A Delphi process to optimize quality and performance of drug evaluation in neonates

Background Neonatal trials remain difficult to conduct for several reasons: in particular the need for study sites to have an existing infrastructure in place, with trained investigators and validated quality procedures to ensure good clinical, laboratory practices and a respect for high ethical standards. The objective of this work was to identify the major criteria considered necessary for selecting neonatal intensive care units that are able to perform drug evaluations competently. Methodology and Main Findings This Delphi process was conducted with an international multidisciplinary panel of 25 experts from 13 countries, selected to be part of two committees (a scientific committee and an expert committee), in order to validate criteria required to perform drug evaluation in neonates. Eighty six items were initially selected and classified under 7 headings: “NICUs description - Level of care” (21), “Ability to perform drug trials: NICU organization and processes (15), “Research Experience” (12), “Scientific competencies and area of expertise” (8), “Quality Management” (16), “Training and educational capacity” (8) and “Public involvement” (6). Sixty-one items were retained and headings were rearranged after the first round, 34 were selected after the second round. A third round was required to validate 13 additional items. The final set includes 47 items divided under 5 headings. Conclusion A set of 47 relevant criteria will help to NICUs that want to implement, conduct or participate in drug trials within a neonatal network identify important issues to be aware of. Summary Points 1) Neonatal trials remain difficult to conduct for several reasons: in particular the need for study sites to have an existing infrastructure in place, with trained investigators and validated quality procedures to ensure good clinical, laboratory practices and a respect for high ethical standards. 2) The present Delphi study was conducted with an international multidisciplinary panel of 25 experts from 13 countries and aims to identify the major criteria considered necessary for selecting neonatal intensive care units (NICUs) that are able to perform drug evaluations competently. 3) Of the 86 items initially selected and classified under 7 headings - “NICUs description - Level of care” (21), “Ability to perform drug trials: NICU organization and processes (15), “Research Experience” (12), “Scientific competencies and area of expertise” (8), “Quality Management” (16), “Training and educational capacity” (8) and “Public involvement” (6) - 47 items were selected following a three rounds Delphi process. 4) The present consensus will help NICUs to implement, conduct or participate in drug trials within a neonatal network

Informed consent and new legislation

El presente artículo pretende recopilar conceptos sobre el Consentimiento Informado para actualizar sus significados en el ámbito de la Odontología Legal y su relación con la práctica profesional. Se reconoce al consentimiento informado como un documento de enorme relevancia para el paciente. La sociedad actual considera como eje central a la persona humana y la satisfacción de sus derechos, por ello en la normativa vigente es necesario modificar y modernizar la legislación civil y comercial dando respuesta a transformaciones culturales.This article aims to compile concepts about Informed Consent to update its meanings in the field of Legal Dentistry and its relationship with professional practice. Informed consent is recognized as a document of great relevance to the patient. The current society considers the human person as a central axis and the satisfaction of their rights, so in current regulations it is necessary to modify and modernize civil and commercial legislation in response to cultural transformations.Fil: González, Silvia Inés. Universidad Nacional de Cuyo. Facultad de OdontologíaFil: Von Katona, Alejandro. Universidad Nacional de Cuyo. Facultad de OdontologíaFil: Valls, Elizabeth. Universidad Nacional de Cuyo. Facultad de Odontologí

Characterization of digestive involvement in patients with chronic T. cruzi infection in Barcelona, Spain

Background: Digestive damage due to Chagas disease (CD) occurs in 15-20% of patients diagnosed as a result of peristaltic dysfunction in some endemic areas. The symptoms of chronic digestive CD are non-specific, and there are numerous confounders. Diagnosis of CD may easily be missed if symptoms are not evaluated by a well trained physician. Regular tests, as barium contrast examinations, probably lack the necessary sensitivity to detect early digestive damage. Methods: 71 individuals with T. cruzi infection (G1) and 18 without (G2) coming from Latin American countries were analyzed. They were asked for clinical and epidemiological data, changes in dietary habits, and history targeting digestive and cardiac CD symptoms. Serological tests for T. cruzi, barium swallow, barium enema, an urea breath test, and esophageal manometry were requested for all patients. Principal findings: G1 and G2 patients did not show differences in lifestyle and past history. Fifteen (21.1%) of G1 had digestive involvement. Following Rezende criteria, esophagopathy was observed in 8 patients in G1 (11.3%) and in none of those in G2. Manometry disorders were recorded in 34 G1 patients and in six in G2. Isolated hypotensive lower esophageal sphincter (LES) was found in sixteen G1 patients (23.9%) and four G2 patients (28.8%). Achalasia was observed in two G1 patients. Among G1 patients, ineffective esophageal motility was seen in six (five with symptoms), diffuse esophageal spasm in two (one with dysphagia and regurgitation), and nutcracker esophagus in three (all with symptoms). There were six patients with hypertonic upper esophageal sphincter (UES) among G1. Following Ximenes criteria, megacolon was found in ten G1 patients (13.9%), and in none of the G2 patients. Conclusions: The prevalence of digestive chronic CD in our series was 21.1%. Dysphagia is a non-pathognomonic symptom of CD, but a good marker of early esophageal involvement. Manometry could be a useful diagnostic test in selected cases, mainly in patients with T. cruzi infection and dysphagia in whose situation barium swallow does not evidence alterations. Constipation is a common but non-specific symptom that can be easily managed. Testing for CD is mandatory in a patient from Latin America with constipation or dysphagia, and if diagnosis is confirmed, megacolon and esophageal involvement should be investigated

Assessment of the level III of Inoue by preoperative endoscopic ultrasound and elastography: a novel approach to predict a periarterial divestment technique in borderline resectable (BR) or locally advanced (LA) pancreatic adenocarcinoma—How I do it

Pancreatic cancer; Periarterial divestment; Triangle operationCáncer de páncreas; Desinversión periarterial; Operación triangularCàncer de pàncrees; Desinversió periarterial; Operació triangularBackground Periarterial divestment is a surgical technique to approach borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) with arterial involvement. There are no reports in the literature regarding the role of endoscopic ultrasound and elastography (EUS-EG) in exploring the integrity of Inoue’s level III and its correlation with the periarterial divestment technique feasibility. Our research is aimed at exploring the role of EUS-EG in this scenario. Methods We describe our approach to Inoue’s level II by EUS-EG in patients with BR and LA pancreatic cancer patients after neoadjuvant chemotherapy. Results Between June 2019 and December 2020, four patients out of 25 were eligible to perform a preoperative EUS-EG. In all cases, Inoue’s level III integrity was corroborated by EUS-EG and confirmed posteriorly in the surgical scenario where a periarterial divestment technique was feasible. Vein resections were necessary in all cases, with no need for arterial resection. An R0 (> 1 mm) margin was achieved in all patients, and the histopathological assessment showed the presence of neurovascular tissue at the peripheral arterial margin. Conclusion Preoperatively, EUS-EG is a novel approach to explore the integrity of Inoue’s level III and could be helpful to preclude a periarterial divestment technique in borderline resectable or locally advanced pancreatic adenocarcinoma with arterial involvement.Open Access Funding provided by Universitat Autonoma de Barcelona

The role of clinically relevant intra-abdominal collections after pancreaticoduodenectomy

Pancreatectomy complications; Pancreatic fistula; Postoperative collectionsComplicaciones de pancreatectomía; Fístula pancreática; Colecciones postoperatoriasComplicacions de pancreatectomia; Fístula pancreàtica; Col·leccions postoperatòriesBackground There is controversial evidence regarding the impact of clinically relevant postoperative intra-abdominal collections (CR-IC) on the clinical course after pancreaticoduodenectomy. C-reactive Protein (CRP) has been validated as a predictor of postoperative pancreatic fistula (POPF). Still, its role in predicting CR-IC has not been studied. Methods A retrospective analysis was conducted on patients who underwent PD at a tertiary hospital between October 2012 and October 2017. The incidence of CR-IC, clinically relevant POPF and other complications, as well as mortality and length of hospitalisation, was retrieved. The impact of CR-IR on mortality and major complications was analysed. The serum CRP levels were retrieved on the third and fifth postoperative days (POD3 and POD5), followed by an analysis of sensitivity, specificity, and area under the curve to predict CR-IC using CRP. Results One hundred forty patients were enrolled following inclusion and exclusion criteria. The mean age was 66.5 years (15–83). The incidence of CR-IC was 33.7% (47), and CR-POPF was 24.3%. Pancreatic duct diameter ≤ 4 mm was identified as a risk factor related to CR-IC occurrence. The group of patients who developed CR-IC after PD exhibited a higher rate of complications Clavien-Dindo ≥ III compared to patients without CR-IC (40.4% vs 7.5%, p  III: OR = 10.6 (95% CI: 3.90–28.7). No differences in mortality were reported between the CR-IC group and non-CR-IC group. CRP at postoperative day 3 (POD3) > 17.55 mg/dl and CRP at postoperative day 5 (POD5) > 13.46 mg/dl were predictors of CR-IC (AUC: 0.731 and AUC:0.821, respectively). Conclusions CR-IC has a significant impact after pancreaticoduodenectomy and is associated with a higher incidence of Clavien-Dindo ≥ III complications. Additionally, CRP levels at POD3 and POD5 play a role in predicting CR-IC. Prospective studies are essential to explore strategies for mitigating the occurrence of CR-IC after PD.Open Access Funding provided by Universitat Autonoma de Barcelona

Impact of comorbidities on hospital mortality in patients with acute pancreatitis: a population-based study of 110,021 patients

Acute pancreatitis; Comorbidity; Hospital mortalityPancreatitis aguda; Comorbilidad; Mortalidad hospitalariaPancreatitis aguda; Comorbilitat; Mortalitat hospitalàriaBackground The impact of pre-existing comorbidities on acute pancreatitis (AP) mortality is not clearly defined. Our study aims to determine the trend in AP hospital mortality and the role of comorbidities as a predictor of hospital mortality. Methods We analyzed patients aged ≥ 18 years hospitalized with AP diagnosis between 2016 and 2019. The data have been extracted from the Spanish National Hospital Discharge Database of the Spanish Ministry of Health. We performed a univariate and multivariable analysis of the association of age, sex, and comorbidities with hospital mortality in patients with AP. The role of the Charlson and Elixhauser comorbidity indices as predictors of mortality was evaluated. Results A total of 110,021 patients diagnosed with AP were hospitalized during the analyzed period. Hospital mortality was 3.8%, with a progressive decrease observed in the years evaluated. In multivariable analysis, age ≥ 65 years (OR: 4.11, p  1.5 (OR: 2.03, p  1.5 (OR: 2.71, p < 0.001) comorbidity indices were also independently associated with mortality, and ROC curve analysis showed that they are useful for predicting hospital mortality. Conclusions Advanced age, heart disease, renal disease, moderate-severe liver disease, peripheral vascular disease, and cerebrovascular disease before admission were independently associated with hospital mortality. The Charlson and Elixhauser comorbidity indices are useful for predicting hospital mortality in AP patients. Peer Review reports Background Acute pancreatitis (AP) is a prevalent acute inflammatory disease that affects the pancreas, with an increased incidence in recent years [1, 2]. Most cases are mild with a self-limited course [3]. However, patients with severe acute pancreatitis have a high mortality rate (20–50%) [4,5,6]. For this reason, many efforts have been made to find predictors of severity and mortality in patients with AP [7,8,9,10,11] to identify patients who need admission to an intensive care unit or specific treatment. In clinical practice, systems such as the Ranson score, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, the Computed Tomography Severity Index (CTSI), the Bedside Index for Severity in Acute Pancreatitis (BISAP), and various biochemical markers are used to predict severe AP and mortality [3, 12,13,14,15,16]. However, hospital mortality in AP could also be related to intrinsic patient characteristics, such as individual comorbidities. Most classic scores do not consider comorbidities before admission, except for APACHE II, but are restricted to severe chronic diseases. According to some previous studies, patients with certain comorbidities, such as obesity [17], hypertriglyceridemia [18], chronic renal failure [19], diabetes [20, 21], and systemic lupus erythematosus [22], are associated with a higher risk of AP severity and mortality. However, few studies currently evaluate the impact of comorbidities on AP severity and mortality. Our study aimed to determine the relevance of comorbidities and their indexes (Charlson and Elixhauser) as predictors of hospital mortality in patients with AP

The role of high serum triglyceride levels on pancreatic necrosis development and related complications

Acute pancreatitis; Pancreatic necrosis; TriglyceridePancreatitis aguda; Necrosi pancreàtica; TriglicèridsPancreatitis aguda; Necrosis pancreática; TriglicéridosBackground The relevance of elevated serum triglyceride (TG) levels in the early stages of acute pancreatitis (AP) not induced by hypertriglyceridemia (HTG) remains unclear. Our study aims to determine the role of elevated serum TG levels at admission in developing pancreatic necrosis. Methods We analyzed the clinical data collected prospectively from patients with AP. According to TG levels measured in the first 24 h after admission, we stratified patients into four groups: Normal TG (< 150 mg/dL), Borderline-high TG (150–199 mg/dL), High TG (200–499 mg/dL) and Very high TG (≥ 500 mg/dL). We analyzed the association of TG levels and other risk factors with the development of pancreatic necrosis. Results A total of 211 patients were included. In the Normal TG group: 122, in Borderline-high TG group: 38, in High TG group: 44, and in Very high TG group: 7. Pancreatic necrosis developed in 29.5% of the patients in the Normal TG group, 26.3% in the Borderline-high TG group, 52.3% in the High TG group, and 85.7% in the Very high TG group. The trend analysis observed a significant association between higher TG levels and pancreatic necrosis (p = 0.001). A multivariable analysis using logistic regression showed that elevated TG levels ≥ 200 mg/dL (High TG and Very high TG groups) were independently associated with pancreatic necrosis (OR: 3.27, 95% CI − 6.27, p < 0.001). Conclusions An elevated TG level at admission ≥ 200 mg/dl is independently associated with the development of pancreatic necrosis. The incidence of pancreatic necrosis increases proportionally with the severity of HTG

Elevated Serum Triglyceride Levels in Acute Pancreatitis: A Parameter to be Measured and Considered Early

Triglicéridos séricos; Pancreatitis agudaTriglicèrids sèrics; Pancreatitis agudaAcute pancreatitis; Serum triglycerideBackground The value of serum triglycerides (TGs) related to complications and the severity of acute pancreatitis (AP) has not been clearly defined. Our study aimed to analyze the association of elevated levels of TG with complications and the severity of AP. Methods The demographic and clinical data of patients with AP were prospectively analyzed. TG levels were measured in the first 24 h of admission. Patients were divided into two groups: one with TG values of<200 mg/dL and another with TG≥200 mg/dL. Data on the outcomes of AP were collected. Results From January 2016 to December 2019, 247 cases were included: 200 with TG<200 mg/dL and 47 with TG≥200 mg/dL. Triglyceride levels≥200 mg/dL were associated with respiratory failure (21.3 vs. 10%, p=0.033), renal failure (23.4 vs. 12%, p=0.044), cardiovascular failure (19.1 vs. 7.5%, p=0.025), organ failure (34 vs. 18.5%, p=0.02), persistent organ failure (27.7 vs. 9.5%, p=0.001), multiple organ failure (19.1 vs. 8%, p=0.031), moderately severe and severe AP (68.1 vs. 40.5%, p=0.001), pancreatic necrosis (63.8 vs. 34%, p<0.001), and admission to the intensive care unit (27.7 vs. 9.5%, p=0.003). In the multivariable analysis, a TG level of≥200 mg/dL was independently associated with respiratory, renal, and cardiovascular failure, organ failure, persistent organ failure, multiple organ failure, pancreatic necrosis, severe pancreatitis, and admission to the intensive care unit (p<0.05). Conclusions In our cohort, TG≥200 mg/dL was related to local and systemic complications. Early determinations of TG levels in AP could help identify patients at risk of complications.Open Access Funding provided by Universitat Autonoma de Barcelona