| 1. |
- Sandén, Anna Maria, et al.
(författare)
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Limiting factors in Escherichia coli fed-batch production of recombinant proteins
- 2003
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 81:2, s. 158-166
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Tidskriftsartikel (refereegranskat)abstract
- Fed-batch production of recombinant beta-galactosidase in E. coli was studied with respect to the specific growth rate at induction. The cultivations were designed to induce protein production by IPTG at a glucose feed rate corresponding to high (mu = 0.5 h(-1)) or low (mu = 0.1 h(-1)) specific growth rate. Protein production rate was approximately 100% higher at the higher specific growth rate, resulting in the accumulation of beta-galactosidase up to 30% of the total cell protein. Transcription analysis showed that beta-galactosidase-specific messenger RNA was immediately formed after induction (<5 min), but the amount was the same in both cases and was thus not the initial limiting factor. The content of ribosomes, as represented by rRNA, rapidly decreased with specific growth rate from a relative level of 100%, at the high specific growth rate, to 20% at the low specific growth rate. At high specific growth rate, ribosomes were additionally degraded upon induction due to the high production level. Translation therefore seemed to be the initial limiting factor of the protein synthesis capacity. The alarmone guanosine tetraphosphate increased at both high and low feed level inductions, indicating an induction-forced starvation of charged tRNA and/or glucose. The altered physiological status was also detected by the formation of acetic acid. However, the higher production rate resulted in high-level accumulation of acetic acid, which was absent at low feed rate production. Acetic acid production is thus coupled to the high product formation rate and is proposed to be due either to a precursor drain of Krebs cycle intermediates and a time lag before induction of the glyoxalate shunt, or to single amino acid overflow, since the model product is relatively poor in glycin and alanin. In conclusion, it is proposed that production at high specific growth rate becomes precursor-limited, while production at low specific growth rate is carbon- and/or energy-limited.
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| 2. |
- Andersson, Åsa C., et al.
(författare)
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Manipulated Oral and Rectal Drugs in a Paediatric Swedish University Hospital, a Registry-Based Study Comparing Two Study-Years, Ten Years Apart
- 2023
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- This is a registry-based study with the aim of describing and comparing the frequency of manipulations of solid oral and rectal medicines in 2009 and 2019 at inpatient units and an emergency department in a paediatric hospital within a Swedish university hospital. All patients aged 1 month-18 years with oral or rectal administrations were included. In total, 140,791 oral and rectal administrations were included in 2009, and 167,945 oral and rectal administrations were included in 2019. The frequency of patients receiving at least one manipulated oral medicine decreased between the study years, both in inpatient units and in the emergency department (from 19% to 17%, p = 0.0029 and from 11% to 5%, p < 0.0001, respectively). The frequency of patients receiving a manipulated rectal medicine also decreased between the study years, both in inpatient units and in the emergency department (from 22% to 10%, p < 0.0001 and from 35% to 7% 2019, p < 0.0001, respectively). The results show a decrease in the manipulation of both oral and rectal medicines to paediatric patients in 2019 compared to 2009. Even though this implies a safer practice, there is still a pronounced lack of child-friendly dosage forms and suitable strengths enabling the safe administration of medicines to sick children.
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| 3. |
- Andersson, Åsa C, et al.
(författare)
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'Working outside the box'-an interview study regarding manipulation of medicines with registered nurses and pharmacists at a Swedish paediatric hospital
- 2023
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 112:12, s. 2551-2559
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Studies on frequencies of manipulated medicines in paediatric care are common, but there is little knowledge of experiences of pharmacists and registered nurses in this area. The aim of this study was to explore registered nurses' and pharmacists' reasoning in the manipulation of medicines to paediatric inpatients.METHODS: Semistructured interviews with twelve registered nurses and seven pharmacists were performed at a Swedish paediatric university hospital. The interviews were transcribed verbatim and analysed using content analysis.RESULTS: Four major categories emerged from the analysis of the interviews: medicines management, knowledge, consulting others and organisation. Medicines management involved the process of drug handling, which is prescribing, reconstitution or manipulation and administration. Knowledge concerned both the knowledge base and how healthcare personnel seek information. Consulting others involved colleagues, registered nurses and pharmacists, between registered nurses, pharmacists and physicians and between registered nurses, pharmacists and caregivers. Organisation covered documentation, time and working environment.CONCLUSION: Both pharmacists and registered nurses stated that manipulation of medicines to paediatric patients was often necessary but felt unsafe due to lack of supporting guidelines. Pharmacists were natural members of the ward team, contributing with specific knowledge about medicines and formulations.
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| 4. |
- Dillner, Pernilla, et al.
(författare)
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Incidence and characteristics of adverse events in paediatric inpatient care : a systematic review and meta-analysis
- 2023
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Ingår i: BMJ Quality and Safety. - : BMJ. - 2044-5415 .- 2044-5423. ; :3, s. 133-149
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adverse events (AEs) cause suffering for hospitalised children, a fragile patient group where the delivery of adequate timely care is of great importance.OBJECTIVE: To report the incidence and characteristics of AEs, in paediatric inpatient care, as detected with the Global Trigger Tool (GTT), the Trigger Tool (TT) or the Harvard Medical Practice Study (HMPS) method.METHOD: MEDLINE, Embase, Web of Science and Google Scholar were searched from inception to June 2021, without language restrictions. Studies using manual record review were included if paediatric data were reported separately. We excluded studies reporting: AEs for a specific disease/diagnosis/treatment/procedure, or deceased patients; study protocols with no AE outcomes; conference abstracts, editorials and systematic reviews; clinical incident reports as the primary data source; and studies focusing on specific AEs only. Methodological risk of bias was assessed using a tool based on the Quality Assessment Tool for Diagnostic Accuracy Studies 2. Primary outcome was the percentage of admissions with ≥1 AEs. All statistical analyses were stratified by record review methodology (GTT/TT or HMPS) and by type of population. Meta-analyses, applying random-effects models, were carried out. The variability of the pooled estimates was characterised by 95% prediction intervals (PIs).RESULTS: We included 32 studies from 44 publications, conducted in 15 countries totalling 33 873 paediatric admissions. The total number of AEs identified was 8577. The most common types of AEs were nosocomial infections (range, 6.8%-59.6%) for the general care population and pulmonary-related (10.5%-36.7%) for intensive care. The reported incidence rates were highly heterogeneous. The PIs for the primary outcome were 3.8%-53.8% and 6.9%-91.6% for GTT/TT studies (general and intensive care population). The equivalent PI was 0.3%-33.7% for HMPS studies (general care). The PIs for preventable AEs were 7.4%-96.2% and 4.5%-98.9% for GTT/TT studies (general and intensive care population) and 10.4%-91.8% for HMPS studies (general care). The quality assessment indicated several methodological concerns regarding the included studies.CONCLUSION: The reported incidence of AEs is highly variable in paediatric inpatient care research, and it is not possible to estimate a reliable single rate. Poor reporting standards and methodological differences hinder the comparison of study results.
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