Abstract
Comparison of COVID-19 trends in space and over time is essential to monitor the pandemic and to indirectly evaluate non-pharmacological policies aimed at reducing the burden of disease. ...Given the specific age- and sex- distribution of COVID-19 mortality, the underlying sex- and age-distribution of populations need to be accounted for. The aim of this paper is to present a method for monitoring trends of COVID-19 using adjusted mortality trend ratios (AMTRs). Age- and sex-mortality distribution of a reference European population (N = 14,086) was used to calculate age- and sex-specific mortality rates. These were applied to each country to calculate the expected deaths. Adjusted Mortality Trend Ratios (AMTRs) with 95% confidence intervals (C.I.) were calculated for selected European countries on a daily basis from 17th March 2020 to 29th April 2021 by dividing observed cumulative mortality, by expected mortality, times the crude mortality of the reference population. These estimated the sex- and age-adjusted mortality for COVID-19 per million population in each country. United Kingdom experienced the highest number of COVID-19 related death in Europe. Crude mortality rates were highest Hungary, Czech Republic, and Luxembourg. Accounting for the age-and sex-distribution of the underlying populations with AMTRs for each European country, four different patterns were identified: countries which experienced a two-wave pandemic, countries with almost undetectable first wave, but with either a fast or a slow increase of mortality during the second wave; countries with consistently low rates throughout the period. AMTRs were highest in Eastern European countries (Hungary, Czech Republic, Slovakia, and Poland). Our methods allow a fair comparison of mortality in space and over time. These might be of use to indirectly estimating the efficacy of non-pharmacological health policies. The authors urge the World Health Organisation, given the absence of age and sex-specific mortality data for direct standardisation, to adopt this method to estimate the comparative mortality from COVID-19 pandemic worldwide.
Despite a substantial consistency in recommendations for the management of children with acute gastroenteritis (AGE), a high variability in clinical practice and a high rate of inappropriate medical ...interventions persist in both developing and developed countries.The aim of this study was to develop a set of clinical recommendations for the management of nonseverely malnourished children with AGE to be applied worldwide.
The Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) Working Group (WG) selected care protocols on the management of acute diarrhea in infants and children aged between 1 month and 18 years. The WG used a 3-step approach consisting of: systematic review and comparison of published guidelines, agreement on draft recommendations using Delphi methodology, and external peer-review and validation of recommendations.
A core of recommendations including definition, diagnosis, nutritional management, and active treatment of AGE was developed with an overall agreement of 91% (range 80%-96%). A total of 28 world experts in pediatric gastroenterology and emergency medicine successively validated the set of 23 recommendations with an agreement of 87% (range 83%-95%). Recommendations on the use of antidiarrheal drugs and antiemetics received the lowest level of agreement and need to be tailored at local level. Oral rehydration and probiotics were the only treatments recommended.
Universal recommendations to assist health care practitioners in managing children with AGE may improve practitioners' compliance with guidelines, reduce inappropriate interventions, and significantly impact clinical outcome and health care-associated costs.
Background
The efficacy of risk model scores to predict venous thromboembolism (VTE) in ambulatory cancer patients is under investigation, aiming to stratify on an individual risk basis the subset of ...the cancer population that could mostly benefit from primary thromboprophylaxis.
Materials and Methods
We prospectively assessed 843 patients with active cancers, collecting clinical and laboratory data. We screened all the patients with a duplex ultrasound (B‐mode imaging and Doppler waveform analysis) of the upper and lower limbs to evaluate the right incidence of VTE (both asymptomatic and symptomatic). The efficacy of the existing Khorana risk model in preventing VTE was also explored in our population. Several risk factors associated with VTE were analyzed, leading to the construction of a risk model. The Fine and Gray model was used to account for death as a competing risk in the derivation of the new model.
Results
The risk factors significantly associated with VTE at univariate analysis and further confirmed in the multivariate analysis, after bootstrap validation, were the presence of metastatic disease, the compression of vascular/lymphatic structures by tumor, a history of previous VTE, and a Khorana score >2. Time‐dependent receiving operating characteristic (ROC) curve analysis showed a significant improvement in the area under the curve of the new score over the Khorana model at 3 months (71.9% vs. 57.9%, p = .001), 6 months (75.4% vs. 58.6%, p < .001), and 12 months (69.8% vs. 58.3%, p = .014).
Conclusion
ONKOTEV score steps into history of cancer‐related‐VTE as a promising tool to drive the decision about primary prophylaxis in cancer outpatients. The validation represents the goal of the prospective ONKOTEV‐2 study, endorsed and approved by the European Organization for Research and Treatment of Cancer Young Investigators Program.
Implications for Practice
Preventing venous thromboembolism in cancer outpatients with a risk model score will drive physicians' decision of starting thromboprophylaxis in high‐risk patients.
Stratification of risk through predictive models is a strategic method for reducing the burden of venous thromboembolism in cancer patients. The objective of this study was to derivate a novel predictive scoring tool for measuring the risk of the individual patient.
Autosomal dominant polycystic kidney disease (ADPKD) accounts for 8-10% of end-stage chronic kidney disease (CKD) patients worldwide. In the last decade, the advanced knowledge in genetics and ...molecular pathobiology of ADPKD focused some aberrant molecular pathways involved in the pathogenesis of the disease leading to controlled clinical trials aimed to delay its progression with the use of mTOR inhibitors, somatostatin or tolvaptan. Preclinical studies suggests an effective role of metformin in ADPKD treatment by activating AMPK sensor. Clinical trials are currently recruiting participants to test the metformin use in ADPKD patients.
We retrospectively examined the records of our ADPKD patients, selecting 7 diabetic ADPKD patients under metformin treatment and 7 matched non-diabetic ADPKD controls, to test the effect of metformin on renal progression during a 3 year follow-up.
During the first year, the GFR decreased by 2.5% in Metformin Group and by 16% in Controls; thereafter, renal function remained stable in Metformin Group and further decreased in Controls, reaching a 50% difference after 3 years of observation. Accordingly, the overall crude loss of GFR, estimated by a linear mixed model, resulted slower in the Metformin than in Control Group (- 0.9; 95% C.I.: -2.7 to 0.9 vs - 5.0; 95% C.I.: -6.8 to - 3.2 mL/min/1.73 m2 per year, p = 0.002).
Our data are suggestive of a beneficial effect of metformin on progression of ADPKD. Large, randomized, prospective trials are needed to confirm this hypothesis.
Accommodative esotropia (AE) is a convergent deviation due to an excess of the convergence linked to the innervational stimulus for accommodation and it is usually associated to the presence of ...hyperopia. The development of hyperopia over time has been widely described but the lack of comparative analysis among accommodative esotropia subtypes, does not allow to verify the existence of different developmental patterns. In this study we aimed to describe the long term changes of refractive error in patients affected by accommodative esotropia as a function of the strabismus type: refractive (RAE), non-refractive (NRAE) and partially accommodative esotropia (PAE). The medical records of 66 patients (24 RAE, 22 PAE, 20 NRAE), who wore the full correction of their cycloplegic refraction error during the entire follow up period, were retrospectively reviewed. Mean outcome was the analysis of the variations, among groups, of refractive error over time; differences between mild (≤3.00D) and high (≥5.00D) hyperopia, effects of amblyopia and relationship with AC/A ratio were also investigated. All patients were followed up from approximately 4 years of age to 20, with mean follow up of 16.06±0.29 years. Our results described similar non-linear trend of refractive error development among groups. The initial increase of hyperopia (up to 7-8 years) was followed by a decreasing trend persisting up to adulthood (approximately 20 years of age). During this period, spherical equivalent decreased at a lower mean annual rate in patients affected by RAE (-0.07D) compared to other groups (NRAE -0.11D, p = 0.003 and PAE 0.13D, p = 0.002). In all groups, however, significant amount of hyperopia was found at last examination; indeed the observed difference in SE values from baseline to the end of follow up, was not significant (RAE: +0.27D, 95% C.I. -0.49 to +1.04D, p = 0.472; PAE: -0.69D, 95% C.I. -1.67 to +0.28D, p = 0.154; NRAE: -0.39D, 95% C.I. -1.11 to +0.34D, p = 0.278). AC/A ratio, amblyopia and amount of initial hyperopia appeared to have no significant role in longitudinal change of the refractive error. In conclusion, this study provides a complete overview, from childhood to adulthood, of refractive error development in different form of accommodative esotropia.
Background/Aims
Functional constipation (FC) is aa frequent functional gastrointestinal disorder, diagnosed according to the Rome criteria. In this study, we compared Rome III and Rome IV criteria ...for the diagnosis of FC, and determined the prevalence of FC according to these criteria.
Methods
Consecutive children between infancy and 17 years old were recruited for the study, excluding those with a known organic gastrointestinal disease. A prospective longitudinal design has beenused. For the diagnosis of FC, questionnaires on Pediatric Gastrointestinal Symptoms (QPGS) based on the Rome III and Rome IV criteria (QPGS-RIII and QPGS-RIV) were used. The agreement between these 2 questionnaires was measured by Cohen’s kappa coefficient.
Results
Two hundred fourteen children (mean age, 77.4 ± 59.5 months; 103 males) were screened. There was no statistically significant difference in the prevalence of FC evaluated using the QPGS-Rome IV vs the QPGS-Rome III in the overall sample (39/214 18.2% vs 37/214 17.3.0%; P = 0.831) as well as in any of the groups. The Cohen’s kappa test showed a good agreement between the 2 criteria (κ = 0.65; 95% CI, 0.51 to 0.78).
Conclusion
Our study demonstrates that the new Rome IV criteria have a good agreement with the Rome III criteria for the diagnosis of FC, without an increase in the number of potential diagnoses, despite the reduction in the duration of the symptoms. This conclusion is important in the management of childhood FC, since a late diagnosis negatively affects the prognosis.
(J Neurogastroenterol Motil 2019;25:123-128)
Background and Aims EndoCuff is a disposable device applied to standard colonoscopes to improve mucosal visualization. Randomized parallel trials have shown that EndoCuff increases the adenoma ...detection rate (ADR). The primary aim of this study was to compare the ADR between EndoCuff-assisted colonoscopies (EAC) and standard colonoscopies within a randomized back-to-back trial. Methods This was a single-center randomized crossover study (NCT02374515) involving adult patients undergoing screening, surveillance, or diagnostic colonoscopy. Participants received back-to-back standard colonoscopies and EACs in a random order, performed by the same endoscopist. All polyps were excised, but only those proven at histology to be adenomas were considered for analysis. Results From February 2015 to March 2016, a total of 288 patients were enrolled, and 274 were included in the per-protocol analysis. Compared with standard colonoscopies, EACs increased the ADR (29.6% vs 26.3%; P < .01) and the number of diagnosed adenomas (176 vs 129; P < .01), particularly in the left (73 vs 46; P < .01) and right sides of the colon (83 vs 63; P < .01). EAC increased the detection of adenomas <5 mm (129 vs 84; P < .01), but no difference was found with regard to larger lesions. In 7.3% of patients, findings of EndoCuff shortened the surveillance interval determined by standard colonoscopy findings. EndoCuff caused 7 mucosal erosions (2.5% of patients), requiring a mucosal adrenaline injection in 1 case. Conclusions The use of EndoCuff increases the number of identified adenomas, primarily small adenomas in the left and right sides of the colon. This increases the ADR and allows a better definition of the surveillance program. (Clinical trial registration number: NCT02374515 .)
Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose ...tolerance is not clear.
Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA.
Serum levels of IL-9, IL-13, and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines.
In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.
Widespread use of PSA as the standard tool for prostate cancer (PCa) diagnosis led to a high rate of overdiagnosis and overtreatment. In this study, we evaluated the performance of the prostate ...health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) for the prediction of positive biopsy and of high-grade PCa at radical prostatectomy (RP). To this end, we prospectively enrolled 196 biopsy-naïve patients who underwent mpMRI. A subgroup of 116 subjects with biopsy-proven PCa underwent surgery. We found that PHI significantly outperformed both PI-RADS score (difference in AUC: 0.14; p < 0.001) and PHI density (difference in AUC: 0.08; p = 0.002) in the ability to predict positive biopsy with a cut-off value of 42.7 as the best threshold. Conversely, comparing the performance in the identification of clinically significant prostate cancer (csPCa) at RP, we found that PHI ≥ 61.68 and PI-RADS score ≥ 4 were able to identify csPCa (Gleason score ≥ 7 (3 + 4)) both alone and added to a base model including age, PSA, fPSA-to-tPSA ratio and prostate volume. In conclusion, PHI had a better ability than PI-RADS score to predict positive biopsy, whereas it had a comparable performance in the identification of pathological csPCa.
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