Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

Implementation of an open fracture quality improvement intervention to improve functional outcomes following an open tibia fracture in Malawi: results of a pre-post evaluation

No abstract available

Real-world Evidence of the Effects of Novel Treatments for COVID-19 on Mortality: A Nationwide Comparative Cohort Study of Hospitalized Patients in the First, Second, Third, and Fourth Waves in the Netherlands

Background Large clinical trials on drugs for hospitalized coronavirus disease 2019 (COVID-19) patients have shown significant effects on mortality. There may be a discrepancy with the observed real-world effect. We describe the clinical characteristics and outcomes of hospitalized COVID-19 patients in the Netherlands during 4 pandemic waves and analyze the association of the newly introduced treatments with mortality, intensive care unit (ICU) admission, and discharge alive. Methods We conducted a nationwide retrospective analysis of hospitalized COVID-19 patients between February 27, 2020, and December 31, 2021. Patients were categorized into waves and into treatment groups (hydroxychloroquine, remdesivir, neutralizing severe acute respiratory syndrome coronavirus 2 monoclonal antibodies, corticosteroids, and interleukin [IL]-6 antagonists). Four types of Cox regression analyses were used: unadjusted, adjusted, propensity matched, and propensity weighted. Results Among 5643 patients from 11 hospitals, we observed a changing epidemiology during 4 pandemic waves, with a decrease in median age (67-64 years; P < .001), in in-hospital mortality on the ward (21%-15%; P < .001), and a trend in the ICU (24%-16%; P = .148). In ward patients, hydroxychloroquine was associated with increased mortality (1.54; 95% CI, 1.22-1.96), and remdesivir was associated with a higher rate of discharge alive within 29 days (1.16; 95% CI, 1.03-1.31). Corticosteroids were associated with a decrease in mortality (0.82; 95% CI, 0.69-0.96); the results of IL-6 antagonists were inconclusive. In patients directly admitted to the ICU, hydroxychloroquine, corticosteroids, and IL-6 antagonists were not associated with decreased mortality. Conclusions Both remdesivir and corticosteroids were associated with better outcomes in ward patients with COVID-19. Continuous evaluation of real-world treatment effects is needed.Immunogenetics and cellular immunology of bacterial infectious disease

Real-world Evidence of the Effects of Novel Treatments for COVID-19 on Mortality: A Nationwide Comparative Cohort Study of Hospitalized Patients in the First, Second, Third, and Fourth Waves in the Netherlands

Background Large clinical trials on drugs for hospitalized coronavirus disease 2019 (COVID-19) patients have shown significant effects on mortality. There may be a discrepancy with the observed real-world effect. We describe the clinical characteristics and outcomes of hospitalized COVID-19 patients in the Netherlands during 4 pandemic waves and analyze the association of the newly introduced treatments with mortality, intensive care unit (ICU) admission, and discharge alive. Methods We conducted a nationwide retrospective analysis of hospitalized COVID-19 patients between February 27, 2020, and December 31, 2021. Patients were categorized into waves and into treatment groups (hydroxychloroquine, remdesivir, neutralizing severe acute respiratory syndrome coronavirus 2 monoclonal antibodies, corticosteroids, and interleukin [IL]-6 antagonists). Four types of Cox regression analyses were used: unadjusted, adjusted, propensity matched, and propensity weighted. Results Among 5643 patients from 11 hospitals, we observed a changing epidemiology during 4 pandemic waves, with a decrease in median age (67-64 years; P < .001), in in-hospital mortality on the ward (21%-15%; P < .001), and a trend in the ICU (24%-16%; P = .148). In ward patients, hydroxychloroquine was associated with increased mortality (1.54; 95% CI, 1.22-1.96), and remdesivir was associated with a higher rate of discharge alive within 29 days (1.16; 95% CI, 1.03-1.31). Corticosteroids were associated with a decrease in mortality (0.82; 95% CI, 0.69-0.96); the results of IL-6 antagonists were inconclusive. In patients directly admitted to the ICU, hydroxychloroquine, corticosteroids, and IL-6 antagonists were not associated with decreased mortality. Conclusions Both remdesivir and corticosteroids were associated with better outcomes in ward patients with COVID-19. Continuous evaluation of real-world treatment effects is needed

Hipovitaminose A e anemia ferropriva em gestantes de duas comunidades do Vale do Ribeira (Estado de São Paulo, Brasil) Vitamin A deficiency and iron deficiency anemia in pregnant women of two communities of the Ribeira River Valley (State of S. Paulo, Brazil)

Com o objetivo de estudar deficiências de vitamina A e de ferro em mulheres grávidas, a nível de comunidade, estudou-se 60 gestantes, residentes na zona urbana de Apiaí e Ribeira (Estado de São Paulo), através de inquérito bioquímico, realizando-se dosagens séricas de beta-caroteno, vitamina A, hemoglobina, ferro sérico e capacidade de ligação de ferro, bem como determinação do hematócrito. Os resultados foram comentados e apontaram não haver hipovitaminose A nesta amostra, apesar de haver grande proporção de resultados de caroteno sérico considerados não-normais. Houve maior prevalência de anemia entre gestantes de Ribeira. A comparação dos resultados obtidos entre as gestantes com respectivos grupos-testemunha, apontou freqüência maior de casos considerados não-normais entre as primeiras, em todos os coeficientes levantados.<br>The present study was carried out on sixty pregnant women residing in the urban area of the cities of Apiaí and Ribeira, State of S. Paulo. Samples were taken from each subject in order to study blood levels of beta-carotene, vitamin A, hemoglobin, serum iron and iron binding capacity as well as packed cell volume, with the objective of studying vitamin A and iron deficiency. The results showed that vitamin A deficiency was absent although a large proportion of carotene levels was abnormal. Regarding anemia, prevalence was higher in Ribeira residents. Refering all results to a control group, it was found that frequency was higher in the sample subjects

The Production of Polyclonal Antibodies in Laboratory Animals

This is the report of the thirty-fifth of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM\u27s main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well-informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organisation of ECVAM workshops on specific topics, at which small groups of invited experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward (1)

The effectiveness of anxiety treatment on alcohol-dependent patients with a comorbid phobic disorder: a randomized controlled trial

Objective: Evidence has emerged which indicates that the post-treatment relapse rate for alcohol-dependent patients with a comorbid anxiety disorder is higher than for alcohol-dependent patients without a comorbid anxiety disorder. The question raised by this evidence is whether the relapse rate in these dually diagnosed patients could be reduced if they were given additional treatment for the comorbid anxiety disorder. We attempted to answer this question by conducting a trial among patients with a double diagnosis of alcohol dependence and agoraphobia or social phobia. Method: We conducted a 32-week randomized controlled trial among 96 abstinent patients with a primary diagnosis of alcohol dependence and a comorbid anxiety disorder involving agoraphobia or social phobia. The patients were randomly assigned to an intensive psychosocial relapse-prevention program on its own (n = 49) or in combination with an anxiety treatment program comprising cognitive behavioral therapy (CBT) and optional pharmacotherapy consisting of an SSRI (n = 47). The primary outcome measure was the percentage of patients who suffered an alcohol relapse during a 32-week period. The secondary outcome measures were total abstinence, a reduction in the days of heavy drinking, and less severe anxiety symptoms. Results: Although the additional therapy clearly reduced the anxiety symptoms, it had no significant effect on the alcohol relapse rates. Conclusion: Anxiety treatment for alcohol-dependent patients with a comorbid anxiety disorder can alleviate anxiety symptoms, but it has no significant effect on the outcome of alcohol treatment program