Predictive value of the Global Activity Limitation Indicator (GALI) on all-cause mortality.

OBJECTIVES: The Global Activity Limitation Indicator (GALI) is an instrument that measures long-term overall disability. The objective of this study was to evaluate GALI's predictive value on mortality while examining variations according to sex, age, and educational level. STUDY DESIGN: Longitudinal study. METHODS: This longitudinal study was based on 42,991 individuals aged ≥15 years who participated in the 2011-2012 National Health Survey and the 2014 European Health Survey in Spain. These records were linked to mortality data up to December 2021. GALI assessed self-reported functional limitation in the past 6 months and classified individuals into three categories: severely limited, limited but not severely, and not limited. Incidence rate ratios (IRR) were calculated using Poisson regression models, adjusting for sociodemographic, lifestyle, and health status variables. RESULTS: Compared to individuals with no limitations, those with non-severe limitations had an IRR for mortality of 1.27 (95% CI: 1.16-1.38), and 2.04 (95% CI: 1.81-2.31) in those with severe limitations. Women with severe limitations exhibited a higher IRR (2.32; 95% CI: 1.98-2.71) compared to men (1.73; 95% CI: 1.45-2.08) (P for interaction = 0.005). Individuals <65 years with severe limitations showed a greater association (2.22; 95% CI: 1.58-3.10) than those ≥65 (1.49; 95% CI: 1.32-1.69) (P for interaction <0.001). Among individuals with lower educational attainment, the IRR was 2.08 (95% CI: 1.83-2.37), and 1.87 (95% CI: 1.37-2.56) for the higher education group (P for interaction = 0.017). CONCLUSIONS: GALI is a robust predictor of all-cause mortality in the general population and subgroups. The association is stronger in women, individuals <65 years, and those with lower educational levels.

Ultrasound examination of the cervix for predicting labor induction success: failed validation in a routine clinical setting of a successful previous pilot study.

BACKGROUND: Induction of labor (IL) involves an overload of work in hospitals, as well as increased intervention. Traditionally, the Bishop score (BS) has been used to predict the outcome of a IL, but there is a growing interest in studying the predictive capacity of ultrasound variables. OBJECTIVE: Validate a pilot predictive model performed by a single observer (Alvarez-Colomo C), based on clinical parameters and ultrasound parameters, that showed a significant association with the IL result, obtaining a correct prediction of vaginal delivery in 82.8%, with 15% false positive (FP). This validation was carried out under the usual conditions of clinical practice by four observers without distinction. METHODS: A prospective, observational study was conducted between September 2010-July 2012, recruiting 231 single pregnancies (Group 2), who were to initiate the IL process, according to the methodology and inclusion criteria of the Alvarez-Colomo study (Group 1151 patients). The outcome variable was the method of delivery. RESULTS: Only fetal head-perineal distance (FHPD), cervical length (CL) and BS showed significant association with the result of IL. After applying the logistic regression equation of the pilot study, the model developed by these four observers reached a predictive capacity of 70.74% (FP = 20%). Clinical characteristics were similar in both groups. Statistically significant differences were found between the two groups for: FHPD, posterior cervical angle (PCA) and funnel existence. CONCLUSION: It has not been possible to validate the mathematical model of Alvarez's study in the daily conditions of clinical practice, probably due to differences in the ultrasound measurement of FHPD.

Oral pentobarbital suspension for children sedation during MR imaging.

OBJECTIVES: The efficacy and safety of an oral pentobarbital suspension for sedation during pediatric MR imaging were assessed. METHODS: Data were recorded from October 2016 to January 2017. The exact dose of oral pentobarbital suspension was given for each child with an oral syringe. Parameters recorded included the patient's age and weight, the time required to sedate, the duration of sedation, the time required to discharge, and quality of MR imaging. The adverse effects were recorded. RESULTS: Oral pentobarbital suspension was administered to 81 children aged from 8 months to 8 years at a dose of 5mg/kg of body weight. The mean time required to sedate was 30±21min, a mean time of sedation of 47±23min, and a mean time to discharge of 77±32min. Sedation occurred a satisfied quality of MR imaging in 67% of patients. The failure of examination was essentially due to bad taste of the drug suspension. The overall success rate of sedation in patients less than 12 months was 100%. For ages 1 to 3 years, the success rate decreased to 76% and for ages 4 to 8 years, it decreased to 42%. CONCLUSIONS: Oral pentobarbital suspension used in MR imaging demonstrated its high rate of successful sedation in infants less than 12 months with no adverse effects during the study period.

[Which useful Apps are installed on my smartphone as a clinical pharmacist?] / Quelles Apps utiles sur mon smartphone de pharmacien clinicien ?

Since the advent of PDAs (Personal Digital Assistants), smartphones and Apps have been widely adopted by medical professionals. This craze has increased since 2007 and the first generation iPhone. In this context, 3 questions emerged for the pharmacist that we studied in this review: (1) What Apps are available for practice and how to find them? (2) What is useful for practice? (3) What precautions should be taken?

[Oral administration of medications to infants: Implementation of a preliminary risk analysis in a hospital service of pediatrics]. / Administration orale de médicaments au nourrisson : réalisation d'une analyse préliminaire des risques dans un service d'hospitalisation pédiatrique.

PURPOSE: The objective of this study was to reduce the risk of errors when administering oral medications to infants aged 28 days to 2 years. MATERIAL AND METHODS: The method of the preliminary risk analysis (PRA) was implemented by a multidisciplinary group in a hospital service of pediatrics. The study focused on the phase of preparation of drugs by nurses before administration. RESULTS: This analysis revealed 41 scenari, 16 were criticality unacceptable. In particular, their analysis highlighted the impact of the drug dosage form, the lack of scientific information and the human factor on this preparation. Eleven action sheets have been written. DISCUSSION: The risk management requires significant human investment, material resources and organizational solutions: formations, information, i.e. computerized prescribing, dispensing and administering system, centralized drug preparations, automated drugs cabinets or unit drug daily dispensing system. CONCLUSION: Control these risks means to get specific actions at pediatric wards, enhance dispensing system by the hospital pharmacist and the support of the pharmaceutical industry to get commercially available pediatric drugs.

Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients.

Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there is a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myélome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for progression-free survival (PFS): 1p22: 19.8 months vs 33.6 months (P<0.001) and 1p32: 14.4 months vs 33.6 months (P<0.001); and overall survival (OS): 1p22: 44.2 months vs 96.8 months (P=0.002) and 1p32: 26.7 months vs 96.8 months (P<0.001). In multivariate analyses, 1p22 and 1p32 deletions still appear as independent negative prognostic factors for PFS and OS. In conclusion, our data show that 1p22 and 1p32 deletions are major negative prognostic factors for PFS and OS for patients with MM. We thus suggest that 1p32 deletion should be tested for all patients at diagnosis.

New insights into thyroglobulin pathophysiology revealed by the study of a family with congenital goiter.

CONTEXT: Thyroglobulin (TG) gene mutations cause congenital hypothyroidism (CH) with goiter. A founder effect has been proposed for some frequent mutations. Mutated proteins have a defect in intracellular transport causing intracellular retention with ultrastructural changes that resemble an endoplasmic reticulum storage disease. OBJECTIVE: To reveal new aspects of thyroglobulin pathophysiology through clinical, cellular, molecular, and genetic studies in a family presenting with CH due to TG mutations from Galicia, an iodine-deficient area of Spain. DESIGN: The included clinical evaluation of family members, DNA sequencing for TG gene mutation and haplotyping analysis, ultrastructural analysis of thyroid tissue specimens from affected subjects, analysis of effects of mutations found on TG gene transcription, and in vitro studies of cellular production and secretion of mutated proteins. SETTING: Locations included primary care and university hospitals. RESULTS: Family members with CH, mental retardation, and goiter were compound heterozygous for c.886C-->T (p.R277X) and g.IVS35+1delG. For c.886C-->T, a founder effect cannot be excluded, and its transcription was hardly detectable. g.IVS35+1delG caused an in-frame deletion in exon 35 and produced a protein that, although synthesized, could not be secreted. Ultrastructural analyses showed morphological changes consistent with an endoplasmic reticulum storage disease. CONCLUSION: The shorter thyroglobulin resulting from the novel g.IVS35+1delG was retained within the endoplasmic reticulum of thyrocytes, and together with p.R227X caused severe hypothyroidism with goiter. p.R277X, the most commonly described TG mutation, is caused by a TG exon-7 highly mutation-prone region, and the possibility that some cases were introduced to South America from Galicia cannot be excluded.

Factores moleculares pronósticos relacionados con el control del ciclo celular en el cáncer de mama. Situación actual / Molecular prognostic factors related to cell cycle in breast cancer. Current situation

El cáncer de mama es una de las enfermedades malignas más frecuentes en las mujeres. Su incidencia se ha ido incrementando cada año hasta considerarse un problema sanitario de características epidémicas. Alrededor de un 15% de las mujeres desarrolla cáncer de mama a lo largo de su vida. En los últimos años se ha realizado una gran cantidad de trabajos sobre los factores de riesgo y pronósticos de esta enfermedad. En esta revisión de la bibliografía científica, se presenta el estado actual de los factores pronósticos relacionados con la regulación del ciclo celular en el cáncer de mama (AU)

Breast cancer is one of the most common malignancies among women. The incidence of this disease has been increasing yearly and it could now be considered an epidemic disease. Approximately 15% of women will develop this kind cancer during their lifetime. In the last few years, multiple studies have been carried out on the risk and prognostic factors of breast cancer. We provide a review of the scientific literature on the current situation of molecular prognostic factors for breast cancer related to cell cycle control (AU)

[Drug interactions in an elderly population. Prospective assessment of their frequency and seriousness among 56 patients]. / Interactions médicamenteuses dans une population âgée.

OBJECTIVE: To assess the nature and the number of potential adverse drug interactions by analysis of outpatient prescriptions for elderly patients, of medications taken during the week before hospitalization in a general surgery department. METHOD: The study of 56 patients older than 65 years was conducted from November 2002 through February 2003. The outpatient prescriptions corresponding to medications taken during the 7 days before admission were analyzed by a pharmacy resident, who used data-processing tools and databases. RESULTS: Most patients (83%) knew the reason for their prescription. Thirteen (28%) reported using over-the-counter medication. Only 89% of the patients reported complete compliance with the prescription. The average age of the patients was 72.1 +/- 6.3 years and the median was 71 years [65-91]; 43% were women and 57% men. The 257 lines of prescriptions analyzed averaged 5.7 +/- 2.6 drugs (range: 2-10) per prescription. The average number of possible interactions was 3.1 +/- 2.8 per prescription for a total of 89 listed potential interactions. The levels observed were 3 warnings (3%), 37 precautions (42%) and 49 possible adverse interactions (55%). No contraindication was noted. The drugs mentioned most often were benzodiazepines, diuretics, conversion enzyme inhibitors, angiotensin II inhibitors, and beta-blockers. The potential risks most often found were hypotension, depression of the central nervous system, hypoglycemia and acute renal failure. The drug interactions were mainly due to the accumulation of the effects of separate drug classes. Deterioration in renal function was often noted as plasma concentration of the second drug increased. DISCUSSION: This exploratory study shows the reality of the iatrogenic risk for elderly patients. This analysis of outpatient prescriptions is consistent with findings in the literature. Analysis of interactions is conducted on a pairwise basis. It is thus difficult to envisage the consequences of the association of 5 or more drugs in patients with complex illnesses and diminished physiological and metabolic capacity. Patient files kept by the pharmacist could provide information about individual combinations ofthe prescription and over-the-counter drugs.

Stability of doxorubicin combined with Radioselectan, a contrast agent, for chemoembolization.

OBJECTIVE: To assess the stability of doxorubicin combined with Radioselectan. METHODS: Solutions of doxorubicin 5 mg/mL were prepared from commercially available 50 mg powder with 10 mL of Radioselectan. They were stored in glass syringes at 4, 25 and 45 degrees C. The concentrations of doxorubicin were determined using a stability-indicating high-performance liquid chromatography method. The initial and final pHs of solutions were compared. The times (t90) needed for doxorubicin to fall to 90% of its initial concentration were calculated by a linear regression analysis. RESULTS: The t90 [95% confidence limits] were 79 [75-83], 56 [53-59] and 22 [21-23] hours for the solutions stored at 4, 25 and 40 degrees C respectively. The initial pH of the solutions stored at 4, 25 and 40 degrees C were 6.52, 6.50 and 6.51 respectively. The final pH of solutions stored at 25 and 40 degrees C decreased significantly by 0.3 and 0.9 respectively. No change of pH solution stored at 4 degrees C was observed. CONCLUSION: Doxorubicin combined with Radioselectan stored at room temperature is stable for 48 h.

Mixed micelles of alkylamines and cetyltrimethylammonium chloride.

The influence of chain length and the nature of the head group on the composition of micelles of a binary mixture of cetyltrimethylammonium chloride with both unsubstituted and N-substituted n-octyl, n-decyl, and n-lauryl amines was established from the variation of the critical micelle concentration (cmc) as a function of the solution composition. A synergistic effect was observed in all instances that were found to be correlated with chain length and the type of N-substituent on the alkylamine head group. Experimental data were compared with theoretical predictions based on the equilibrium between micelles and monomers in solution. The Motomura treatment was used to determine the composition of each compound in the mixed micelles (Xi(m)). Mixing nonideality was expressed in terms of the molecular interaction parameter (beta12) as determined using the theory of Holland and Rubingh. Finally, the molecular thermodynamic model for mixed surfactant systems developed by Puvvada and Blankschtein was used to estimate the micellization free energy (DeltaGM) and to evaluate the synergistic phenomenon.

Bacterial contamination of enteral nutrition in a paediatric hospital.

A prospective study was performed in a paediatric hospital to evaluate the incidence of bacterial contamination in enteral nutrition bags and to determine the critical points of process. During two separate one-month periods, all children receiving pump-assisted enteral nutrition were enrolled in the study. Samples for microbiological analysis were collected from enteral nutrition bags after administration in the first and second study period (sample T(2)). In the second study period, two additional samples were made at the end of the feed preparation process. One was refrigerated immediately (sample T(0)) and the other was sealed in a tube that followed the enteral nutrition solution until the end of its administration (sample T(1)). Bacterial contamination was detectable above 10(2)cfu/mL. Twenty-six out of 40 patients were included in the first study period and 14 out of 44 in the second study period. Contamination (>10(2)cfu/mL) occurred in nine of 26 samples (35%) and seven of 14 samples (50%) in the first and second study periods, respectively. Of these, five (20%) and three (21%) contained significant contamination (>/=10(4)cfu/mL). Bacteria of low pathogenicity were found in T(0) samples. Bacteria present in T(2) samples were pathogenic and multiple in 50% of cases. These results suggest that manipulation of the enteral nutrition bags at the bedside is critical for bacterial safety.

[Drug administration to paediatric inpatient]. / L'administration des médicaments à l'enfant hospitalisé.

OBJECTIVE: Available commercial drugs in France are often unsuitable for children. The aim of this study was, for every medicinal form orally or parenterally administered, to identify and to quantify difficulties met by the nurses administering drugs to paediatric inpatients and to propose solutions to main identified problems. MATERIAL AND METHOD: The study was realized in 14 hospitals by direct observation. The observer, provided with a questionnaire, followed during a time slot of at least 2 h for one or several nurses and raised all the oral or injectable administrations. RESULTS: One thousand and nine hundred forty-six observations were performed. The children were 12.6 +/- 17 months old, and weighed 8.5 +/- 9.4 kg. Injectable drugs: half of the observations showed a posology and a mode of dilution not corresponding to the summary of product characteristics. Eight percent of orally administered drugs were injectable drugs. In 35.5% of cases, administered amount was lower than the quarter of the present quantity in the therapeutic unity. The rest of the therapeutic unity was thrown (77.2% of cases). Liquid oral forms: liquid oral forms were ready for use regarding 83.8% of cases. The medicine was readministered to the same patient (23.5%), and/or administered to other patients (80.0%). Capsules: 66.9% of the administered capsules were prepared by the hospital pharmacies. The pharmacies organized with an unit dose drug dispensing system produced significantly more preparations than those working by global distribution (P < 0.0001). In 58.4% of cases, the administered capsule was an off-label drug. Tablets: 46% of drug administration concerned a tablet without pediatric indication. 46.7% of tablets were cut, 74% were crushed. Bags: in 35.2% of observations, the bag was not administered in its entirety. CONCLUSION: Our study confirms the unsuitability of drugs to paediatric inpatients, the necessity of recommendations of good practices in the administration of drugs to paediatric inpatients, and proposes corrective actions.

Outbreak of Burkholderia cepacia bacteremia in a pediatric hospital due to contamination of lipid emulsion stoppers.

We describe a 7-month outbreak of nosocomial Burkholderia cepacia bacteremia involving eight children in a pediatric hospital and the results of epidemiological investigations. A B. cepacia strain genotypically identical to the blood isolates was recovered from the upper surface of capped rubber stoppers of bottles of a commercial lipid emulsion used for parenteral nutrition.

A nonparametric approach to calculate critical micelle concentrations: the local polynomial regression method.

The application of a statistical method, the local polynomial regression method, (LPRM), based on a nonparametric estimation of the regression function to determine the critical micelle concentration (cmc) is presented. The method is extremely flexible because it does not impose any parametric model on the subjacent structure of the data but rather allows the data to speak for themselves. Good concordance of cmc values with those obtained by other methods was found for systems in which the variation of a measured physical property with concentration showed an abrupt change. When this variation was slow, discrepancies between the values obtained by LPRM and others methods were found.

Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation.

Neurogenic inflammation is believed to originate with the antidromic release of substance P, and of other neurokinins encoded by the preprotachykinin A (PPT-A) gene, from unmyelinated nerve fibers (C-fibers) following noxious stimuli. Consistent with this concept, we show here that selective sensory-fiber denervation with capsaicin and targeted deletion of the PPT-A gene protect murine lungs against both immune complex-mediated and stretch-mediated injuries. Reconstitution of PPT-A gene-deleted mice with WT bone marrow does not abrogate this protection, demonstrating a critical role for PPT-A gene expression by sensory neurons in pulmonary inflammation. Surprisingly, reconstitution of WT mice with PPT-A gene-deficient bone marrow also confers protection against pulmonary injury, revealing that PPT-A gene expression in hemopoietic cells has a previously unanticipated essential role in tissue injury. Taken together, these findings demonstrate a critical synergy between capsaicin-sensitive sensory fibers and hemopoietic cells in neurokinin-mediated inflammation and suggest that such synergy may be the basis for a stereotypical mechanism of response to injury in the respiratory tract.

On lung nerves and neurogenic injury.

Information accumulated in recent years has begun to unveil a previously unsuspected complexity in the innervation of the lungs. We know now that the conducting airways receive a highly redundant supply of vagal motor and sensory fibers; that many of these fibers cross over from the contralateral side of the brain to reach distant portions of the lung, thereby assuring the symmetry and simultaneity of the bronchomotor responses; and that, perhaps in recognition of the different functions and properties of proximal and distal airways, vagal motor fibers have a distinctive segmental distribution. Both sensory and motor neurons serve as the input and output elements of a complex brain stem neuronal network, which integrates the regulation of airway smooth muscle tone into the control of ventilation. This network has a local counterpart in the airway walls, where a heterogeneous population of intrinsic neurons may act not only as a relay for cholinergic stimuli, but also as a local mechanism of inflammatory modulation. The interruption of the nerve supply to the lungs (for instance after lung transplantation) abolishes the integration of bronchomotor and ventilatory activities, and, by increasing airway deformation, may initiate fibroproliferative responses in the airway walls. In addition, the destruction of vagal motor and sensory fibers leaves behind a surviving population of denervated intrinsic neurons, which may act as a disregulated mechanism of inflammatory amplification.

The relationship between introduction of American society of clinical oncology guidelines and the use of colony-stimulating factors in clinical practice in a Paris university hospital.

BACKGROUND: Clinical practice guidelines are issued periodically by professional medical societies or committees to assist practitioners in clinical decision making. However, it is unclear whether such guidelines have any lasting impact on clinical practice. OBJECTIVE: The purpose of this study was to assess the impact of the American Society of Clinical Oncology (ASCO) guidelines regarding use of hematopoietic colony-stimulating factors (CSF) on cancer care in a university hospital in Paris. METHODS: The study was performed at Hjpital Tenon, an 830-bed university hospital in Paris, in 1996 and 1997, both before and after the ASCO guidelines were implemented. The guidelines were first disseminated as a continuing medical education program and then actively implemented using a CSF prescription order form summarizing the guidelines. This form had to be used during the patient consultation and was sent to the Hjpital Tenon pharmacy for CSF dispensation. Even if CSF use did not comply with the ASCO guidelines, the pharmacy filled the prescription. Seven other university hospitals in Paris, where the ASCO guidelines were not actively implemented, comprised the control group. The main outcome measure was the proportion of prescriptions in compliance with the 1996 update of the ASCO guidelines. Secondary outcome measures were the proportions of prescriptions in compliance with ASCO guidelines regarding primary prophylactic, secondary prophylactic, and therapeutic CSF administration. RESULTS: Before implementation of the ASCO guidelines, CSF use in compliance with the guidelines was 39% (41/105) at the study site and 31% (16/51) at the control sites (P > 0.05). Six months after dissemination and implementation of the guidelines, the proportion of CSF prescriptions complying with ASCO guidelines increased significantly versus baseline (P = 0.003) in the study group, to 61% (50/82). However, even after the guidelines were implemented, compliance with guidelines on primary prophylactic CSF administration did not change significantly versus before implementation in the study group (12% [5/41] before implementation vs 6% [2/33] after implementation; P > 0.05). CONCLUSIONS: The results suggest an association between the active implementation strategy (continuing medical education and CSF prescription reminder form) and physician compliance with the ASCO guidelines. Implementation of the ASCO guidelines appears to have had some impact on medical practice.

Labeling of vagal motoneurons and central afferents after injection of cholera toxin B into the airway lumen.

We tested the hypothesis that application of the subunit B of cholera toxin (CTB) to the airway mucosa would produce labeling of neuronal somata and sensory fibers in the medulla oblongata. Using (125)I-CTB as a tracer, we demonstrated first that CTB is transported across the tracheal epithelium, but once in the airway wall, it remains confined to the subepithelial space and lamina propria. Despite the rarity of intrinsic neurons in these areas, intraluminal CTB labeled approximately 10-60 neurons/rat in the nucleus ambiguus and a smaller number of neurons in the dorsal motor nucleus of the vagus. Well-defined sensory fiber terminals were also labeled in the commissural, medial, and ventrolateral subnuclei of the nucleus of the tractus solitarius. Approximately 50 and 90% of the neurons labeled by intraluminal CTB were also labeled by injections of FluoroGold into the tracheal adventitia and lung parenchyma, respectively. These findings demonstrate that a substantial number of medullary vagal motoneurons innervate targets in the vicinity of the airway epithelium. These neurons do not appear to be segregated anatomically from vagal motoneurons that project to deeper layers of the airway wall or lung parenchyma.