Leveraging a multivariate approach towards enhanced development of direct compression extended release tablets.

Extended release formulations play a crucial role in the pharmaceutical industry by maintaining steady plasma levels, reducing side effects, and improving therapeutic efficiency and compliance. One commonly used method to develop extended release formulations is direct compression, which offers several advantages, such as simplicity, time savings, and cost-effectiveness. However, successful direct compression-based extended release formulations require careful assessment and an understanding of the excipients' attributes. The scope of this work is the characterization of the compaction behavior of some matrix-forming agents and diluents for the development of extended release tablets. Fifteen excipients commonly used in extended release formulations were evaluated for physical, compaction and tablet properties. Powder properties (e.g., particle size, flow properties, bulk density) were evaluated and linked to the tablet's mechanical properties in a fully integrated approach, and data were analyzed by constructing a principal component analysis (PCA). Significant variability was observed among the various excipients. The present work successfully demonstrates the applicability of PCA as an effective tool for comparative analysis, pattern and clustering recognition and correlations between excipients and their properties, facilitating the development and manufacturing of direct compressible extended release formulations.

Photobiomodulation and salivary glands: a systematic review.

To date, there is no compilation of evidence-based information associating photobiomodulation effect and salivary glands. This systematic review aims to assess photobiomodulation effect of low intensity laser on salivary glands in the presence of systemic diseases. MEDLINE databases were searched in duplicate through December 2018. In vivo studies and clinical trials were included if photobiomodulation was performed in salivary glands of animal (rat or mice) or human in the presence of systemic disease. The methodological quality was assessed in duplicate using the modified Newcastle-Ottawa scale (NOS). Search strategy identified 483 potentially eligible articles, and 449 were included. The Boolean search naturally leads to a high amount of works the majority of which were excluded because the analysis of the title and abstract demonstrated it was not focusing on PBM. Only 34 studies were selected for the full-text analysis, of which 5 were excluded due to non-use of photobiomodulation, 4 due to lack of control group, 2 because they were studies of cell cultures and 1 because they did not have the total of animals used. Thus, 21 papers were included for the critical evaluation of the impact of photobiomodulation on the major salivary glands; the studies used rats (n = 10) and humans (n = 11). Although studies reported an increase in the salivary rate, decrease in pain, and increase in quality of life after the PBM, the lack of standards for the application of light and reporting of the parameters, make it hard to reproduce the results. This topic is still in need for further research.

Financial impact of sarcopenia on hospitalization costs.

BACKGROUND/OBJECTIVES: This study aims to increase knowledge regarding the association of sarcopenia with hospitalization costs among a wide-ranging sample of adult hospitalized patients. SUBJECTS/METHODS: A prospective study was conducted among hospitalized adult patients. Sarcopenia was identified according to the European Working Group on Sarcopenia in Older People, as low muscle mass, assessed by bioelectrical impedance analysis and low muscle function evaluated by handgrip strength. Hospitalization cost was calculated for each patient based on discharge diagnosis-related group codes and determined on the basis of a relative weight value. Costs were defined as the percentage of deviation from the cost of a patient with a relative weight equal to one. Multivariable linear regression models were performed to identify the factors independently associated with hospitalization costs. RESULTS: A total of 656 hospitalized patients aged ⩾18 years (24.2% sarcopenic) composed the study sample. Sarcopenia increased hospitalization costs by [euro ]1240 (95% confidence interval (CI): [euro ]596-1887) for patients aged <65 years and [euro ]721 (95% CI: [euro ]13-1429) for patients aged ⩾65 years. Sarcopenic overweight was related to an increase in hospitalization costs of [euro ]884 (95% CI: [euro ]295-1476). CONCLUSIONS: Sarcopenia is independently related to hospitalization costs. This condition is estimated to increase hospitalization costs by 58.5% for patients aged <65 years and 34% for patients aged ⩾65 years.

Sarcopenia and length of hospital stay.

BACKGROUND/OBJECTIVES: We aimed to quantify the association of sarcopenia with length of hospital stay (LOS) and to identify factors associated with sarcopenia among hospitalized patients. SUBJECTS/METHODS: A total of 655 patients composed the study sample. A longitudinal study was conducted in a University Hospital. Sarcopenia was defined, according to European Consensus criteria, as low muscle mass (bioelectrical impedance analysis) and low muscle function (handgrip strength). Logistic regression, Kaplan-Meier and Cox adjusted proportional hazards methods were used. LOS was determined from the date of hospital admission and discharge home (event of interest). RESULTS: Participants were aged 18 to 90 years (24.3% sarcopenic). Factors associated with sarcopenia were male gender, age ⩾65 years, moderate or severe dependence, undernutrition and being admitted to a medical ward. Sarcopenic patients presented a lower probability of being discharged home (hazard ratio (HR), 95% confidence interval (CI)=0.71, 0.58-0.86). However, after stratifying for age groups, this effect was visible only in patients aged <65 years (HR, 95% CI= 0.66, 0.51-0.86). Moreover, sarcopenic overweight or obese patients presented a higher probability of being discharged home (HR, 95% CI=0.78, 0.61-0.99) than nonoverweight sarcopenic patients (HR, 95% CI=0.63, 0.48-0.83). CONCLUSIONS: Being male, age ⩾65 years, presenting dependence, being undernourished and admitted to a medical ward were factors associated with sarcopenia among hospitalized adult patients. Sarcopenia is independently associated with longer LOS, although this association is stronger for patients aged <65 years. Moreover, sarcopenic overweight was associated with a higher probability of discharge home than nonoverweight sarcopenia.

Comparative analysis of undernutrition screening and diagnostic tools as predictors of hospitalisation costs.

BACKGROUND: Undernutrition is associated with higher hospitalisation costs. The present study aims (i) to explore whether undernutrition status at hospital admission, as evaluated by different screening and diagnostic tools, can predict patient's hospitalisation costs and (ii) to provide an updated economic analysis of undernutrition burden. METHODS: A prospective study was conducted in a university hospital. Participants' (n = 637) nutritional risk was evaluated within 72 h of admission using the Nutritional Risk Screening (NRS-2002) and the Malnutrition Universal Screening Tool ('MUST'). Undernutrition status was determined by Academy of Nutrition and Dietetics (AND) and American Society for Parenteral and Enteral Nutrition (ASPEN) recommended clinical characteristics and by the Patient Generated Subjective Global Assessment (PG-SGA). The hospitalisation cost was calculated for each inpatient using the diagnosis-related group system. Multivariable linear regression analysis was conducted to identify predictors of hospitalisation costs via percentage deviation from the mean cost, after adjustment for patients' characteristics and comorbidities. RESULTS: Undernutrition risk according to NRS-2002 and high undernutrition risk according to 'MUST' increased patient's costs, respectively, by 21.1% [95% confidence interval (CI) = 9.0-33.2%] and 28.8% (95% CI = 13.7-39.9%). Severe undernutrition by AND-ASPEN recommended clinical characteristics and by PG-SGA was also associated with higher hospitalisation costs, respectively 19.4% (95% CI = 7.3-31.5%) and 27.5% (95% CI = 14.0-41.1%). The cost of a nutritionally-at-risk or undernourished patient is between €416 (95% CI = €156-675) and €617 (95% CI = €293-855) higher than the average of the respective diagnosis-related group. CONCLUSIONS: Undernutrition is a predictor of hospitalisation costs, increasing costs by between 19% and 29%. Undernutrition screening tools have an ability for predicting hospitalisation costs similar to that of diagnostic tools. An updated analysis of undernutrition associated costs was provided, highlighting the economic burden of undernutrition.

Asthma control and exacerbations in patients with severe asthma treated with omalizumab in Portugal.

The analysis of outcomes from patients with severe asthma treated with omalizumab, using real-life prospective data, should contribute to future informed decisions about this treatment in Portugal. The aim of this study was to assess the clinical effect of omalizumab in Portuguese patients with severe persistent allergic asthma, considering specifically asthma control and exacerbations. This was an observational, prospective, multicentre study. Data were collected at routine care over a 12-month period. Disease control was defined by Control of Allergic Rhinitis and Asthma Test (CARAT) global score >24. All asthma patients already under treatment with omalizumab in 7 departments from 6 Portuguese hospitals were included (n=48). Most (77%) patients were female and the mean (SD) age was 51.9 (10.2) years old. During the study period, asthma was controlled in 34% of the visits and the 12-month exacerbation rate was 1.7 per patient (0.6 with unscheduled medical care). One-third of the patients needed unscheduled medical care because of asthma and 29% had to start or increase oral corticosteroid. There was still a 41% reduction in the total sum of oral corticosteroids usage from the first to the last trimester of the study. During routine treatment with omalizumab, Portuguese patients with severe asthma achieved asthma control in 1/3 of the visits and only 1/3 needed unscheduled or Emergency Room care because of asthma exacerbations. These outcomes support the maintenance of the clinical effect during treatment with omalizumab in routine care in Portugal.

Handgrip strength measurement as a predictor of hospitalization costs.

BACKGROUND: Undernutrition status at hospital admission is related to increased hospital costs. Handgrip strength (HGS) is an indicator of undernutrition, but the ability of HGS to predict hospitalization costs has yet to be studied. OBJECTIVE: To explore whether HGS measurement at hospital admission can predict patient's hospitalization costs. SUBJECTS/METHODS: A prospective study was conducted in a university hospital. Inpatient's (n=637) HGS and undernutrition status by Patient-Generated Subjective Global Assessment were ascertained. Multivariable linear regression analysis, computing HGS quartiles by sex (reference: fourth quartile, highest), was conducted in order to identify the independent predictors of hospitalization costs. Costs were evaluated through percentage deviation from the mean cost, after adjustment for patients' characteristics, disease severity and undernutrition status. RESULTS: Being in the first or second HGS quartiles at hospital admission increased patient's hospitalization costs, respectively, by 17.5% (95% confidence interval: 2.7-32.3) and 21.4% (7.5-35.3), which translated into an increase from €375 (58-692) to €458 (161-756). After the additional adjustment for undernutrition status, being in the first or second HGS quartiles had, respectively, an economic impact of 16.6% (1.9-31.2) and 20.0% (6.2-33.8), corresponding to an increase in hospitalization expenditure from €356 (41-668) to €428 (133-724). CONCLUSIONS: Low HGS at hospital admission is associated with increased hospitalization costs of between 16.6 and 20.0% after controlling for possible confounders, including undernutrition status. HGS is an inexpensive, noninvasive and easy-to-use method that has clinical potential to predict hospitalization costs.

The effect of posture on body circumferences in older adults.

BACKGROUND: Standards for anthropometrical assessment define that measurements must be carried out with the subject in the standing position, although this is not always possible. The effect of body position on girth measurement has not been evaluated, even though this issue is clinically relevant because it may bias nutritional assessment results. The present study aimed to evaluate the effect of body position and symmetry on girth measurement. METHODS: A cross-sectional study was conducted on 102 older adults aged ≥65 years from care homes and tertiary hospitals. Right and left arm, waist, hip mid-thigh and calf girths were obtained with the subject standing or in the supine position. Mini-Nutritional Assessment Short-Form (MNA-SF) score and reference data percentiles (NHANES IV) misclassification according to girths assessed in the supine position was evaluated. RESULTS: A high intraclass correlation coefficient (ICC > 0.97) and quartiles agreement (k > 0.89) were found between girth measurements conducted on participants in the standing and supine positions. According to MNA-SF, 23.5% of the participants were undernourished and 51% were at risk of undernutrition. A high agreement between MNA-SF score using calf circumference measured on standing or supine position was found (k = 0.96). A relevant agreement for NHANES IV girth percentiles by sex and age was also found (ICC > 0.89). CONCLUSIONS: Agreement between girth measurements on standing and supine positions among older adults is high and differences do not have any clinically relevant impact on MNA-SF classification and reference data percentiles.

Respiratory mechanics and morphometry after progressive intraperitoneal effusion.

Respiratory mechanics and thoraco-abdominal morphometry were evaluated in anesthetized, paralyzed, mechanically ventilated rats before and after controlled intraperitoneal injection of warm (37 degrees C) saline. Respiratory system resistances and static elastance were determined in 9 animals using the end inflation occlusion method. Chest wall configuration at both functional residual capacity (FRC) and end inspiration (FRC + VT) was evaluated in: (a) 6 rats by measurements of lateral and anteroposterior diameters, and circumferences at four levels: 3rd intercostal space, xiphoid, subcostal plane and crista iliaca; and (b) 8 rats by measurements of thoracic cephalo-caudal diameter. In addition, FRC changes were measured in 6 rats. Resistances were not altered but static elastance increased progressively. Morphometric changes were similar at both FRC and FRC + VT: cephalo-caudal diameter diminished whereas all other diameters augmented; FRC decreased. In conclusion, intraperitoneal infusion of saline in rats augments elastance, and this is related to a cephalad deviation of the diaphragm plus an increase of the circumferences and diameters of the lower thorax.

Respiratory mechanics after tube thoracostomy in rats.

The purpose of the present study was to determine the mechanical respiratory profile after the insertion of a catheter into the pleural cavity of anesthetized, paralyzed, mechanically ventilated rats, thus stimulating the common use of chest tubes in clinical situations. Using the method of end-inflation occlusion during constant inspiratory flow in 7 adult Wistar rats, respiratory system, lung, and chest wall total resistance (0.353 +/- 0.058, 0.260 +/- 0.651, 0.091 +/- 0.012 (mean +/- SD) cmH2O.ml-1.s, respectively), viscous resistance (0.140 +/- 0.007, 0.100 +/- 0.007, 0.040 +/- 0.003 cmH2O.ml-1.s< respectively), and viscoelastic resistance (0.213 +/- 0.017, 0.160 +/- 0.022, 0.053 +/- 0.011 cmH2O.ml-1.s, respectively) as well as respiratory system, lung, and chest wall static elastance (4.51 +/- 0.27, 3.85 +/- 0.28, 0.66 +/- 0.12 cmH2O.ml-1, respectively), and dynamic elastance (5.72 +/- 0.24, 4.76 +/- 0.32, 0.96 +/- 0.17 cmH2O.ml-1, respectively) were not significantly modified after the insertion of a tube into the second right intercostal stage. We conclude that, under the present experimental conditions, a catheter inserted into the pleural space per se is not responsible for any alterations in respiratory mechanics.

Respiratory mechanics after tube thoracostomy in rats

The purpose of the present study was to determine the mechanical respiratory profile after the insertion of a catheter into the pleural cavity of anesthetized, paralyzed, mechanically ventilated rats, thus simulating the common use of chest tubes in clinical situations. Using the method of end-inflation occlusion during constant inspiratory flow in 7 adult Wistar rats, respiratory system, lung, and chest wall total resistance (0.353 +/- 0.058, 0.260 +/- 0.651, 0.092 +/- 0.012 (mean +/- SD) cmH2O.ml-1.s, respectively), viscous resistance (0.140 +/- 0.007, 0.100 +/- 0.007, 0.040 +/- 0.003 cmH2O.ml-1.s, respectively), and viscoelastic resistance (0.213 +/- 0.017, 0.160 +/- 0.022, 0.053 +/- 0.011 cmH2O.ml-1.s respectively) as well as respiratory system, lung and chest wall static elastance (4.51 +/- 0.27, 3.85...

Mechanical and morphometrical changes in progressive bilateral pneumothorax and pleural effusion in normal rats.

Respiratory changes resulting from stepwise intrathoracic injections of 4 ml of either room air or warm (37 degrees C) Haemaccel, simulating pneumothorax and pleural effusion, respectively, were evaluated in anaesthetized, paralysed, and mechanically-ventilated rats. Respiratory system, lung, and chest wall resistances and elastances (static and dynamic) were determined in 14 animals. For this purpose, the end-inflation occlusion during constant inspiratory flow method was used. Chest wall configuration at both functional residual capacity (FRC) and end-inspiration tidal volume (i.e. FRC+(VT)) was also evaluated in: 1) 15 rats by measurements of lateral and anteroposterior diameters, and circumferences at the 3rd intercostal space and xiphoid levels; and 2) in 16 rats by measurements of thoracic cephalocaudal diameter. In addition, changes in functional residual capacity were measured. Both in pneumothorax and pleural effusion, resistances were not altered, but static and dynamic respiratory system and lung elastances increased progressively. Morphometric changes were similar at both functional residual capacity and end-inspiration; however, whereas pleural effusion increased all diameters, pneumothorax did not modify lateral diameter. Functional residual capacity was decreased in both conditions. In conclusion, pneumothorax and pleural effusion induced similar mechanical changes, but thoracic configuration was differently affected, since lateral diameters were increased in pleural effusion only.

Susceptibility of Candida spp. of clinical origin to lucknomycin, a new polyenic antibiotic.

Lucknomycin is a new polyenic derivative antifungal agent obtained from a Streptomyces diastatochromogenes culture. The in vitro activity of the compound was tested against 403 strains of different Candida species of clinical origin by the Sabouraud Agar dilution method. The mean geometrical value of the minimal inhibitory concentrations (MIC) for Candida albicans was 0.85 microgram/ml, 6 times lower than the corresponding value of nystatin (5.29 micrograms/ml) and very close to that of amphotericin B (0.56 microgram/ml). Lucknomycin was also 4-10 times more active than nystatin on other Candida species, with an MIC similar to those obtained with amphotericin B.

Serological tests in the diagnosis of fungal urinary tract infection.

Fungus urine cultures were performed in 646 cases. In 50 we obtained a positive result. In 35 of these and in a control group of apparently healthy adults, we made serological studies using the following techniques: Immunodiffusion; counter immunoelectrophoresis, and immunofluorescence. 4 patients has positive precipitins against somatic and metabolic antigens. We obtained histological confirmation of deep candidiasis. In another 4 patients, the precipitins were positive against metabolic antigen only and further study failed to show deep candidiasis. In a further two cases we obtained positive titers using immunofluorescence; in 1 of these deep infection was confirmed. On no occasion in our study did the use of immunodiffusion and counter immunoelectrophoresis produce either false positive or false negative results against somatic antigen.

Clinical bacteriological evaluation of infantile bacteriuria treated with fosfomycin.

The therapeutic action of fosfomycin has been studied in a group of 14 children, with simple and complicated infections of the urinary tract with congenital renal malformations. In the bacteriological study of the urine it was observed that the strains most frequently isolated were E. coli, Proteus sp. and Klebsiella sp. Of the 25 strains isolated 76% were sensitive to the disc of 50 mug fosfomycin and 24% moderately sensitive with a MIC of 64 and 128 mug/ml. The doses of fosfomycin used were 150 mg/kg/day in four administrations. In 13 cases it was administered orally alone and in one case orally and intramuscularly. The results have been good in 10 cases (71.4%) and bad in four cases. The antibiotic has shown good tolerance and no secondary effects have been noticed.

Treatment of respiratory infections with fosfomycin.

Evaluation was made of the clinical-bacteriological results of treatment with fosfomycin on a group of 27 patients with infectious respiratory pathology. The group is made up of patients with respiratory infections diagnosed as pneumonias, bronchopneumonias, acute bronchitis and chronic bronchopneumopathies. The doses of fosfomycin used varied between 4 and 12 g/day, administered during a period of 1 or 2 weeks. The results of the treatment expressed in clinical and bacteriological parameters have been successful in 15 and 21 cases for their bacteriological response and their clinical response respectively.