[Overnight extubation is not associated with extubation failure in pediatric intensive care unit patients: a retrospective cohort study]. / La extubación durante la noche no se asocia con su fracaso en pacientes pediátricos de Unidad de Cuidados Intensivos: Estudio de cohorte retrospectivo.

There is little known about the time of the day and the nature of it (business day/non-business day) at which extubation is performed, and whether it is safe during the night. OBJECTIVE: to describe the frequency of nocturnal extubation (NE) and non-business day extubation (nBDE). In addition, to determine the association between these and clinical outcomes. PATIENTS AND METHOD: Retrospective cohort study of patients under 18 years of age who received invasive mechanical ventilation (MV) and underwent an extubation attempt in a high complexity Pediatric Critical Patient Unit (PCPU) between 01/01/2018 to 12/31/2021. Primary exposure: NE, which was defined as that performed between 20:01 and 8:00 hours. Its association with extubation failure (EF), duration of invasive MV, and length of stay in the PCPU was evaluated. RESULTS: 146 patients were included [58.9% males, age 1.14 (0.25 - 5.5) years]. NE was performed in 17.8%. Nocturnal extubation was not associated with EF nor was the day of extubation. The EF was 3.8% in NE and 5% in daytime extubation (DE) (p = 0.80). Duration of invasive MV was shorter in NE than DE [48 (24-73.5) vs. 72 (48-96) h, p = 0.02]. CONCLUSIONS: NE was not associated with EF. Patients with NE had shorter duration of invasive MV, and the latter was associated with EF. Withdrawal of invasive MV should be considered at the first opportunity and be determined by clinical factors, rather than time of day.

Hand Hygiene Practices and Promotion in Public Hospitals in Western Sierra Leone: Changes Following Operational Research in 2021.

Hand hygiene is the most important intervention for preventing healthcare-associated infections and can reduce preventable morbidity and mortality. We described the changes in hand hygiene practices and promotion in 13 public hospitals (six secondary and seven tertiary) in the Western Area of Sierra Leone following the implementation of recommendations from an operational research study. This was a "before and after" observational study involving two routine cross-sectional assessments using the WHO hand hygiene self-assessment framework (HHSAF) tool. The overall mean HHSAF score changed from 273 in May 2021 to 278 in April 2023; it decreased from 278 to 250 for secondary hospitals but increased from 263 to 303 for tertiary hospitals. The overall mean HHSAF score and that of the tertiary hospitals remained at the "intermediate" level, while secondary hospitals declined from "intermediate" to "basic" level. The mean score increased for the "system change" and "institutional safety climate" domains, decreased for "training and education" and "reminders in the workplace" domains, and remained the same for the "evaluation and feedback" domain. Limited resources for hand hygiene promotion, lack of budgetary support, and formalized patient engagement programs are the persistent gaps that should be addressed to improve hand hygiene practices and promotion.

Improvement in Infection Prevention and Control Compliance at the Three Tertiary Hospitals of Sierra Leone following an Operational Research Study.

Implementing infection prevention and control (IPC) programmes in line with the World Health Organization's (WHO) eight core components has been challenging in Sierra Leone. In 2021, a baseline study found that IPC compliance in three tertiary hospitals was sub-optimal. We aimed to measure the change in IPC compliance and describe recommended actions at these hospitals in 2023. This was a 'before and after' observational study using two routine cross-sectional assessments of IPC compliance using the WHO IPC Assessment Framework tool. IPC compliance was graded as inadequate (0-200), basic (201-400), intermediate (401-600), and advanced (601-800). The overall compliance scores for each hospital showed an improvement from 'Basic' in 2021 to 'Intermediate' in 2023, with a percentage increase in scores of 16.9%, 18.7%, and 26.9% in these hospitals. There was improved compliance in all core components, with the majority in the 'Intermediate' level for each hospital IPC programme. Recommended actions including the training of healthcare workers and revision of IPC guidelines were undertaken, but a dedicated IPC budget and healthcare-associated infection surveillance remained as gaps in 2023. Operational research is valuable in monitoring and improving IPC programme implementation. To reach the 'Advanced' level, these hospitals should establish a dedicated IPC budget and develop long-term implementation plans.

Red cell pyruvate kinase deficiency in Southern Sardinia.

Pyruvate kinase (PK) deficiency is the most frequent red cell enzymatic defect responsible for hereditary non-spherocytic hemolytic anemia. The clinical picture is quite variable and the reasons of this variability have been only partially clarified. We report the clinical description and the extended molecular analysis in 3 PK deficient patients with clinical phenotype of variable severity. We studied the clinical and hematological aspects of 3 patients and analyzed the following genes: pyruvate kinase-R, glucose-6-phosphate-dehydrogenase, α-globin, uridindiphosphoglucuronil transferase and HFE. One patient (A) with a severe clinical picture resulted homozygote for exon 8 nt994A substitution, the other 2 (brothers) were compound heterozygotes for exon 8 nt994A and exon 11 nt1456T mutation. One of the two brothers with a more severe phenotype coinherited also had G6PD deficiency, while both had microcytosis due to the homozygosity for the non-deletional form of α-thalassemia ATG→ACG substitution at the initiation codon of the alpha2 globin gene. Our results suggest that extended molecular analysis is useful for studying how several interacting gene mutations contribute to the clinical variability of pyruvate kinase deficiency.

Posttranslational deamidation of proteins: the case of hemoglobin J Sardegna [alpha50(CD8)His-->Asn-->Asp].

Hemoglobin J Sardegna [alpha50(CD8)His-->Asn -->Asp] is a human Hb variant in which a posttranslational deamidation process takes place, transforming an Asn to an Asp residue. This variant, particularly widespread in northern Sardinia, has for the first time been characterized at the DNA level (codon 50 C-->A) on the selectively amplified alpha2-globin gene. We determined the protein and DNA sequences and performed cellulose acetate electrophoresis, isoelectric focusing, globin chain separation, stability tests with isopropanol and heat precipitation, and oxygen affinity analyses on whole blood to fully characterize the variant. A comprehensive review of the deamidation processes involving Asn and Gln residues in mutant proteins is reported, together with a discussion of the molecular mechanisms of such deamidations. Finally, examples of other proteins of clinical importance in which Asn or Gln residues have been implicated by DNA analysis alone are presented. These findings point out the importance of the complete characterization of variant proteins by use of both DNA and protein analyses.

Globin chain synthesis analysis by high performance liquid chromatography in the screening of thalassemia syndromes.

We applied reversed phase high performance liquid chromatography for globin chain synthesis analysis in screening for beta-thalassemia. The alpha/non-alpha-globin chain synthesis ratios have been determined in alpha-, beta-, and deltabeta-thalassemia carriers using the classical carboxymethyl cellulose chromatography as the reference method. Reversed phase high performance liquid chromatography is fast, accurate, and reproducible, and may be a suitable alternative for the traditional carboxymethyl cellulose chromatography.

Chronic ethanol intoxication enhances [3H]CCPA binding and does not reduce A1 adenosine receptor function in rat cerebellum.

The effects of acute and chronic treatment with ethanol on the function of A1 adenosine receptor in the rat cerebellar cortex were investigated. Acute administration of ethanol (0.5-5 g/kg) had no effect on the binding of the A1-receptor agonist [3H]2-chloro-N6-cyclopentyladenosine ([3H]CCPA) or that the antagonist [3H]8-cyclopentyl-1-3-dipropylxanthine ([3H]DPCPX) in rat cerebellar cortical membranes. Rats were rendered ethanol dependent by repeated forced oral administration of ethanol (12-18 g/kg per day) for 6 days. [3H]CCPA binding was increased by 23% in cerebellar cortical membranes prepared from rats killed 3 h after ethanol withdrawal compared with saline-treated animals. The increase in [3H]CCPA binding was still apparent 12-24 h after the last ethanol administration, but was no longer detectable 3-6 days after ethanol withdrawal. In contrast, the binding of [3H]DPCPX was not modified in the cerebellar cortex of rats killed at various times after ethanol withdrawal. The acute administration of CCPA [0.25-1 mg/kg, intraperitoneally (IP)] suppressed the tremors and audiogenic seizures apparent 24 h after ethanol withdrawal. Moreover, repeated coadministration of CCPA (0.5 mg/kg, IP, four times daily) and ethanol did not prevent the generation of audiogenic seizures during withdrawal but completely prevented mortality. Finally, CCPA antagonized with similar potencies and efficacies the isoniazid-induced convulsions observed in control and ethanol-withdrawn rats. These results indicate that long-term treatment with intoxicating doses of ethanol enhances [3H]CCPA binding but does not reduce the anticonvulsant efficacy of CCPA or the function of A1 adenosine receptors.

[Theophylline in childhood asthma. Pharmacokinetic and clinical study (author's transl)]. / La théophylline chez l'enfant asthmatique. Etude pharmacocinétique et clinique.

After an intra-venous injection of a single dose (4.24 +/- 0.94 mg/kg) of anhydrous theophylline in 20 children aged 4 to 16 years, the pharmacokinetic characteristics (mean and standard deviation) were as follow: half life (T 1/2 6.06 +/- 2.53; apparent distribution volume (Vd) 0.585 +/- 0.148 l/kg and clearance from the body (Cl) at 0.078 +/- 0.35 l/kg/w. The absorption of anhydrous theophylline syrup, given to 13 children during an exacerbation of their asthma, was consistent, quick and complete. Two hours after a dose of 6 mg/kg, the plasma levels were 11.39 +/- 2.04 mg/litre. On seven occasions, the clinical results were good. The absorption of the tablet form of anhydrous theophylline was more irregular. A prolonged course of treatment in 20 subjects aged 4.5 to 17.2 years confirmed the wide variety of doses required to maintain plasma theophylline levels in the 10 to 20 mg/litre range. The doses required varied from 10 to 22.5 mg/kg/day. The correlation between the actual and calculated needs on the basis of theophylline clearance was poor (due to the bioavailability of the drug and the close dependent character of the clearance). Seven times, the results were good (twice mean theophylline levels below 10 mg/litre). The proposition of good results in this study is less than that reported in the literature.