Quality Standards in Upper Gastrointestinal Endoscopy: Can Deep Sedation Influence It?

Introduction: According to the guideline published by ESGE/UEG, a high-quality esophagogastroduodenoscopy (EGD) implies the application of some criteria that enable better healthcare outcomes. Although intra-procedural performance measures are dependent on patient factors, there is no reference to sedation practices in the guideline mentioned above. Objective: This study aimed to evaluate whether deep sedation influences EGD performance measures established by ESGE/UEG. Methods: This was a cross-sectional study, with a prospective enrollment, that considered for inclusion consecutive patients referred for EGD. Two questionnaires were used to assess performance measures and patient satisfaction after EGD. Results: Sedation had a statistically significant impact on most quality indicators, including complete examination (77.2% without sedation vs. 97.8% with sedation), inspection time (6.17 ± 3.45 vs. 8.39 ± 2.67 min), photodocumentation (78% vs. 97.8%), biopsies (39.3% vs. 60.7%), and patient satisfaction (5.42 ± 2.93 vs. 9.1 ± 1.19). The main reason for an incomplete procedure was patient intolerance (82.6%). Discussion: Deep sedation of patients submitted to EGD proved to be a determinant in the applicability of the ESGE/UEG quality indicators. Patient intolerance was eliminated in the group with sedation, enhancing procedure completeness, adequate pathology identification, management, and consequently, the effectiveness of the exam. Conclusion: Sedation administration should be considered in patients undergoing EGD since it ensures a high-quality procedure.

Introdução: Uma endoscopia digestiva alta (EDA) de qualidade proporciona melhores resultados em termos de saúde e implica a aplicação dos critérios descritos pelas recomendações da ESGE/UEG. Embora os critérios perprocedimento sejam dependentes da colaboração e tolerância do doente, não está explicito o papel da anestesia. Objetivos: Este estudo pretende avaliar se o recurso a anestesia influencia o cumprimento dos critérios de qualidade para a EDA publicados pela ESGE/UEG. Materiais e métodos: Estudo transversal, com recrutamento prospetivo, que incluiu pacientes consecutivamente encaminhados para realização de EDA. Foram utilizados 2 questionários para avaliar medidas de desempenho e satisfação dos pacientes após realização de EDA. Resultados: A anestesia teve um impacto estatisticamente significativo na maioria dos indicadores de qualidade: exame completo (77,2% sem anestesia vs. 97,8% com anestesia); tempo de inspeção (6,17 ± 3,45 vs. 8,39 ± 2,67 minutos); fotodocumentação (78% vs. 97,8%); biópsias (39,3% vs. 60,7%); satisfação do paciente (5,42 ± 2,93 vs. 9,1 ± 1,19). O principal motivo para um procedimento incompleto foi a intolerância do paciente (82,6%). Discussão: A sedação profunda dos doentes submetidos a EDA provou ser determinante na aplicabilidade dos critérios de qualidade da ESGE/UEG. Eliminando por completo a intolerância por parte do doente, proporcionou a realização de exames completos, com correta identificação e gestão de patologias, potenciando assim a efetividade do exame. Conclusão: A administração de anestesia deve ser ponderada, sempre que possível, nos doentes submetidos a EDA, visto que permite garantir a alta qualidade do procedimento.

Further Studies on the Highly Active Des-C-Ring and Aromatic-D-Ring Analogues of 1α,25-Dihydroxyvitamin D3 (Calcitriol): Refinement of the Side Chain.

Current efforts in the vitamin D field are directed toward the development of highly antiproliferative yet noncalcemic analogues of the natural hormone 1α,25-dihydroxyvitamin D3 (1,25D3). We have recently reported the design, synthesis, biological evaluation, and crystal structures of a series of novel analogues that both lack the steroidal C-ring and have an m-phenylene ring replacing the steroidal cyclopentane D-ring. We have now investigated the potentiating effects of incorporating selected modifications (hexafluorination and/or an internal triple bond) within the steroidal side chain in our series. An alternative synthetic strategy (Wittig-Horner approach instead of our previously used Pd-catalyzed tandem cyclization/cross-coupling) for the construction of the vitamin D triene system was found convenient for the target compounds 2, 3a, 3b, and 3c of this report. These modifications enhance vitamin D nuclear receptor (VDR) interactions and consequently VDR-associated biological properties compared to parental PG-136 compound while maintaining normal calcium levels.

Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Shift in the Microbial Pattern? A Retrospective Analysis.

Introduction: Over the last decade, a shift in the spontaneous bacterial peritonitis (SBP) microbial pattern toward an increasing incidence of gram-positive and multidrug-resistant (MDR) bacteria has been reported. Systematic surveillance of the local microbiological scenario and antibiotic resistance is crucial to SBP treatment success. The main objective of this study was to evaluate the microbiological profile and bacterial resistance of SBP pathogens in a Portuguese cohort to allow selection of the most appropriate empirical antibiotics. Methods: This is a single-center retrospective study including 63 adult cirrhotic patients with culture-positive SBP. Patients were identified using a hospital general diagnostic database and searching for all SBP events (neutrophil count in ascitic fluid ≥250/mm3) from January 1, 2012, to December 31, 2017. Patients were excluded if they had culture-negative SBP, secondary peritonitis, peritoneal dialysis, a liver transplant, or immunodeficiency. The site of SBP acquisition was classified as nosocomial if it was diagnosed 48 h or longer after hospitalization or as nonnosocomial if it was diagnosed within the first 48 h. MDR bacteria were those with an acquired resistance to at least 1 agent in 3 or more antimicrobial categories. All statistical analyses were carried out using IBM SPSS Statistics software version 22 (IBM, New York, USA). Results: The study cohort comprised 53 (84.1%) men. The mean age of the patients was 60.6 ± 11.2 years. Alcohol was the most common etiology (88.9%) and most patients had advanced liver cirrhosis (87.1%, Child C). Gram-negative bacteria were slightly more frequent than gram-positive bacteria (56.9 vs. 43.1%). Escherichia coli was the most common pathogen (33.8%). Nineteen (31.7%) bacteria were classified as MDR. Resistance to third-generation cephalosporins, quinolones, piperacillin-tazobactam, and carbapenems was found in 31.7, 35, 26.7, and 18.3% of the cases, respectively. The rates of gram-positive bacteria were similar between nosocomial and nonnosocomial episodes (45 vs. 42.2%; p = 0.835). MDR bacteria were more common in the nosocomial group (50 vs. 23.8%; p = 0.046). Resistance to third-generation cephalosporins (50 vs. 23.8%; p = 0.046), piperacillin-tazobactam (44.4 vs. 19.1%; p = 0.041), and carbapenems (33.3 vs. 11.9%; p = 0.049) occurred more frequently in nosocomial episodes. Resistance to first-line antibiotic occurred in 29.3% of the patients, being more common in the nosocomial group (44.4 vs. 22.5%; p = 0.089). Conclusion: Although gram-negative bacteria remain the most common causative microorganisms, our results emphasize the shift in SBP microbiological etiology, as almost half of the isolated microorganisms were gram positive. The emergence of bacteria resistant to traditionally recommended empirical antibiotics underlines the importance of basing this choice on local flora and antibiotic susceptibility data, allowing a more rational and successful use of antibiotics.

Introdução: Na última década assistiu-se a uma mudança no padrão microbiológico da peritonite bacteriana espontânea (PBE), com aumento da incidência de bactérias gram-positivas e multirresistentes. Uma vigilância sistemática do cenário microbiológico e da resistência antibiótica é crucial para o sucesso do tratamento da PBE. O principal objetivo deste estudo foi avaliar o perfil microbiológico e os padrões de resistência antibiótica dos agentes bacterianos responsáveis pelos casos de PBE numa coorte portuguesa de doentes cirróticos, de modo a permitir uma seleção mais apropriada da antibioterapia empírica. Métodos: Estudo retrospetivo unicêntrico, que incluiu 63 doentes adultos cirróticos com PBE culturapositiva. A identificação dos doentes foi efetuada a partir da base de dados eletrónica do centro hospitalar, pesquisando todos os internamentos por PBE (contagem de neutrófilos no líquido ascítico ≥250/mm3) entre 1 janeiro de 2012 e 31 de dezembro de 2017. Foram aplicados como critérios de exclusão: cultura de líquido ascítico negativa, peritonite secundária, diálise peritoneal, transplante hepático ou imunodeficiência. O local de aquisição da PBE foi classificado como nosocomial se diagnóstico após as primeiras 48 horas de hospitalização, e não-nosocomial se diagnóstico nas primeiras 48 horas. Multirresistência foi definida como resistência adquirida a pelo menos um agente em três ou mais categorias antimicrobianas. A análise estatística foi efetuada com recurso ao software IBM SPSS Statistics versão 22 (IBM, New York, USA). Resultados: A coorte incluiu 53 (84.1%) doentes cirróticos do género masculino. A idade média dos doentes foi de 60.6 ± 11.2 anos. O álcool constituiu a etiologia mais comum (88.9%) e a maioria dos doentes apresentava uma cirrose em estadio avançado (87.1%, Child-C). As bactérias gram-negativas revelaram-se ligeiramente mais frequentes que as gram-positivas (56.9 vs. 43.1%). Escherichia coli foi o microrganismo mais frequente (33.8%). Dezanove (31.7%) das bactérias isoladas foram classificadas como multirresistentes. As resistências às cefalosporinas de terceira-geração, às quinolonas, à piperacilina-tazobactam e aos carbapenemes foram de 31.7, 35, 26.7 e 18.3%, respetivamente. A taxa de bactérias gram-positivas foi similar entre PBE nosocomial e não-nosocomial (45 vs. 42.2%; p = 0.835). As bactérias multirresistentes foram mais frequentes no grupo nosocomial (50 vs. 23.8%; p = 0.046). A resistência às cefalosporinas de terceira-geração (50 vs. 23.8%; p = 0.046), à piperacilina-tazobactam (44.4 vs. 19.1%; p = 0.041) e aos carbapenemes (33.3 vs. 11.9%; p = 0.049) foi significativamente superior nas infeções nosocomiais. A resistência à antibioterapia empírica de primeira linha ocorreu em 29.3% dos doentes, sendo mais frequente no grupo nosocomial (44.4 vs. 22.5%; p = 0.089). Conclusão: Apesar de as bactérias gram-negativas constituírem, nesta coorte, a maioria dos microrganismos responsáveis pela PBE, os nossos resultados enfatizam a mudança na etiologia microbiológica da PBE, na medida em que, quase metade dos microrganismos isolados foram gram-positivos. A emergência de bactérias resistentes aos antibióticos empíricos tradicionalmente recomendados sublinha a importância de basear esta escolha nos dados locais sobre flora bacteriana e susceptibilidade antibiótica, permitindo uma escolha mais racional e um uso bem-sucedido dos antibióticos.

Nasopharyngeal Panbio COVID-19 Antigen Performed at Point-of-Care Has a High Sensitivity in Symptomatic and Asymptomatic Patients With Higher Risk for Transmission and Older Age.

BACKGROUND: Performance of point-of-care tests in different clinical scenarios and on different samples remains undetermined. We comprehensively evaluated the performance of the nasopharyngeal Panbio COVID-19 Ag Rapid Test Device. METHODS: This is a prospective study that includes consecutive patients attending 3 primary care centers (PCCs) and an emergency department. The antigen test was performed at point-of-care in nasopharyngeal and nasal swabs and in saliva. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated with the reverse-transcription polymerase chain reaction (RT-PCR) assay as reference standard. RESULTS: Of 913 patients included, 296 (32.3%) were asymptomatic and 690 (75.6%) came from the PCC. Nasopharyngeal swabs were collected from 913 patients, nasal swabs were collected from 659 patients, and saliva was collected from 611 patients. The RT-PCR was positive in 196 (21.5%) nasopharyngeal samples (NPS). Overall, PPA (95% CI) in NPS was 60.5% (53.3-67.4), and it was lower in nasal swabs (44.7%) and saliva (23.1%). Test performance in NPS was largely dependent on the cycle threshold (Ct) in RT-PCR, with PPA of 94% for Ct ≤25 and 80% for Ct <30. In symptomatic patients, the PPA was 95% for Ct ≤25, 85% for Ct <30, and 89% for the symptom triad of fever, cough, and malaise. Performance was also dependent on age, with a PPA of 100% in symptomatic patients >50 years with Ct <25. In asymptomatic patients, the PPA was 86% for Ct <25. In all cases, NPA was 100%. CONCLUSIONS: The nasopharyngeal Panbio COVID-19 Ag test performed at point-of-care has a good sensitivity in symptomatic patients with Ct <30 and older age. The test was useful to identify asymptomatic patients with lower Ct values.

Performance of Saliva Specimens for the Molecular Detection of SARS-CoV-2 in the Community Setting: Does Sample Collection Method Matter?

Data on the performance of saliva specimens for diagnosing coronavirus disease 2019 (COVID-19) in ambulatory patients are scarce and inconsistent. We assessed saliva-based specimens for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase PCR (RT-PCR) in the community setting and compared three different collection methods. This prospective study was conducted in three primary care centers. RT-PCR was performed on paired nasopharyngeal swabs (NPS) and saliva samples collected from outpatients with a broad clinical spectrum of illness. To assess differences in collection methods, saliva specimens were obtained in a different way in each of the participating centers: supervised collection (SVC), oropharyngeal washing (OPW), and self-collection (SC). Pairs of NPS and saliva samples from 577 patients (median age, 39 years; 44% men; 42% asymptomatic) were collected and tested, and 120 (20.8%) gave positive results. The overall agreement with NPS results and kappa coefficients (κ) for saliva samples obtained by SVC, OPW, and SC were 95% (κ = 0.85), 93.4% (κ = 0.76), and 93.3% (κ = 0.76), respectively. The sensitivities (95% confidence intervals [95% CI]) of the saliva specimens ranged from 86% (72.6% to 93.7%) for SVC to 66.7% (50.4% to 80%) for SC samples. Sensitivity was higher for samples with lower cycle threshold (CT ) values. The best RT-PCR performance was observed for SVC, with sensitivities (95% CI) of 100% (85.9% to 100%) in symptomatic individuals and 88.9% (50.7% to 99.4%) in asymptomatic individuals at CT values of ≤30. We conclude that saliva is an acceptable specimen for the detection of SARS-CoV-2 in the community setting. Specimens collected under supervision perform comparably to NPS and can effectively identify individuals at higher risk of transmission under real-life conditions.

Twelve-day quintuple regime containing four antibiotics as a rescue therapy for Helicobacter pylori eradication in the central region of Portugal

Background: Helicobacter pylori eradication rates with standard triple therapy in many countries are clinically unacceptable. Fluoroquinolone resistance is increasing and jeopardizing secondline regimens. There is a growing need for an effective strategy in patients who failed previous therapies. Methods: This is a single-center, non-randomized clinical study conducted in the central region of Portugal. Sixty-four patients were included with a positive 13C-urea breath test (UBT) or histology for H. pylori, and at least one failed eradication attempt. The patient cohort included 71.7% of females with a median of age of 52 (range 23-87). They were treated with a twelve-day regimen consisting of a proton-pump inhibitor (PPI) bid, amoxicillin at 1,000 mg 12/12h and levofloxacin at 500 mg bid during the first seven days, followed by PPI bid, clarithromycin at 500 mg 12/12 h and either tinidazole or metronidazole at 500 mg bid/tid for five days. Eradication was assessed by UBT. The local Ethics Committee approved this study. Results: Eradication therapy was prescribed due to dyspepsia (66.7%), peptic ulcer (10%) and thrombocytopenia (8.3%). The median number of failed therapies was one (range 1-4). The eradication rate was 64.6% according to an intention-to-treat analysis (95% CI: 53-77%), and 70% by the per-protocol analysis (95% CI: 58-82%). Age, smoking, indication for eradication, previous therapies and the use of a second-generation or full-dose PPI did not affect success rates. Conclusions: Even though treatment with four antibiotics was used, this «reinforced» therapy achieved suboptimal results. This fact highlights the lack of effective H. pylori antimicrobials and suggests that second-line treatment in our region should be prescribed according to susceptibility testing (AU)

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Twelve-day quintuple regime containing four antibiotics as a rescue therapy for Helicobacter pylori eradication in the central region of Portugal.

BACKGROUND: Helicobacter pylori eradication rates with standard triple therapy in many countries are clinically unacceptable. Fluoroquinolone resistance is increasing and jeopardizing second-line regimens. There is a growing need for an effective strategy in patients who failed previous therapies. METHODS: This is a single-center, non-randomized clinical study conducted in the central region of Portugal. Sixty-four patients were included with a positive 13C-urea breath test (UBT) or histology for H. pylori, and at least one failed eradication attempt. The patient cohort included 71.7% of females with a median of age of 52 (range 23-87). They were treated with a twelve-day regimen consisting of a proton-pump inhibitor (PPI) bid, amoxicillin at 1,000 mg 12/12 h and levofloxacin at 500 mg bid during the first seven days, followed by PPI bid, clarithromycin at 500 mg 12/12h and either tinidazole or metronidazole at 500 mg bid/tid for five days. Eradication was assessed by UBT. The local Ethics Committee approved this study. RESULTS: Eradication therapy was prescribed due to dyspepsia (66.7%), peptic ulcer (10%) and thrombocytopenia (8.3%). The median number of failed therapies was one (range 1-4). The eradication rate was 64.6% according to an intention-to-treat analysis (95% CI: 53-77%), and 70% by the per-protocol analysis (95% CI: 58-82%). Age, smoking, indication for eradication, previous therapies and the use of a second-generation or full-dose PPI did not affect success rates. CONCLUSIONS: Even though treatment with four antibiotics was used, this "reinforced" therapy achieved suboptimal results. This fact highlights the lack of effective H. pylori antimicrobials and suggests that second-line treatment in our region should be prescribed according to susceptibility testing.

Levofloxacin or Clarithromycin-based quadruple regimens: what is the best alternative as first-line treatment for Helicobacter pylori eradication in a country with high resistance rates for both antibiotics?

BACKGROUND: Helicobacter pylori eradication rates in Portugal are declining, due to increased resistance of this bacterium to antimicrobial agents, especially Clarithromycin. Quadruple Levofloxacin-containing regimens could be an option for first-line treatment, but its efficacy should be evaluated as fluoroquinolone resistance is rapidly increasing. Our aim was to compare the efficacy of Clarithromycin and Levofloxacin-based sequential quadruple therapies as first-line treatment options and determine factors associated with treatment failure. METHODS: A total of 200 Helicobacter pylori infected patients were retrospectively included (female 57.5%; average age: 53.2 ± 15.7) and received either 10-day sequential therapy (Proton-Pump Inhibitor + Amoxicillin 1 g bid for 5 days and Proton-Pump Inhibitor + Clarithromycin 500 mg + Metronidazole/Tinidazole 500 mg bid/tid in the following 5 days; group A) or a 10-day modified sequential therapy with Levofloxacin 500 mg id instead of Clarithromycin (group B). Eradication was confirmed with urea breath test. Variables that could influence success rate were analyzed. RESULTS: There were no differences between groups in terms of gender, age, smoking habits and indications for treatment. The eradication rate obtained with Clarithromycin-based sequential treatment was significantly higher than with Levofloxacin-based therapy (90%, CI95%: 84-96% vs. 79%, CI95%: 71-87%, p = 0.001). Using full-dose proton-pump inhibitor and high-dose Metronidazole in group A, and full-dose proton-pump inhibitor and prescription from a Gastroenterologist in group B were associated with eradication success. CONCLUSIONS: Ten-day Levofloxacin-based sequential treatment achieved inadequate efficacy rate (<80%) and should not be adopted as first-line therapy. Standard sequential therapy showed significantly better results in this naïve population. Using full-dose proton-pump inhibitor and higher doses of Metronidazole is essential to achieve such results.

Health-related quality of life and utilities in gastric premalignant conditions and malignant lesions: a multicentre study in a high prevalence country.

BACKGROUND AND AIMS: A recent review of economic studies relating to gastric cancer revealed that authors use different tests to estimate utilities in patients with and without gastric cancer. Our aim was to determine the utilities of gastric premalignant conditions and adenocarcinoma with a single standardized health measure instrument. METHODS: Cross-sectional nationwide study of patients undergoing upper endoscopy (n=1,434) using the EQ-5D-5L quality of life (QoL) questionnaire. RESULTS: According to EQ-5D-5L, utilities in individuals without gastric lesions were 0.78 (95% confidence interval: 0.76-0.80), with gastric premalignant conditions 0.79 (0.77-0.81), previously treated for gastric cancer 0.77 (0.73-0.81) and with present cancer 0.68 (0.55-0.81). Self-reported QoL according to the visual analogue scale (VAS) for the same groups were 0.67 (0.66-0.69), 0.67 (0.66-0.69), 0.62 (0.59-0.65) and 0.62 (0.54-0.70) respectively. Utilities were consistently lower in women versus men (no lesions 0.71 vs. 0.78; premalignant conditions 0.70 vs. 0.82; treated for cancer 0.72 vs. 0.78 and present cancer 0.66 vs. 0.70). CONCLUSION: The health-related QoL utilities of patients with premalignant conditions are similar to those without gastric diseases whereas patients with present cancer show decreased utilities. Moreover, women had consistently lower utilities than men. These results confirm that the use of a single standardized instrument such as the EQ-5D-5L for all stages of the gastric carcinogenesis cascade is feasible and that it captures differences between conditions and gender dissimilarities, being relevant information for authors pretending to conduct further cost-utility analysis.

A short practical approach to 24R,25-dihydroxyvitamin D3.

A synthesis of the vitamin D3 metabolite 24R,25-dihydroxyvitamin D3 (1) by Lythgoe's Wittig-Horner approach is described. The key step of the synthesis is the stereocontrolled introduction of the 24-hydroxyl group by a palladium(0)-induced [3,3]-sigmatropic rearrangement on a 22R-allylic acetate (7).

Synthesis of two carboxylic haptens for raising antibodies to 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3.

Hapten derivatives of 25-hydroxyvitamin D(3) and 1alpha,25-dihydroxyvitamin D(3) were synthesized using the Wittig-Horner approach. Both haptens bearing a carboxylic group at the side chain that can be linked to a protein for raising antibodies of potential utility for the determination of 25-hydroxyvitamin D(3), 1alpha,25-dihydroxyvitamin D(3) and 1alpha-hydroxylated vitamin D(3) analogues.