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1.
BMC Pediatr ; 24(1): 170, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459470

ABSTRACT

BACKGROUND: Mortality of children admitted to Intensive Care Units (ICU) is higher in low-to-middle-income countries (LMICs) as compared to high-income countries (HICs). There is paucity of information on outcomes following discharge from ICU, especially from sub-Saharan Africa region. This study was conducted to determine mortality and its associated factors among children admitted to Pediatric ICU (PICU) at Muhimbili National Hospital, from admission to three months after discharge. METHODOLOGY: This was a hospital-based prospective cohort study conducted between July 2021 and May 2022, among children admitted to PICU who were followed up for 3-month after discharge. Structured questionnaires were used to collect data from their medical charts. Telephone interviews were made after discharge. Medical records and verbal autopsy were used to determine the cause of death after discharge. Cox regression analysis was performed to assess the association between variables. A p-value of < 0.05 was considered statistically significant. Survival after PICU discharge was estimated by Kaplan - Meier curve. RESULTS: Of 323 children recruited, 177(54.8%) were male, with a median age of 17 months (1-168). The leading cause of PICU admission was severe sepsis 90/323(27.9%). A total of 161/323 children died, yielding an overall mortality of 49.8%. Of 173 children discharged from PICU, 33(19.1%) died. The leading cause of death among children who died in the general ward or as readmission into PICU was sepsis 4/17(23.5%). Respiratory diseases 4/16(25.0%) were the commonest cause of death among those who died after hospital discharge. Independent predictors of overall mortality included single organ dysfunction with hazard ratio(HR):5.97, 95% confidence interval (CI)(3.05-12.26)] and multiple organ dysfunction [HR:2.77,95%CI(1.03-2.21)]. Chronic illness[HR:8.13,95%CI(2.45-27.02)], thrombocytosis [HR:3.39,95%CI(1.32-8.73)], single[HR:3.57,95%CI(1.42-9.03)] and multiple organ dysfunction[HR:3.11,95%CI(1.01-9.61)] independently predicted post-PICU discharge mortality. CONCLUSION: Overall mortality and post- PICU discharge mortality were high and more likely to affect children with organ dysfunction, chronic illness, and thrombocytosis. The leading causes of mortality post- PICU discharge were sepsis and respiratory diseases. There is a need for a focused follow up plan of children post- PICU discharge, further research on the long term survival and strategies to improve it.


Subject(s)
Respiratory Tract Diseases , Sepsis , Thrombocytosis , Child , Humans , Male , Infant , Female , Patient Discharge , Multiple Organ Failure , Prospective Studies , Intensive Care Units, Pediatric , Hospitals , Chronic Disease , Retrospective Studies , Hospital Mortality
3.
Infect Drug Resist ; 17: 343-354, 2024.
Article in English | MEDLINE | ID: mdl-38312522

ABSTRACT

Purpose: To assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates of Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, ß-hemolytic streptococci, and coagulase-negative staphylococci (CoNS) from blood collected in Africa and Middle East (AfME), Asia Pacific (APAC), Europe, Latin America (LATAM), and North America from 2017 to 2020 as a part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Methods: Susceptibility and minimum inhibitory concentration were determined using broth microdilution for all antimicrobial agents by a central reference laboratory according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Results: Ceftaroline showed good activity (susceptibility ≥89.8%, MIC90 0.008-2 mg/L) against all Gram-positive isolates tested. All isolates of methicillin-susceptible S. aureus, penicillin-susceptible S. pneumoniae, S. agalactiae, S. dysgalactiae, and S. pyogenes were susceptible to ceftaroline (MIC90 0.008-0.25 mg/L). Ceftaroline susceptibility for MRSA isolates was 89.8% globally (MIC90 2 mg/L). Among the comparator agents, all isolates were susceptible to vancomycin, except S. epidermis (susceptibility, 99.9%). Among other agents, daptomycin, linezolid, and tigecycline showed potent activity (susceptibility ≥97.9%, MIC90 0.03-2 mg/L) against all isolates tested. Conclusion: Ceftaroline showed potent in vitro activity against global bloodstream isolates of Gram-positive bacteria collected between 2017 and 2020. Monitoring and surveillance of global as well as regional longitudinal trends of resistance rates among Gram-positive isolates causing bloodstream infections are important to limit the spread of AMR, establish stewardship measures, and manage and appropriately treat infections.

4.
Paediatr Anaesth ; 34(3): 225-234, 2024 03.
Article in English | MEDLINE | ID: mdl-37950428

ABSTRACT

BACKGROUND: Rapid-sequence tracheotomy and scalpel-bougie tracheotomy are two published approaches for establishing emergency front-of-neck access in infants. It is unknown whether there is a difference in performance times and success rates between the two approaches. AIMS: The aim of this cross-over randomized control trial study was to investigate whether the two approaches were equivalent for establishing tracheal access in rabbit cadavers. The underlying hypothesis was that the time to achieve the tracheal access is the same with both techniques. METHODS: Between May and September 2022, thirty physicians (pediatric anesthesiologists and intensivists) were randomized to perform front-of-neck access using one and then the other technique: rapid-sequence tracheotomy and scalpel-bougie tracheotomy. After watching training videos, each technique was practiced four times followed by a final tracheotomy during which study measurements were obtained. Based on existing data, an equivalence margin was set at ∆ = ±10 s for the duration of the procedure. The primary outcome was defined as the duration until tracheal tube placement was achieved successfully. Secondary outcomes included success rate, structural injuries, and subjective participant self-evaluation. RESULTS: The median duration of the scalpel-bougie tracheotomy was 48 s (95% CI: 37-57), while the duration of the rapid-sequence tracheotomy was 59 s (95% CI: 49-66, p = .07). The difference in the median duration between the two approaches was 11 s (95% CI: -4.9 to 29). The overall success rate was 93.3% (95% CI: 83.8%-98.2%). The scalpel-bougie tracheotomy resulted in significantly fewer damaged tracheal rings and was preferred among participants. CONCLUSIONS: The scalpel-bougie tracheotomy was slightly faster than the rapid-sequence tracheotomy and favored by participants, with fewer tracheal injuries. Therefore, we propose the scalpel-bougie tracheostomy as a rescue approach favoring the similarity to the adult approach for small children. The use of a comparable equipment kit for both children and adults facilitates standardization, performance, and logistics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05499273.


Subject(s)
Airway Management , Tracheostomy , Animals , Humans , Infant , Rabbits , Airway Management/methods , Intubation, Intratracheal/methods , Neck , Tracheostomy/methods , Tracheotomy/methods , Cross-Over Studies
5.
J Glob Antimicrob Resist ; 36: 123-131, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38154750

ABSTRACT

OBJECTIVES: Metallo-ß-lactamase (MBL)-producing Enterobacterales are a major challenge worldwide due to limited treatment options. Aztreonam-avibactam (ATM-AVI), which is under clinical development, has shown activity against MBL-positive isolates. This study evaluated the prevalence of MBL producers and the nature of enzymes among a global collection of clinical isolates of Enterobacterales from the Antimicrobial Testing Leadership and Surveillance program (ATLAS) surveillance program (2016-2020), and the antimicrobial activity of ATM-AVI and comparators against this collection. METHODS: Non-duplicate clinical isolates of Enterobacterales (N = 106 686) collected across 63 countries were analysed. Antimicrobial susceptibility was performed using broth microdilution. Minimum inhibitory concentrations (MICs) were interpreted using Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing breakpoints. Provisional pharmacokinetic/pharmacodynamic breakpoint of ≤8 mg/L was considered for ATM-AVI. ß-lactamase genes were characterized by polymerase chain reaction and sequencing. The Cochran Armitage Trend test was used to determine significant trends in percentage of isolates over time. RESULTS: Overall, MBL-positive isolates were 1.6% of total Enterobacterales isolates globally, with a significant increasing trend observed over time, globally and across regions (P < 0.05). New Delhi MBL (NDM) was the most common MBL (83.3%). ATM-AVI demonstrated potent activity against MBL-positive isolates (MIC ≤8 mg/L: 99.4% isolates inhibited; MIC90, 1 mg/L). Consistent activity was also noted across different regions. Potent activity was demonstrated against different NDM variants and MBL-positive isolates co-carrying other carbapenemases (98.1% and 99.7% isolates inhibited at ≤8 mg/L, respectively). About 0.6% MBL-positive isolates (10/1707) had MICs >8 mg/L for ATM-AVI. CONCLUSION: ATM-AVI demonstrated potent activity against MBL-positive isolates, including NDM variants and MBL-positive isolates co-carrying other carbapenemases, and may represent a good option for treating infections caused by MBL-positive Enterobacterales.


Subject(s)
Anti-Infective Agents , Ascomycota , Gammaproteobacteria , Aztreonam/pharmacology , beta-Lactamases/genetics , Azabicyclo Compounds/pharmacology
6.
Antibiotics (Basel) ; 12(11)2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37998793

ABSTRACT

Increasing antimicrobial resistance among multidrug-resistant (MDR), extended-spectrum ß-lactamase (ESBL)- and carbapenemase-producing Enterobacterales (CPE), in particular metallo-ß-lactamase (MBL)-positive strains, has led to limited treatment options in these isolates. This study evaluated the activity of aztreonam-avibactam (ATM-AVI) and comparator antimicrobials against Enterobacterales isolates and key resistance phenotypes stratified by wards, infection sources and geographic regions as part of the ATLAS program between 2016 and 2020. Minimum inhibitory concentrations (MICs) were determined per Clinical and Laboratory Standards Institute (CLSI) guidelines. The susceptibility of antimicrobials were interpreted using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A tentative pharmacokinetic/pharmacodynamic breakpoint of 8 µg/mL was considered for ATM-AVI activity. ATM-AVI inhibited ≥99.2% of Enterobacterales isolates across wards and ≥99.7% isolates across infection sources globally and in all regions at ≤8 µg/mL. For resistance phenotypes, ATM-AVI demonstrated sustained activity across wards and infection sources by inhibiting ≥98.5% and ≥99.1% of multidrug-resistant (MDR) isolates, ≥98.6% and ≥99.1% of ESBL-positive isolates, ≥96.8% and ≥90.9% of carbapenem-resistant (CR) isolates, and ≥96.8% and ≥97.4% of MBL-positive isolates, respectively, at ≤8 µg/mL globally and across regions. Overall, our study demonstrated that ATM-AVI represents an important therapeutic option for infections caused by Enterobacterales, including key resistance phenotypes across different wards and infection sources.

7.
GMS Ophthalmol Cases ; 13: Doc12, 2023.
Article in English | MEDLINE | ID: mdl-37575475

ABSTRACT

Background: While complex public health challenges and the emergence of variants have impeded responses to the COVID pandemic, vaccines continue to represent a crucial tool in mitigating the risk of morbidity and mortality. Safety issues weigh heavily upon both the utility and acceptability of every vaccine. Reports of sight-threatening events are scarce. Case description: We report the case of a hypertensive 45-year-old Filipino who noted unilateral (right eye) blurring of vision within 48 hours of his first dose of CoronaVac (Sinovac, China), an inactivated SARS-CoV-2/COVID-19 vaccine, with macular retinal arterial occlusion noted on day 21 post-inoculation. Further work-up revealed abnormal glycemic, metabolic, inflammatory, and bleeding parameters. Vision improved from counting fingers to 20/100 at week 6 with no interventions. Conclusion: A potential association between retinal vasoocclusion and inoculation with CoronaVac in our patient is supported by the temporal sequence of events, multiple mechanisms put forward in other cases, and reports of vascular adverse reactions in large country-level trials. It is mitigated by the profound infrequency of such events and the potentially substantial risk for ocular ischemic events imparted by the patient's baseline clinical background. Continued understanding of vaccine adverse reactions, however rare, is important not only for individual patient safety. This is helpful in ensuring the utility of current vaccines and in preserving the acceptability of vaccines through and beyond the current pandemic.

8.
Metab Brain Dis ; 38(6): 2115-2131, 2023 08.
Article in English | MEDLINE | ID: mdl-37204661

ABSTRACT

AIMS: This study aims to examine the associations between paraoxonase 1 (PON)1 status and acute ischemic stroke (AIS) and consequent disabilities. METHODS: This study recruited 122 patients with AIS and 40 healthy controls and assessed the Q192R gene variants, arylesterase (AREase) and chloromethyl phenylacetate (CMPAase) activities, and high-density lipoprotein cholesterol (HDLc) in baseline conditions. AREase and CMPAase were measured 3 months later. The National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin score (mRS) were assessed at baseline and 3 and 6 months later. RESULTS: Reduced CMPAase and increased AREase activities are significantly associated with AIS and mRS and NIHSS scores (baseline and 3 and 6 months later). The best predictor of AIS/disabilities was a decrease in the z-unit-based composite zCMPAase-zAREase score. Serum high density lipoprotein cholsterol (HDLc) was significantly correlated with CMPAase, but not AREase, activity and a lowered zCMPAase + zHDLc score was the second best predictor of AIS/disabilities. Regression analysis showed that 34.7% of the variance in baseline NIHSS was explained by zCMPAase-zAREase and zCMPAase + zHDLc composites, HDLc, and hypertension. Neural network analysis showed that stroke was differentiated from controls with an area under the ROC curve of 0.975 using both new composite scores, PON1 status, hypertension, dyslipidemia, previous stroke as body mass index. The PON1 Q192R genotype has many significant direct and mediated effects on AIS/disabilities, however, its overall effect was not significant. DISCUSSION: PON1 status and the CMPAase-HDLc complex play key roles in AIS and its disabilities at baseline and 3 and 6 months later.


Subject(s)
Brain Ischemia , Hypertension , Ischemic Stroke , Stroke , Humans , Aryldialkylphosphatase/genetics , Genotype
9.
Antioxidants (Basel) ; 12(1)2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36671047

ABSTRACT

In acute ischemic stroke (AIS), there are no data on whether oxidative stress biomarkers have effects above and beyond known risk factors and measurements of stroke volume. This study was conducted in 122 mild-moderate AIS patients and 40 controls and assessed the modified ranking scale (mRS) at baseline, and 3 and 6 months later. We measured lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products, paraoxonase 1 (PON1) activities and PON1 Q192R genotypes, high density lipoprotein cholesterol (HDL), sulfhydryl (-SH) groups), and diffusion-weighted imaging (DWI) stroke volume and fluid-attenuated inversion recovery (FLAIR) signal intensity. We found that (a) AIS is characterized by lower chloromethyl acetate CMPAase PON1 activity, HDL and -SH groups and increased LOOH and neurotoxicity (a composite of LOOH, inflammatory markers and glycated hemoglobin); (b) oxidative and antioxidant biomarkers strongly and independently predict mRS scores 3 and 6 months later, DWI stroke volume and FLAIR signal intensity; and (c) the PON1 Q192R variant has multiple effects on stroke outcomes that are mediated by its effects on antioxidant defenses and lipid peroxidation. Lipid peroxidation and lowered -SH and PON1-HDL activity are drug targets to prevent AIS and consequent neurodegenerative processes and increased oxidative reperfusion mediators due to ischemia-reperfusion injury.

10.
J Glob Antimicrob Resist ; 31: 239-247, 2022 12.
Article in English | MEDLINE | ID: mdl-36208850

ABSTRACT

OBJECTIVES: The objective of this study was to assess the in vitro activity of ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents against isolates of Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa collected in 2018 and 2019 by different centres worldwide from patients with respiratory tract infections. METHODS: Susceptibility and minimum inhibitory concentration (MIC) of all organisms were determined using broth microdilution methodology for CAZ-AVI, and a panel of comparator antimicrobial agents by a central reference laboratory according to Clinical and Laboratory Standards Institute guidelines and European Committee on Antimicrobial Susceptibility Testing guidelines. RESULTS: CAZ-AVI demonstrated potent antimicrobial activity against isolates of Enterobacter spp. (97.6% susceptibility, MIC90, 1 µg/ml), E. coli (98.5% susceptibility, MIC90, 0.25 µg/ml), K. pneumoniae (94.7% susceptibility, MIC90 2 µg/ml), and P. aeruginosa (91.2% susceptibility, MIC90 8 µg/ml). CAZ-AVI was also active (susceptibility >85%) against MDR isolates for all organisms except P. aeruginosa. Only a small proportion (<10%) of all isolates of Enterobacter spp. and E. coli were identified as XDR compared to isolates of K. pneumoniae and P. aeruginosa isolates (>20%). Susceptibility to CAZ-AVI was high (>70%) among XDR isolates of Enterobacter spp., K. pneumoniae, and E. coli, compared to P. aeruginosa (<70%). Among the comparator agents, only colistin showed consistent activity across all the organisms (>85%). CONCLUSION: Gram-negative respiratory isolates collected in 2018-2019 showed high susceptibility to CAZ-AVI; CAZ-AVI represents a potential treatment option against infection caused by these organisms.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Ceftazidime/pharmacology , Ceftazidime/therapeutic use , Azabicyclo Compounds/pharmacology , Azabicyclo Compounds/therapeutic use , Klebsiella pneumoniae , Pseudomonas aeruginosa
11.
Microb Drug Resist ; 28(11): 1019-1027, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36251881

ABSTRACT

This study assessed the in vitro antimicrobial activity of ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents, including aztreonam, cefepime, ceftazidime, meropenem, imipenem, colistin, piperacillin-tazobactam, and tigecycline against isolates of fluoroquinolone-resistant (FQ-R) Klebsiella pneumoniae collected in 2018 and 2019 from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Susceptibility and minimum inhibitory concentration were determined using broth microdilution for all antimicrobial agents by a central reference laboratory according to the Clinical and Laboratory Standards Institute guidelines and European Committee on Antimicrobial Susceptibility Testing guidelines. Of all the K. pneumoniae isolates (n = 10,906), 44.1% (4,814/10,906) were FQ-R. Of these, 71.3% (3,432/4,814) were extended-spectrum ß-lactamase (ESBL)-positive, and 10.4% (499/4,814) were CAZ-AVI-resistant. CAZ-AVI showed high susceptibility (>87%) against all the FQ-R K. pneumoniae isolates. However, metallo- ß-lactamase-positive isolates showed low susceptibility (3.8%; 18/470) to CAZ-AVI. Among the different geographical regions, CAZ-AVI showed the highest activity against isolates collected from North America (98.2%, 216/220) and lowest against those collected from Asia Pacific (APAC) (81.7%; 882/1,079). Among comparator agents, carbapenems showed a relatively lower susceptibility (<71.5%), while only tigecycline and colistin were active (>85%) across all isolates. In conclusion, CAZ-AVI may be a potential treatment option for FQ-R K. pneumoniae isolates. However, increasing CAZ-AVI resistance among ESBL-positive and metallo-ß-lactamase-positive isolates and in isolates from APAC warrants continuous surveillance.


Subject(s)
Ceftazidime , Klebsiella pneumoniae , Ceftazidime/pharmacology , Ceftazidime/therapeutic use , Anti-Bacterial Agents/pharmacology , Colistin/pharmacology , Tigecycline/pharmacology , Fluoroquinolones , Leadership , Azabicyclo Compounds/pharmacology , Drug Combinations , Microbial Sensitivity Tests , beta-Lactamases
12.
J Glob Antimicrob Resist ; 30: 214-221, 2022 09.
Article in English | MEDLINE | ID: mdl-35760303

ABSTRACT

OBJECTIVES: Infections caused by drug-resistant Enterobacterales including those producing metallo-ß-lactamases (MBLs) are particularly challenging due to limited therapeutic options. The drug combination aztreonam/avibactam (ATM-AVI) is under clinical development for treating serious infections caused by these strains. This study assessed the in vitro activity of ATM-AVI against Enterobacterales isolates collected globally in the ATLAS surveillance programme in 2019. METHODS: Clinical isolates of Enterobacterales (N = 18 713) including Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, and Serratia marcescens collected from 232 sites in 2019 were analysed. Antimicrobial susceptibility testing was performed by reference broth microdilution. A pharmacokinetic/pharmacodynamic based breakpoint of 8 mg/L was considered for ATM-AVI activity. RESULTS: ATM-AVI demonstrated potent antimicrobial activity against all Enterobacterales, with 99.9% isolates inhibited at MIC ≤8 mg/L (MIC90, 0.25 mg/L). MICs ≤8 mg/L (>99.0%) were noted for ATM-AVI across regions worldwide. Among other antimicrobials, amikacin, colistin, imipenem, meropenem, and tigecycline were also active (susceptibility >85.0%) against Enterobacterales. Activity of ATM-AVI was sustained against multidrug-resistant, extended-spectrum ß-lactamase producing, and carbapenem-resistant isolates (susceptibility >99%; MIC90, 0.25-0.5 mg/L). Importantly, potent activity for ATM-AVI (>99.0%; MIC90, 0.5 mg/L) was noted among MBL-positive isolates and those producing other carbapenemases, such as KPC and OXA-48. CONCLUSION: Our results demonstrated that ATM-AVI was highly active against a recent collection of Enterobacterales isolates, including those producing MBLs either alone or in combination with other carbapenemases. Thus, ATM-AVI represents a potential option for treating infections caused by antibiotic-resistant Enterobacterales including MBL-producing strains.


Subject(s)
Aztreonam , Ceftazidime , Azabicyclo Compounds/pharmacology , Aztreonam/pharmacology , Ceftazidime/pharmacology , Microbial Sensitivity Tests
13.
BMC Nurs ; 21(1): 55, 2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35255923

ABSTRACT

BACKGROUND: The clinical teaching is the core component of the nursing curriculum, the alarming pandemic rates brought uncertainty to clinical teaching, weighing the safety of patients, students, and faculty, which demanded essential modification in clinical teaching and resulted in challenges in relation to effective response to clinical teaching requirements. This study aimed to assess the effective clinical teaching from the nurse educators' perspective during the remote teaching that followed the COVID-19 pandemic. METHODS: This study is a national Web-based descriptive study. Participants were recruited from five major Nursing Colleges in Oman. Descriptive and inferential as well as multiple linear regression analyses were conducted. RESULTS: A total of 127 nurse educators completed the survey with mean age of 43.9 (SD = 6.9) years. The overall effective clinical teaching score was 54.4 (SD = 10.9) which is considered acceptable, although the nurse educators in Oman reported the highest score on the safety dimension of the effective clinical teaching. Furthermore, females, doctoral prepared nurse educators, and those who acted as preceptors reported higher effective clinical teaching levels compared to their counterparts. The regression analysis showed that age, gender, and attending infection control training are significant predictors of effective clinical teaching. CONCLUSION: The paradigm shift in clinical teaching requires adequate measures including identification and appropriate training of clinical instructors and preceptors to meet clinical teaching demands in remote teaching. It is also important to take actions that promote and maintain the safety prioritization in bedside clinical teaching. These measures might positively impact on the nursing education process.

14.
Neurobiol Dis ; 168: 105702, 2022 06 15.
Article in English | MEDLINE | ID: mdl-35339680

ABSTRACT

Human doublecortin (DCX) mutations are associated with severe brain malformations leading to aberrant neuron positioning (heterotopia), intellectual disability and epilepsy. DCX is a microtubule-associated protein which plays a key role during neurodevelopment in neuronal migration and differentiation. Dcx knockout (KO) mice show disorganized hippocampal pyramidal neurons. The CA2/CA3 pyramidal cell layer is present as two abnormal layers and disorganized CA3 KO pyramidal neurons are also more excitable than wild-type (WT) cells. To further identify abnormalities, we characterized Dcx KO hippocampal neurons at subcellular, molecular and ultrastructural levels. Severe defects were observed in mitochondria, affecting number and distribution. Also, the Golgi apparatus was visibly abnormal, increased in volume and abnormally organized. Transcriptome analyses from laser microdissected hippocampal tissue at postnatal day 60 (P60) highlighted organelle abnormalities. Ultrastructural studies of CA3 cells performed in P60 (young adult) and > 9 months (mature) tissue showed that organelle defects are persistent throughout life. Locomotor activity and fear memory of young and mature adults were also abnormal: Dcx KO mice consistently performed less well than WT littermates, with defects becoming more severe with age. Thus, we show that disruption of a neurodevelopmentally-regulated gene can lead to permanent organelle anomalies contributing to abnormal adult behavior.


Subject(s)
Doublecortin Protein/genetics , Neuropeptides , Animals , Doublecortin Domain Proteins , Golgi Apparatus , Hippocampus/metabolism , Mice , Mice, Knockout , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Mitochondria/metabolism , Mutation , Neuropeptides/genetics , Neuropeptides/metabolism , Pyramidal Cells/metabolism
15.
J Patient Saf ; 18(2): e573-e579, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34224500

ABSTRACT

OBJECTIVE: Effective communication minimizes medical errors and leads to improved team performance while treating critically ill patients. Closed-loop communication is routinely applied in high-risk industries but remains underutilized in healthcare. Simulation serves as an educational tool to introduce, practice, and appreciate the efficacy of closed-loop communication. METHODS: This observational before-and-after study investigates behavioral changes in communication among nurses brought on by simulation team training in a pediatric intensive care unit (PICU). The communication patterns of PICU nurses, who had no prior simulation experience, were observed during routine bedside care before and after undergoing in situ simulation.One month before and 1 and 3 months after simulation (intervention), 2 trained raters recorded nurse communications relative to callouts, uttered by the sender, and callbacks, reciprocated by the recipient. The impact of simulation on communication patterns was analyzed quantitatively. RESULTS: Among the 15 PICU nurses included in this study, significant changes in communication behavior were observed during patient care after communication-focused in situ simulation. The PICU nurses were significantly less likely to let a callout go unanswered during clinical routine. The effect prevailed both 1 month (P = 0.039) and 3 months (P = 0.033) after the educational exposure. CONCLUSIONS: This observational before-and-after study describes the prevalence and pattern of communication among PICU nurses during routine patient care and documents PICU nurses transferring simulation-acquired communication skills into their clinical environment after a single afternoon of in situ simulation. This successful transfer of simulation-acquired skills has the potential to improve patient safety and outcome.


Subject(s)
Intensive Care Units, Pediatric , Simulation Training , Child , Communication , Critical Illness , Humans , Patient Care
16.
Afr Health Sci ; 21(2): 817-825, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34795740

ABSTRACT

BACKGROUND: Injuries contribute to morbidity and mortality in children. This study was carried out to describe the pattern of childhood injuries and associated risk factors in Dar es Salaam, Tanzania. METHODS: This case control study was conducted in six selected health facilities in Dar es Salaam, Tanzania. Data were collected using a structured questionnaire. Cases and controls were children below 18 years who had suffered injuries and those without injury associated condition respectively. RESULTS: A total of 492 cases and 492 controls were included in the study, falls (32%), burns (26%), Road Traffic Injuries (14%) and cuts (10%) were the major types of injuries identified. Younger parents/guardians {Adjusted odds ratio (AOR)= 1.4; 95% CI: 1.4 -3.6}, more than six people in the same house (AOR= 1.8; 95% CI: 1.3-2.6), more than three children in the house {AOR= 1.4; 95% CI (1.0-2.0)}, absence of parent/guardian at time of injury occurrence (AOR= 1.6; 95% CI: 1.1-2.3), middle socio-economic (AOR=1.6; 95%CI: 1.1-2.4) and low socio-economic status (AOR= 1.5; 95% CI: 1.0-2.1) were independent risk factors for childhood injury. CONCLUSION: Falls, burns and road traffic injuries were the main injury types in this study. Inadequate supervision, overcrowding, lower socio-economic status and low maternal age were significant risk factors for childhood injuries.


Subject(s)
Accidental Injuries/epidemiology , Accidental Injuries/etiology , Case-Control Studies , Child, Preschool , Female , Humans , Male , Risk Factors , Surveys and Questionnaires , Tanzania/epidemiology
17.
J Antimicrob Chemother ; 76(11): 2833-2838, 2021 10 11.
Article in English | MEDLINE | ID: mdl-34436603

ABSTRACT

BACKGROUND: The combination aztreonam/avibactam is currently under Phase 3 trials for the treatment of serious infections caused by Gram-negative bacteria including those with MBLs. OBJECTIVES: To investigate the resistance mechanisms in Enterobacterales exhibiting aztreonam/avibactam MICs of ≥4 mg/L. METHODS: Among 8787 Enterobacterales, 17 (0.2%) isolates exhibited an aztreonam/avibactam MIC of ≥4 mg/L. Isolates were sequenced and screened for ß-lactamases. Sequences of porins, penicillin-binding protein 3 (PBP3) and expression levels of AmpC and AcrA were evaluated. RESULTS: Eleven (11/4154 isolates; 0.26%) Escherichia coli, three (3/1981; 0.15%) Klebsiella pneumoniae and three (3/628; 0.5%) Enterobacter cloacae were identified. All E. coli showed either an 'YRIK' or 'YRIN' insertion in PBP3. In general, these isolates carried blaCMY and/or blaCTX-M variants, except for one isolate from Korea that also produced NDM-5 and one isolate from Turkey that produced OXA-48. Two DHA-1-producing K. pneumoniae overexpressed acrA and had a premature stop codon in either OmpK35 or OmpK36, whereas a third K. pneumoniae carried blaPER-2 and had a premature stop codon in OmpK35. All three E. cloacae expressed AmpC at levels ≥570-fold, but sequence analysis did not reveal known amino acid alterations associated with decreased avibactam binding or increased hydrolysis of ß-lactams. Minor amino acid polymorphisms within OmpC, OmpF and PBP3 were noted among the E. cloacae. CONCLUSIONS: A small number of isolates (0.2%) met the inclusion criteria. E. coli showed altered PBP3 as the most relevant resistance mechanism, whereas K. pneumoniae had multiple resistance mechanisms. Further investigations are needed to clarify resistance in E. cloacae.


Subject(s)
Aztreonam , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds/pharmacology , Aztreonam/pharmacology , Ceftazidime , Drug Combinations , Escherichia coli/genetics , Klebsiella pneumoniae/genetics , Latin America , Microbial Sensitivity Tests , beta-Lactamases/genetics
18.
Proc Biol Sci ; 288(1957): 20211195, 2021 08 25.
Article in English | MEDLINE | ID: mdl-34428964

ABSTRACT

The prevalence of disease-driven mass mortality events is increasing, but our understanding of spatial variation in their magnitude, timing and triggers are often poorly resolved. Here, we use a novel range-wide dataset comprised 48 810 surveys to quantify how sea star wasting disease affected Pycnopodia helianthoides, the sunflower sea star, across its range from Baja California, Mexico to the Aleutian Islands, USA. We found that the outbreak occurred more rapidly, killed a greater percentage of the population and left fewer survivors in the southern half of the species's range. Pycnopodia now appears to be functionally extinct (greater than 99.2% declines) from Baja California, Mexico to Cape Flattery, Washington, USA and exhibited severe declines (greater than 87.8%) from the Salish Sea to the Gulf of Alaska. The importance of temperature in predicting Pycnopodia distribution rose more than fourfold after the outbreak, suggesting latitudinal variation in outbreak severity may stem from an interaction between disease severity and warmer waters. We found no evidence of population recovery in the years since the outbreak. Natural recovery in the southern half of the range is unlikely over the short term. Thus, assisted recovery will probably be required to restore the functional role of this predator on ecologically relevant time scales.


Subject(s)
Starfish , Wasting Syndrome , Alaska , Animals , Mexico/epidemiology , Temperature
19.
J Glob Antimicrob Resist ; 24: 316-320, 2021 03.
Article in English | MEDLINE | ID: mdl-33524556

ABSTRACT

OBJECTIVES: While aztreonam-avibactam is a potent ß-lactam-ß-lactamase-inhibitor combination, reduced in vitro activity against some Enterobacterales isolates has been reported. In this study, globally collected clinical isolates of Enterobacterales with elevated minimum inhibitory concentrations (MICs) for aztreonam-avibactam were examined for potential resistance mechanisms. METHODS: Isolates with aztreonam-avibactam MICs ≥8 µg/mL (n = 55: Escherichia coli, n = 38; Enterobacter cloacae, n = 10; Klebsiella pneumoniae, n = 3; others, n = 4) and <8 µg/mL (n = 18) collected for the INFORM global surveillance programme were characterized by short read whole-genome sequencing. Sequences were inspected for the presence of ß-lactamase genes, penicillin-binding protein (PBP) mutations, and disruptions in the coding sequences of porin genes. RESULTS: All isolates of E. coli testing with aztreonam-avibactam MIC values ≥8 µg/mL carried a previously documented four-amino-acid insertion in PBP3 at position 333 of YRI(K/N/P). Such mutations were absent in isolates with MICs <2 µg/mL (n = 6). Among other species, carriage of PER- or VEB-type ß-lactamases was identified in 10/17 (58.8%) of isolates testing with aztreonam-avibactam MICs ≥8 µg/mL, but no isolates with lower MIC values (n = 11). CONCLUSIONS: PBP3 mutations are known to confer resistance to aztreonam in E. coli, providing a rationale for the elevated MIC values for aztreonam-avibactam in these isolates. Elevated MICs in other isolates were associated with the carriage of PER-type ß-lactamases, which have been previously shown to be inhibited less effectively by avibactam than other Class A ß-lactamases and may contribute to this phenotype. Other resistance mechanisms contributing to poor in vitro activity for aztreonam-avibactam in some of these isolates are not yet elucidated.


Subject(s)
Aztreonam , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds/pharmacology , Aztreonam/pharmacology , Escherichia coli/genetics , Microbial Sensitivity Tests
20.
BMC Health Serv Res ; 21(1): 8, 2021 Jan 04.
Article in English | MEDLINE | ID: mdl-33397373

ABSTRACT

BACKGROUND: Patients' participation in decision making regarding their treatment is defined in ethical, legal and human rights standards in the provision of care that concerns health providers and the entire community. This study was conducted to document experiences of patients and health care providers on shared decision making. METHODS: This study employed a phenomenological study design using in-depth interview technique. Study participants were diabetic patients visiting the clinic and healthcare providers working at Muhimbili National Hospital. Data was collected using the semi-structured interview guide with open-ended questions using an audio digital recorder. Content analysis method was used during analysis whereby categories were reached through the process of coding assisted by Nvivo 12 software. RESULTS: Participants in this study expressed the role of shared decision-making in the care of patients with diabetes, with report of engagement of patients by health care providers in making treatment decisions. Participants reported no use of decision-making aids; however, health education tools were reported by participants to be used for educating patients. Limited time, patient beliefs and literacy were documented as barriers of effective engagement of patients in decision making by their healthcare providers. CONCLUSION: Engagement of patients in decision-making was noted in this study as experienced by participants of this study. Time, patient beliefs and patient literacy were documented as barriers for patients engagement, therefore diabetic clinic at Muhimbili National Hospital need to devise mechanisms for ensuring patients involvement in treatment decisions.


Subject(s)
Decision Making, Shared , Diabetes Mellitus , Decision Making , Diabetes Mellitus/therapy , Health Personnel , Humans , Patient Participation , Tanzania , Tertiary Care Centers
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