Does simultaneous administration of a PGE1 analog prevent indomethacin damage to human gastric mucosa? An endoscopic double-blind study

The influence on gastroduodenal mucosa of indomethacin (50 mg t.i.d.) administration for 6 days was investigated in 7 healthy volunteers in a double-blind randomized crossover study with and without concomitant administration of MDL 646, 400 micrograms q.i.d. and 800 micrograms q.i.d. Indomethacin induced a gastroduodenal lesion index of 2.4 +/- 0.1. Neither of the prostaglandin E1-analogue dosages afforded significant protection of gastric and duodenal mucosa (2.1 +/- 0.4 in the presence of 400 micrograms q.i.d. and 1.9 +/- 0.4 in the presence of 800 micrograms q.i.d.). Major side effects were not observed.     

The effects of oral rabeprazole on endocrine and gastric secretory function in healthy volunteers

AIM: To evaluate the short-term effects of rabeprazole 20 mg on endocrine parameters, in particular serum testosterone and cortisol, and on 24 h intragastric pH, H+ activity and nocturnal gastric acid secretion. METHODS: In this double-blind, two-period crossover study, 12 healthy young male volunteers were randomly given oral rabeprazole 20 mg o.m. or placebo for 14 days. There was a washout period of at least 1 week between the two studies. The effects of rabeprazole and placebo on cortisol and testosterone (primary criteria), and on tri-iodothyronine, thyroxine, 17beta-oestradiol, thyroid-stimulating hormone, thyroxine-binding protein, parathyroid hormone, insulin, glucagon, rennin, aldosterone, follicle-stimulating hormone, luteotrophic hormone, prolactin, somatotrophic hormone, dehydroepiandrosterone, cortisol-binding globulin and urinary 6-beta hydroxycortisol were compared. Intragastric 24 h pH, 24 h H+ activity and nocturnal gastric acid secretion were determined by pH probe and gastric aspiration. RESULTS: Rabeprazole produced no clinically relevant effects on endocrine function as assessed by measurement of serum testosterone, circadian serum cortisol levels, ACTH-stimulated serum cortisol levels and 17 other endocrine function tests. Rabeprazole significantly increased the 24 h median pH values compared to placebo (on Days 7 and 14 median values ranged from 3.92 to 6.88 with rabeprazole and from 1.48 and 4.22 with placebo, P < 0.001) and significantly decreased the integrated 24 h H+ activity (AUC08--08) from 343 mmol/L/h with placebo to 44 mmol/L/h with rabeprazole (P < 0.001). Following cessation of dosing, intragastric pH levels decreased and H+ activity increased, but acid secretion did not recover completely during the next 72 h. The mean value for nocturnal gastric acid secretion on Days 7 and 8 was 36 mmol/6 h with placebo and 5.6 mmol/6 h with rabeprazole (P < 0.001). Rabeprazole was well tolerated. CONCLUSION: Rabeprazole did not influence endocrine function in healthy young male volunteers during short-term dosing. Rabeprazole substantially increased intragastric pH over a 24 h period and significantly decreased intragastric acidity and nocturnal gastric acid secretion.     

Computer-aided surgical planning for implantation of hearing aids based on CT data in a VR environment.

A study was undertaken to assess the feasibility of a preoperative fitting test for an implantable hearing aid in a virtual reality (VR) environment. High-resolution spiral computed tomography (CT) of the mastoid bone was performed, and the results of a mastoidectomy were simulated with manual segmentation on a standard medical workstation. CT was also performed on a temporal bone specimen obtained at real mastoidectomy, and the bone margins were segmented automatically with threshold-based techniques. A triangulated surface representation of the bone structures including the mastoid cavity was generated. These data as well as the computer-aided design (CAD) files of the medical devices were transferred into a VR environment. The CAD components of the hearing aid were manipulated to simulate the surgical implantation procedure. Merging CAD data of an implantable hearing aid with CT data of the temporal bone in a VR environment was shown to be a feasible method of providing three-dimensional information for the presurgical determination of fit and mountability. Advances in hardware and software are expected to improve the usability of this method. Although clinical studies are needed, these results may serve as an impetus for exploring the use of low-cost, widely available VR computer equipment in a potentially broad field of clinical applications.     

Intragastric acidity under the prostaglandin E2 analog trimoprostil. Increased inhibitory effect through administration after meals

In this double-blind cross-over study the effect of trimoprostil (trimethyldesoxyprostaglandin E2), an orally effective prostaglandin E2 analogue, on 24-h intragastric H+-activity, nocturnal acid output, nocturnal volume secretion and meal stimulated gastrin secretion was determined in 12 healthy male volunteers. On three different days the subjects received four times a day either placebo or 1.5 mg trimoprostil 30 min before or 30 min after meals. Trimoprostil administered before or after meals reduced 24-h intragastric acidity by 27.0 and 53.9%. Nocturnal acid output was inhibited by 32.7 and 55.6%. Nocturnal volume secretion and meal stimulated gastrin secretion remained unaffected. The study shows that the antisecretory activity is significantly increased when trimoprostil is given after meals.     

Protective effect of an antacid against acetylsalicylic acid

The protective action of an magnesium-aluminum-antacid (Mucal-Gel) against acute doses of acetylsalicylic acid (ASA) was studied in healthy subjects (n = 30) by a double-blind cross-over method. The severity of the lesion was determined by endoscopy. In the corresponding placebo experiments, severe lesions of the gastroduodenal mucosa were seen after administration of 1500 mg ASA. These lesions could be prevented only in the presence of high doses of the antacidum mixture. It is concluded from these studies that protective actions against ASA can be achieved only if the intragastric pH-level is adequately raised above 3.5 and higher.     

Health and nutritional status of Wistar rats following subchronic exposure to CV127 soybeans

This subchronic duration feeding study evaluated the nutritional and health status of rats fed diets containing CV127 at incorporation levels of 11% and 33%. For control comparisons, rats were also exposed to similar incorporation levels of the near isogenic conventional soybean variety (Conquista) and two other conventional soybean varieties (Monsoy, Coodetec). In spite of phenotypic differences among these four soybean varieties, there were no quantitative differences in their respective proximate and other compositional properties, including proteins, amino acids, antinutrients and nutritional cofactors. All diets were prepared by blending the respective processed soybean meal with ground Kliba maintenance meal at high (33%) and low (11%) incorporation levels, and the blended diets were fed to Wistar rats for about 91 days. Although there were some isolated parameters indicating statistically significant changes, these lacked consistency and a plausible mechanism and were thus assessed to be incidental. The totality of results demonstrate that CV127 soybeans are similar with respect to their nutritional value and systemic effects as its near isogenic conventional counterpart, as well as other conventional soybean varieties. Hence, introduction of AHAS gene into soybeans does not substantially alter its compositional properties, nor adversely affect its nutritional or safety status to mammals.     

Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex

Anatomical alterations in the medial prefrontal cortex (mPFC) are associated with hypothalamopituitary adrenal (HPA) axis dysregulation, altered stress hormone levels, and psychiatric symptoms of stress-related mental illnesses. Functional imaging studies reveal impairment and shrinkage of the mPFC in such conditions, and these findings are paralleled by experimental studies showing dendritic retraction and spine loss following repeated stress in rodents. Here we extend this characterization to how repeated stress affects dendritic spine morphology in mPFC through the utilization of an automated approach that rapidly digitizes, reconstructs three dimensionally, and calculates geometric features of neurons. Rats were perfused after being subjected to 3 weeks of daily restraint stress (6 hours/day), and intracellular injections of Lucifer Yellow were made in layer II/III pyramidal neurons in the dorsal mPFC. To reveal spines in all angles of orientation, deconvolved high-resolution confocal laser scanning microscopy image stacks of dendritic segments were reconstructed and analyzed for spine volume, surface area, and length using a Rayburst-based automated approach (8,091 and 8,987 spines for control and stress, respectively). We found that repeated stress results in an overall decrease in mean dendritic spine volume and surface area, which was most pronounced in the distal portion of apical dendritic fields. Moreover, we observed an overall shift in the population of spines, manifested by a reduction in large spines and an increase in small spines. These results suggest a failure of spines to mature and stabilize following repeated stress and are likely to have major repercussions on function, receptor expression, and synaptic efficacy.     

Comparing radiographic scores for prediction of complications and outcome of aneurysmal subarachnoid hemorrhage: Which performs best?

Background and purpose

Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by high morbidity and mortality proceeding from the initial severity and following complications of aSAH. Various scores have been developed to predict these risks. We aimed to analyze the clinical value of different radiographic scores for prognostication of aSAH outcome.

Methods

Initial computed tomography scans (≤48 h after ictus) of 745 aSAH cases treated between January 2003 and June 2016 were reviewed with regard to Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), and Claassen, Barrow Neurological Institute (BNI), Hijdra, original Graeb and Fisher scale scores. The primary endpoints were development of delayed cerebral ischemia (DCI), in-hospital mortality and unfavorable outcome (modified Rankin Scale score >3) at 6 months after subarachnoid hemorrhage. Secondary endpoints included the different complications that can occur during aSAH. Clinically relevant cutoffs were defined using receiver-operating characteristic curves. The radiographic scores with the highest values for area under the curve (AUC) were included in the final multivariate analysis.

Results

The Hijdra sum score had the most accurate predictive value and independent associations with all primary endpoints: DCI (AUC 0.678, adjusted odds ratio [aOR] 2.83; p < 0.0001); in-hospital mortality (AUC 0.704, aOR 2.83; p < 0.0001) and unfavorable outcome (AUC 0.726, aOR 2.91; p < 0.0001). Multivariate analyses confirmed the independent predictive value of the radiographic scales for risk of decompressive craniectomy (SEBES and Fisher score), cerebral vasospasm (SEBES, BNI score and Fisher score) and shunt dependency (Hijdra ventricle score and Fisher score) after aSAH.

Conclusions

Initial radiographic severity of aSAH was independently associated with occurrence of different complications during aSAH and the final outcome. The Hijdra sum score showed the highest diagnostic accuracy and robust predictive value for early detection of risk of DCI, in-hospital mortality and unfavorable outcome after aSAH.     

The role of payment and financing in achieving health equity

Objective

The aim was to identify healthcare payment and financing reforms to promote health equity and ways that the Agency for Healthcare Research and Quality (AHRQ) may promote those reforms.

Data Sources and Study Setting

AHRQ convened a payment and financing workgroup–the authors of this paper–as part of its Health Equity Summit held in July 2022. This workgroup drew from its collective experience with healthcare payment and financing reform, as well as feedback from participants in a session at the Health Equity Summit, to identify the evidence base and promising paths for reforms to promote health equity.

Study Design

The payment and financing workgroup developed an outline of reforms to promote health equity, presented the outline to participants in the payment and financing session of the July 2022 AHRQ Health Equity Summit, and integrated feedback from the participants.

Data Collection/Extraction Methods

This paper did not require novel data collection; the authors collected the data from the existing evidence base.

Principal Findings

The paper outlines root causes of health inequity and corresponding potential reforms in five domains: (1) the differential distribution of resources between healthcare providers serving different communities, (2) scarcity of financing for populations most in need, (3) lack of integration/accountability, (4) patient cost barriers to care, and (5) bias in provider behavior and diagnostic tools.

Conclusions

Additional research is necessary to determine whether the proposed reforms are effective in promoting health equity.