baseline in International RLS (IRLS) Study Group rating scale score (Δμ) (95% CI) and relative risk (RR) (95% CI) of response based on the Clinical Global Impression-Improvement (CGI-I) scale score. The pooled proportions of adverse events (PAEs) (95% CI) were also estimated. Results: Eighteen RCTs (N = 2848 patients) were included. Two of the 17 CONSORT checklist items were reported in 7 studies (39%) and 9 of the 17 items were reported in all 18 studies (100%). The differences in the IRLS scores and RR for CGI-I were significantly greater with pramipexole, ropinirole, rotigotine, and cabergoline compared with placebo. Results for heterogeneity were nonsignificant. The difference in Δμ (95% CI) was significant with pramipexole (−6.63 −9.15 to −4.10) versus ropinirole (−3.64 −4.76 to 2.51) (P = 0.04). The difference between pramipexole and rotigotine was nonsignificant. The pooled PAEs (95% CI) for pramipexole, ropinirole, and rotigotine were 4.8% (2.0% to 8.7%), 10.2% (2.6% to 22.1%), and 7.6% (1.3% to 18.5%), respectively. In the trial of sumanirole, the PAE value was 2% (0% to 5.4%). Conclusion: Based on the findings from the meta-analysis, DAs were significantly more efficacious in the treatment of RLS compared with placebo.
Background
Gastrojejunostomy (GJ) and self-expanding metal stents (SEMS) are the two most common palliative treatment options for patients with malignant gastric outlet obstruction (GOO). Randomised ...trials and retrospective studies have shown discrepant results, so that there is still a controversy regarding the optimal treatment of GOO.
Methods
Medline, Web of Science and Cochrane Library were systematically searched for studies comparing GJ to SEMS in patients with malignant GOO. Primary outcomes were survival and postoperative mortality. Secondary outcomes were frequency of re-interventions, major complications, time to oral intake and length of hospital stay.
Results
Twenty-seven studies, with a total of 2.354 patients, 1.306 (55.5%) patients in the SEMS and 1.048 (44.5%) patients in the GJ group, were considered suitable for inclusion. GJ was associated with significantly longer survival than SEMS (mean difference 43 days, CI 12.00, 73.70,
p
= 0.006). Postoperative mortality (OR 0.55, CI 0.27, 1.16,
p
= 0.12) and major complications (OR 0.73, CI 0.5, 1.06,
p
= 0.10) were similar in both groups. The frequency of re-interventions, however, was almost three times higher in the SEMS group (OR 2.95, CI: 1.70, 5.14,
p
< 0.001), whereas the mean time to oral intake and length of hospital stay were shorter in the SEMS group (mean differences − 5 days, CI − 6.75, − 3.05 days,
p
< 0.001 and − 10 days, CI − 11.6, − 7.9 days,
p
< 0.001, respectively).
Conclusions
Patients with malignant GOO and acceptable performance status should be primarily considered for a palliative GJ rather than SEMS.
Purpose
The aim of this study was to evaluate the efficacy of vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis and to identify possible risk factors of ...fistula formation.
Methods
The hospital OPS-database (time period 2005–2014) was searched to identify patients treated with an open abdomen due to secondary peritonitis, who underwent vacuum-assisted closure therapy. Medical records were retrospectively analyzed for patients’ characteristics, cause of peritonitis, duration of vacuum therapy, number of relaparotomies, fascial closure rates, and risk factors of fistula formation.
Results
Forty-three patients (19 male, 24 female) with a median age of 65 years (range 24–90 years) were identified. The major cause of secondary peritonitis was anastomotic leakage after intestinal anastomosis or bowel perforation, the median APACHE II score was 11. Median duration of VAC treatment was 12 days (range 3–88 days). Twenty of 43 (47 %) patients died from septic complications. Delayed fascial closure was obtained by suturing in 20 of 43 patients (47 %). Overall 16 of 43 (37 %) patients developed enteroatmospheric fistulas. Re-explorations after starting VAC treatment and duration of VAC therapy were significantly associated with the occurrence of enteroatmospheric fistulas (
p
< 0.001). ROC curve analysis determined the optimal duration of VAC therapy to reduce the risk of fistula formation at 13 days.
Conclusions
Long-term VAC treatment of patients with an open abdomen due to secondary peritonitis results in a relatively low fascial closure rate and a high risk of fistula formation.
Wheezing is the cardinal symptom of asthma; its presence early in life, mostly caused by viral infections, is a major risk factor for the establishment of persistent or recurrent disease. Early‐life ...wheezing and asthma exacerbations are triggered by common respiratory viruses, mainly rhinoviruses (RV), and to a lesser extent, respiratory syncytial virus, parainfluenza, human metapneumovirus, coronaviruses, adenoviruses, influenza, and bocavirus. The excess presence of bacteria, several of which are part of the microbiome, has also been identified in association with wheezing and acute asthma exacerbations, including haemophilus influenza, streptococcus pneumoniae, moraxella catarrhalis, mycoplasma pneumoniae, and chlamydophila pneumonia. While it is not clear when asthma starts, its characteristics develop over time. Airway remodeling already appears between the ages of 1 and 3 years of age even prior to the presence of atopic inflammation or an asthma diagnosis. The role of genetic defect or variations hampering the airway epithelium in response to environmental stimuli and severe disease morbidity are now considered as major determinants for early structural changes. Repeated viral infections can induce and perpetuate airway hyperresponsiveness. Allergic sensitization, that often precedes infection‐induced wheezing, shifts inflammation toward type‐2, while common respiratory infections themselves promote type‐2 inflammation. Nevertheless, most children who wheeze with viral infections during infancy and during preschool years do not develop persistent asthma. Multiple factors, including illness severity, viral etiology, allergic sensitization, and the exposome, are associated with disease persistence. Here, we summarize current knowledge and developments in infection epidemiology of asthma in children, describing the known impact of each individual agent and mechanisms of transition from recurrent wheeze to asthma.
The clinical benefit of newer antihistamines (AHs) versus other active treatments has not been assessed in pediatric patients with allergic rhinitis.
A systematic literature search was performed in ...MEDLINE, SCOPUS, and the Cochrane Central Register of Controlled Trials from inception through August 2020. Randomized controlled trials (RCTs) comparing newer with older AHs, corticosteroids, or montelukast were included. The Cochrane Risk of Bias Tool was used for quality assessment.
Out of 10,656 citations, 16 RCTs (N = 1653) with a duration from 10 days to 3 months were included. When compared with older-generation AHs, the administration of newer AHs did not confer significant benefit and appeared less effective compared with intranasal corticosteroids. However, newer AHs were more potent in achieving symptom control compared with montelukast. Data regarding quality of life were generally missing. The incidence of adverse events was low in all treatment groups. The included RCTs were characterized by moderate risk of bias.
Newer AHs are effective in symptom control and well tolerated in the pediatric population. However, inadequate reporting, variation in outcome measures, and a paucity of sufficient randomized comparisons precluded us from quantifying the relative efficacy of newer AHs compared with other treatment options.
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