Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study.

AIMS: To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). RESULTS: Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74-3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31-1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08-2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment. CONCLUSIONS: BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.

Insoluble fiber sources in mash or pellets diets for young broilers. 2. Effects on gastrointestinal tract development and nutrient digestibility1.

The effects of feed form and dietary fiber on the development of the gastrointestinal tract (GIT) and nutrient digestibility were studied in broilers at 8 and 21 d of age. The experiment included 14 treatments arranged as a 2 × 7 factorial with 2 feed forms (mash vs. pellet) and 7 diets that consisted in a low fiber diet and 6 extra diets resulting from the combination of 3 insoluble fiber sources [oat hulls (OH), rice hulls, and sunflower hulls] and 2 levels of inclusion (2.5 and 5.0%). Pelleting decreased the relative weight (% BW) of the full GIT, and empty gizzard (P < 0.001) and the relative length (cm/kg empty BW) of the small intestine and ceca (P < 0.001) and increased full crop (P < 0.001) and liver (P < 0.05) weights. Fiber inclusion increased the empty weight and the fresh digesta content of the gizzard (P < 0.001) but had limited and inconsistent effects on the weight of the full GIT or the length of the small intestine and ceca. Gizzard pH decreased with mash feeding and fiber inclusion (P < 0.001). Pelleting decreased ether extract retention (P < 0.05) but did not affect N retention or AMEn of the diets. Fiber inclusion improved nutrient retention (P < 0.05 to P < 0.001) with more pronounced effects with OH than with sunflower hulls or rice hulls inclusion. The AMEn of the diets increased (P < 0.05) with 2.5% of fiber inclusion but no extra benefits were obtained with a further increase to 5.0%. Starch ileal digestibility increased with mash feeding (P < 0.001) and fiber supplementation (P < 0.05). In summary, pelleting increases full crop weight and gizzard pH and decreased full gizzard weight and starch ileal digestibility. Moderate amounts of insoluble fiber, especially OH, increases gizzard weight, reduces gizzard pH, and improves nutrient digestibility in young broilers.

Inclusion of insoluble fiber sources in mash or pellet diets for young broilers. 1. Effects on growth performance and water intake.

The effects of feed form and the inclusion of insoluble fiber in the diet on growth performance and water intake were studied in female broilers from 0 to 21 d of age. The experimental design was completely randomized with 14 treatments arranged as a 2 × 7 factorial with 2 feed forms (mash vs. pelleted) and 7 diets that consisted of a control diet low in fiber (1.6% crude fiber) based on broken rice, fermented soybean meal, and fish meal and 6 extra diets that resulted from the inclusion of 3 insoluble fiber sources (oat hulls; OH, rice hulls; RH, and sunflower hulls; SFH) at 2 levels (2.5 vs. 5%). Each treatment was replicated 6 times. Broilers fed pellets had 32% greater ADG and 3% better feed to gain ratio (F:G) than those fed mash (P ≤ 0.001). The inclusion of the fiber sources improved ADG (P ≤ 0.05) and F:G (P ≤ 0.05). Pelleting increased (P ≤ 0.001) water intake from 6 to 8 d, water-to-feed intake ratio from 18 to 20 d, and moisture content of the excreta at 20 d of age. The inclusion of the insoluble fiber sources increased water intake (P ≤ 0.05) from d 18 to 20 but not from d 6 to 8. Increasing the level of fiber inclusion from 2.5 to 5.0% tended to increase (P = 0.086) moisture content in the excreta at d 20. Pelleting and the inclusion of insoluble fiber sources improved ADG and F:G in broilers fed low-fiber diets, and the improvements observed were more pronounced with pellets than with mash. Growth performance of young broilers improves with the addition of moderate amounts of structural insoluble fiber in the diet, regardless of feed form. The inclusion of OH or SFH into low fiber diets was more beneficial for improving broiler performance than the inclusion of RH.

Improving preoperative medication instructions and patient adherence: a collaborative, hospital-based quality improvement project.

The goal of this project was to improve preoperative medication instructions. After baseline data were collected prospectively through standardised patient surveys, preoperative care providers were educated to convey clear, appropriate preoperative medication instructions. After the education period, patient surveys were again completed to assess improvement. Hospital-wide education effectively increased the percentage of medications with written, colour-coded, and medically appropriate instructions. Patients found the instructions clearer and easier to follow.

On the Incorrect Statistical Calculations of the Kinetica Software Package in Imbalanced Designs.

This regulatory note supports the previous findings that suggest that the software package Kinetica, up to version 5.0.10, provides incorrect results for the 90% confidence intervals for the ratio test/reference where the groups are imbalanced in 2 × 2 crossover designs and parallel designs. The incorrect calculation results from using the simplified formula that is shown as an example in the Canadian guideline for a balanced dataset, but which provides an erroneous point estimate and confidence interval width in cases of imbalanced designs. Importantly, this software is rarely used for regulatory submissions in the European Union according to the search conducted in the Spanish Agency for Medicines and Health Care Products. According to our data, the error is minor if the imbalance between groups is small. However, the error may be relevant if the sample size is small and the imbalance is large. Therefore, bioequivalence studies should be reanalyzed by regulatory agencies to confirm the submitted results.

Effects of type and particle size of dietary fiber on growth performance and digestive traits of broilers from 1 to 21 days of age.

A trial was conducted to study the effects of type and particle size of dietary fiber on growth performance and digestive traits of broilers from 1 to 21 d of age. There was a negative control diet with 1.54% crude fiber, a positive control diet that included 3% cellulose (CEL), and 4 additional diets arranged factorially that included 3% oat hulls (OH) or sugar beet pulp (SBP) ground through a 0.5- or a 2.0-mm screen. For the entire experimental period, fiber inclusion improved BW gain (P≤0.01) and feed conversion ratio (P≤0.001), but particle size of the fiber source did not affect performance. The relative weight of the gizzard was higher (P≤0.001) with OH and SBP than with CEL or the control diet. Also, gizzard weight decreased (P≤0.001) with a reduction in particle size of the fiber source. Fiber inclusion increased HCl concentration and reduced gizzard pH (P≤0.01), and the effects were more noticeable with OH and SBP than with CEL. Fiber inclusion increased total tract apparent retention of nitrogen (P≤0.001) and soluble ash (P≤0.001) as well as the AMEn of the diet (P≤0.001). All of these effects were in general more pronounced with OH than with CEL, with SBP being intermediate. A reduction in particle size of the OH and SBP improved total tract apparent retention of DM (P≤0.001), nitrogen (P≤0.05), and soluble ash (P≤0.01) as well as the AMEn of the diet (P≤0.05). It is concluded that additional OH and SBP improves gizzard weight and growth performance in young chicks fed low-fiber diets and that the effects are more pronounced with OH than with CEL. Particle size of OH and SBP does not affect broiler performance, but coarse grinding increases gizzard development and reduces nutrient digestibility in young birds.

Influence of source of soybean meal and lysine content of the diet on performance and total tract apparent retention of nutrients in broilers from 1 to 36 days of age.

The influence of soybean meal (SBM) source and total Lys content of the diet on performance and total tract apparent retention of nutrients was evaluated in broilers from 1 to 36 d of age. There were 6 treatments arranged factorially with 2 sources of SBM [regular SBM with 46.3% CP (R-SBM) and high-protein SBM with 48.6% CP (HP-SBM)] and 3 Lys:AME(n) ratios (Lys:ME; 380, 415, and 450 mg of total Lys:1,000 kcal of AME(n) from 1 to 21 d; and 312, 338, and 364 mg of total Lys:1,000 kcal of AME(n) from 22 to 36 d of age). From 1 to 36 d of age, broilers fed the HP-SBM diets had higher ADG and better feed:gain ratio (F:G) than broilers fed the R-SBM diets (P < or = 0.001). Both ADG and F:G improved (P < or = 0.05) with increases in the Lys:ME ratio. From 1 to 21 d of age, ADG and F:G (P < or = 0.001) were improved when the Lys:ME ratio increased and the benefits were more pronounced with the diets based on R-SBM. From 22 to 36 d of age, increasing the Lys:ME ratio from 312 to 338 increased ADG (P < or = 0.05) and F:G (P < or = 0.01), but no further improvements were observed when the ratio was increased to 364. The total tract apparent retention of DM and gross energy of the diets were higher (P < or = 0.05) for the HP-SBM than for the R-SBM diets. An increase in the Lys:ME ratio reduced organic matter and N retention (P < or = 0.05). The improvements in growth performance and nutrient retention observed in broilers fed the HP-SBM diets with respect to those fed the R-SBM are consistent with a better availability of nutrients of the high-protein meal. In addition, the results indicate that Lys requirements of broilers are at least, 30, 20, and 8% higher from 1 to 10, 10 to 21, and 21 to 36 d of age, respectively, than current NRC recommendations.

Effect of dietary fiber and fat on performance and digestive traits of broilers from one to twenty-one days of age.

The influence of fiber source and dietary fat level on digestive traits and productive performance was studied in broilers from 1 to 21 d of age. There were 6 treatments arranged factorially with 3 sources of fiber (none; 3% oat hulls, OH; and 3% sugar beet pulp, SBP) and 2 fat sources (5% soybean oil, SO; and 5% yellow grease, YG). Each treatment was replicated 6 times and the experimental unit was a cage with 18 broilers. Fiber inclusion improved BW gain (P < or = 0.05) and feed:gain ratio (P < or = 0.001) and increased total tract apparent retention (TTAR) of all nutrients measured (P < or = 0.001). The increases observed in TTAR of nitrogen and ether extract and on AME(n) of the diet were more pronounced with OH than with SBP. The increases in nutrient digestibility with OH inclusion were higher at excreta than at ileal level and in fact, SBP inclusion reduced the apparent ileal digestibility of most nutrients. The relative weight (%) of the gizzard was increased (P < or = 0.001) and the pH of its contents was reduced (P < or = 0.001) when additional fiber was included in the diet. The TTAR of nutrients was higher for the SO than for the YG diets (P < or = 0.001). Also, the increases in ether extract digestibility (P < or = 0.05) and AME(n) (P < or = 0.05) of the diet with fiber inclusion were more pronounced with the YG than with the SO. Therefore, the inclusion of moderate amounts of fiber in the diet might improve performance and nutrient digestibility in young chicks, especially when saturated fats are used.

Effects of type of cereal, heat processing of the cereal, and fiber inclusion in the diet on gizzard pH and nutrient utilization in broilers at different ages.

An experiment was conducted to study the effects of type of cereal (60% corn or 60% rice), heat processing of the cereal (raw or steam-cooked), and fiber source (control without hulls, 3% oat hulls, and 3% soy hulls) on gizzard pH and total tract apparent retention (TTAR) of nutrients in broilers at different ages. There were 12 treatments arranged factorially (2x2x3) and 6 replicates (8 chicks) per treatment. The 2 basal diets were based on soy protein concentrate and fish meal and had a neutral detergent fiber content of 3.5% for the rice and 7.3% for the corn diet. Gizzard pH was lower at 13 d than at 8 or 20 d of age (P

Effects of fiber source and heat processing of the cereal on the development and pH of the gastrointestinal tract of broilers fed diets based on corn or rice.

We studied the influence of the cereal (corn and rice), heat processing (HP) of the cereal (raw and steam cooking), and fiber inclusion (none; 3% oat hulls, OH; and 3% soy hulls, SH) in low-fiber diets on the development and pH of the digestive tract in broilers. There were 12 treatments arranged factorially and 3 replicates (a cage with 12 chicks) per treatment. Digestive traits were measured at 1, 5, 9, 15, and 22 d of age, and digesta pH was determined at 22 d of age. The relative weight (% BW) of proventriculus and gizzard was greater in chicks fed corn than in chicks fed rice (P < or = 0.01). Heat processing had little effect on relative weight (RW) of the digestive organs. An interaction between cereal and HP of the cereal was detected for the gizzard and the liver; HP of corn reduced RW of the gizzard and increased that of the liver, but no effect was observed with HP of rice. The RW of the proventriculus was increased by SH inclusion (P < or = 0.05), whereas the RW of the gizzard was increased by OH inclusion (P < or = 0.001). Also, SH inclusion increased gizzard digesta (P < or = 0.01) and moisture (P < or = 0.001) content. Dietary treatment did not affect relative length (cm/kg of empty BW) of the intestines. Feeding rice tended to increase gizzard digesta pH (P = 0.081) but reduced that of the intestines (P < or = 0.001). Neither HP of the cereal nor hull inclusion affected pH of the digestive tract. We conclude that the RW of the proventriculus and gizzard is reduced by feeding rice and increased by hull inclusion. Dietary treatment had little effect on the weight and relative length of the intestines. Chicks might require a minimal amount of fiber in the diet to stimulate the development of the upper gastrointestinal tract.

Effect of type of cereal, heat processing of the cereal, and inclusion of fiber in the diet on productive performance and digestive traits of broilers.

We studied the influence of cereal, heat processing of the cereal, and inclusion of additional fiber in the diet on the productive performance and digestive traits of broilers from 1 to 21 d of age. Twelve treatments were arranged factorially, with 2 cereals (corn and rice), 2 heat-processing treatments of the cereals (raw and cooked), and 3 sources of fiber (none, 3% oat hulls, and 3% soy hulls). Each treatment was replicated 6 (trial 1) or 3 (trial 2) times. Growth traits were recorded in both trials; digestive traits were measured in trial 1, and total tract apparent retention (TTAR) of nutrients was determined in trial 2. Feeding rice improved TTAR of all nutrients and feed conversion from 1 to 21 d of age (P

Case of Staphylococcus schleiferi subspecies coagulans endocarditis and metastatic infection in an immune compromised host.

Staphylococcus schleiferi subspecies coagulans is a relatively recently described organism with limited human pathogenicity. Described case reports of infection are primarily limited to canine external otitis with only one reported case of human involvement, localized to a surgical wound infection. Similarities in phenotypic and microbiological characteristics between S. schleiferi subsp. coagulans and S. aureus have resulted in frequent mistakes using common methods of identification. We describe the first case of disseminated human infection with this species, definitively identified using DNA sequencing, and successfully treated with conventional therapy.

[Population density, total population, and levels of demographic aging in the province of Guadalajara (Spain) in 1981]. / Densidades, poblacion absoluta, y grados de envejecimiento de la poblacion en la provincia de Guadalajara (Espana) en 1981.

PIP: This report contains tables, charts, and maps showing the effects of migration to Madrid on the age structure, density, and geographic distribution of the population of the province of Guadalajara, Spain. The focus is on the period 1960-1981 (SUMMARY IN ENG)^ieng