Evaluation of a Model of Long-Term Middle Ear Catheterization for Repeat Infusion Administration and Cochlear Hair Cell Injury in Guinea Pigs

2020 ◽  
Vol 48 (4) ◽  
pp. 586-592
Author(s):  
Jean-Francois Lafond ◽  
Kelly Tenneson ◽  
Frederick Émond ◽  
Claudia Foucault ◽  
Susan Vogel ◽  
...  
Keyword(s):  
Hair Cell ◽  
Middle Ear ◽  
Guinea Pigs ◽  
Animal Studies ◽  
Cell Injury ◽  
Response Assessment ◽  
Auditory Brain Stem Response ◽  
Membrane Rupture ◽  
Increased Risk

Middle ear administration has numerous applications, including antibiotherapy and gene therapy, and is increasingly used to target the auditory and vestibular systems. In animal studies, investigating repeated exposure that mimics clinical dosing regimens has remained a challenge due to the lack of suitable models. Intratympanic injections are not suitable for long-term studies due to the increased risk related to tympanic membrane rupture or scarring and repeat anesthesia events. Surgical models of middle ear catheterization previously used have not been reliable for longer than 4 weeks, resulted in elevated stress levels, and have been associated with significant changes related to the surgery and/or the presence of the catheter such as local trauma and inflammatory and degenerative processes. These complications cause decreased hearing/deafness and greatly diminish the value and accuracy of ototoxicity studies. We describe here a procedure that permits repeat dosing into the middle ear of guinea pigs and can be used to produce a model of aminoglycoside-induced hair cell injury. The innocuity of the procedures and the efficacy of the ototoxicity model were confirmed using auditory brain stem response assessment, histopathological evaluation, and cytocochleograms. Procedure-related changes were limited to minimal inflammation in the middle ear.

Neurodevelopmental Assessment in Kindergarten in Children Exposed to General Anesthesia before the Age of 4 Years

2016 ◽  
Vol 125 (4) ◽  
pp. 667-677 ◽  
Author(s):  
M. Ruth Graham ◽  
Marni Brownell ◽  
Daniel G. Chateau ◽  
Roxana D. Dragan ◽  
Charles Burchill ◽  
...  
Keyword(s):  
Animal Studies ◽  
General Anesthetic ◽  
Mixed Effect ◽  
Logistic Regression Models ◽  
Multiple Exposures ◽  
Increased Risk ◽  
Independent Association ◽  
Developmental Domains ◽  
Single Versus

Abstract Background Animal studies demonstrate general anesthetic (GA) toxicity in the developing brain. Clinical reports raise concern, but the risk of GA exposure to neurodevelopment in children remains uncertain. Methods The authors undertook a retrospective matched cohort study comparing children less than 4 yr of age exposed to GA to those with no GA exposure. The authors used the Early Development Instrument (EDI), a 104-component questionnaire, encompassing five developmental domains, completed in kindergarten as the outcome measure. Mixed-effect logistic regression models generated EDI estimates for single versus multiple GA exposure and compared both single and multiple exposures by the age of 0 to 2 or 2 to 4 yr. Known sociodemographic and physical confounders were incorporated as covariates in the models. Results A total of 18,056 children were studied: 3,850 exposed to a single GA and 620 exposed to two or more GA, who were matched to 13,586 nonexposed children. In children less than 2 yr of age, there was no independent association between single or multiple GA exposure and EDI results. Paradoxically, single exposure between 2 and 4 yr of age was associated with deficits, most significant for communication/general knowledge (estimate, −0.7; 95% CI, −0.93 to −0.47; P < 0.0001) and language/cognition (estimate, −0.34; 95% CI, −0.52 to −0.16; P < 0.0001) domains. Multiple GA exposure at the age of 2 to 4 yr did not confer greater risk than single GA exposure. Conclusions These findings refute the assumption that the earlier the GA exposure in children, the greater the likelihood of long-term neurocognitive risk. The authors cannot confirm an association between multiple GA exposure and increased risk of neurocognitive impairment, increasing the probability of confounding to explain the results.

Maternal Hypothyroidism during Pregnancy and the Risk for Infectious Morbidity of the Offspring

2019 ◽  
Vol 37 (03) ◽  
pp. 291-295 ◽  
Author(s):  
Ofer Beharier ◽  
Asnat Walfisch ◽  
Tamar Wainstock ◽  
Irit Szaingurten-Solodkin ◽  
Daniela Landau ◽  
...  
Keyword(s):  
Animal Studies ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Infectious Morbidity ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Increased Risk

Abstract Objective Animal studies indicate a possible intrauterine immunological imprinting in pregnancies complicated by hypothyroidism. We aimed to evaluate whether exposure to maternal hypothyroidism during pregnancy increases the risk of long-term infectious morbidity of the offspring. Study Design A retrospective cohort study compared the long-term risk of hospitalization associated with infectious morbidity in children exposed and unexposed in utero to maternal hypothyroidism. Outcome measures included infectious diagnoses obtained during any hospitalization of the offspring (up to the age of 18 years). Results The study included 224,950 deliveries. Of them, 1.1% (n = 2,481) were diagnosed with maternal hypothyroidism. Children exposed to maternal hypothyroidism had a significantly higher rate of hospitalizations related to infectious morbidity (13.2 vs. 11.2% for control; odds ratio: 1.2; 95% confidence interval: 1.08–1.36; p = 0.002). Specifically, incidences of ear, nose, and throat; respiratory; and ophthalmic infections were significantly higher among the exposed group. The Kaplan–Meier curve indicated that children exposed to maternal hypothyroidism had higher cumulative rates of long-term infectious morbidity. In the Cox proportional hazards model, maternal hypothyroidism remained independently associated with an increased risk of infectious morbidity in the offspring while adjusting for confounders. Conclusion Maternal hypothyroidism during pregnancy is associated with significant pediatric infectious morbidity of the offspring.

scholarly journals Febrile Seizures: Current Views and Investigations

2009 ◽  
Vol 36 (6) ◽  
pp. 679-686 ◽  
Author(s):  
Aylin Y. Reid ◽  
Michael A. Galic ◽  
G. Campbell Teskey ◽  
Quentin J. Pittman
Keyword(s):  
Animal Models ◽  
Current Literature ◽  
Growth And Development ◽  
Animal Studies ◽  
Pediatric Population ◽  
Febrile Seizures ◽  
Long Term Effects ◽  
Common Cause ◽  
Increased Risk

Febrile seizures (FSs) are seizures that occur during fever, usually at the time of a cold or flu, and represent the most common cause of seizures in the pediatric population. Up to 5% of children between the ages of six months and five years-of-age will experience a FS. Clinically these seizures are categorized as benign events with little impact on the growth and development of the child. However, studies have linked the occurrence of FSs to an increased risk of developing adult epileptic disorders. There are many unanswered questions about FSs, such as the mechanism of their generation, the long-term effects of these seizures, and their role in epileptogenesis. Answers are beginning to emerge based on results from animal studies. This review summarizes the current literature on animal models of FSs, mechanisms underlying the seizures, and functional, structural, and molecular changes that may result from them.

scholarly journals Clinical Evidence for Any Effect of Anesthesia on the Developing Brain

2018 ◽  
Vol 128 (4) ◽  
pp. 840-853 ◽  
Author(s):  
Andrew J. Davidson ◽  
Lena S. Sun
Keyword(s):  
Animal Studies ◽  
Large Population ◽  
Population Based ◽  
Human Studies ◽  
General Anesthetics ◽  
Multiple Exposures ◽  
Weak Evidence ◽  
Increased Risk ◽  
Different Populations

Abstract A recent U.S. Food and Drug Administration warning advised that prolonged or repeated exposure to general anesthetics may affect neurodevelopment in children. This warning is based on a wealth of preclinical animal studies and relatively few human studies. The human studies include a variety of different populations with several different outcome measures. Interpreting the results requires consideration of the outcome used, the power of the study, the length of exposure and the efforts to reduce the confounding effects of comorbidity and surgery. Most, but not all, of the large population-based studies find evidence for associations between surgery in early childhood and slightly worse subsequent academic achievement or increased risk for later diagnosis of a behavioral disability. In several studies, the amount of added risk is very small; however, there is some evidence for a greater association with multiple exposures. These results may be consistent with the preclinical data, but the possibility of confounding means the positive associations can only be regarded as weak evidence for causation. Finally, there is strong evidence that brief exposure is not associated with any long term risk in humans.

Long-Term Unemployment in Poland in 2008-2012 - Tendencies, Structure and Selected Determinants

2013 ◽  
Vol 8 (4) ◽  
pp. 347-359
Author(s):  
Leszek Kucharski
Keyword(s):  
Secondary Education ◽  
Young People ◽  
Level Of Education ◽  
Low Level ◽  
Increased Risk

This study presents the structure and tendencies in long-term unemployment in Poland in the years 2008-2012. This study identifies the groups of people with an increased risk of long-term unemployment. The analyses produced the following conclusions. The groups with the highest risk of long-term unemployment include: singles, people aged of 55 and above and people with a low level of education. Young people with university and general secondary education faced the lowest risk of long-term unemployment. 

scholarly journals Occasional and persistent frequent attenders and sickness absences in occupational health primary care: a longitudinal study in Finland

BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e024980 ◽  
Author(s):  
Tiia T M Reho ◽  
Salla A Atkins ◽  
Nina Talola ◽  
Markku P T Sumanen ◽  
Mervi Viljamaa ◽  
...  
Keyword(s):  
Primary Care ◽  
Longitudinal Study ◽  
Occupational Health ◽  
Sick Leave ◽  
Diagnostic Codes ◽  
Frequent Attenders ◽  
Frequent Attendance ◽  
Increased Risk ◽  
Working Age

ObjectivesFrequent attenders (FAs) create a substantial portion of primary care workload but little is known about FAs’ sickness absences. The aim of the study is to investigate how occasional and persistent frequent attendance is associated with sickness absences among the working population in occupational health (OH) primary care.Setting and participantsThis is a longitudinal study using medical record data (2014–2016) from an OH care provider in Finland. In total, 59 676 patients were included and categorised into occasional and persistent FAs or non-FAs. Sick-leave episodes and their lengths were collected along with associated diagnostic codes. Logistic regression was used to analyse associations between FA status and sick leaves of different lengths (1–3, 4–14 and ≥15 days).ResultsBoth occasional and persistent FA had more and longer duration of sick leave than non-FA through the study years. Persistent FAs had consistently high absence rates. Occasional FAs had elevated absence rates even 2 years after their frequent attendance period. Persistent FAs (OR=11 95% CI 7.54 to 16.06 in 2016) and occasional FAs (OR=2.95 95% CI 2.50 to 3.49 in 2016) were associated with long (≥15 days) sickness absence when compared with non-FAs. Both groups of FAs had an increased risk of long-term sick leaves indicating a risk of disability pension.ConclusionBoth occasional and persistent FAs should be identified in primary care units caring for working-age patients. As frequent attendance is associated with long sickness absences and possibly disability pensions, rehabilitation should be directed at this group to prevent work disability.

Epidemiological Evidence that Maternal Influenza Contributes to the Aetiology of Schizophrenia

1993 ◽  
Vol 163 (4) ◽  
pp. 522-534 ◽  
Author(s):  
W. Adams ◽  
R. E. Kendell ◽  
E. H. Hare ◽  
P. Munk-Jørgensen
Keyword(s):  
Data Sets ◽  
Time Lags ◽  
Epidemiological Evidence ◽  
Intrauterine Development ◽  
Increased Risk ◽  
Schizophrenic Patients ◽  
The Relationship ◽  
Monthly Incidence ◽  
Maternal Influenza

The epidemiological evidence that the offspring of women exposed to influenza in pregnancy are at increased risk of schizophrenia is conflicting. In an attempt to clarify the issue we explored the relationship between the monthly incidence of influenza (and measles) in the general population and the distribution of birth dates of three large series of schizophrenic patients - 16 960 Scottish patients born in 1932–60; 22 021 English patients born in 1921–60; and 18 723 Danish patients born in 1911–65. Exposure to the 1957 epidemic of A2 influenza in midpregnancy was associated with an increased incidence of schizophrenia, at least in females, in all three data sets. We also confirmed the previous report of a statistically significant long-term relationship between patients' birth dates and outbreaks of influenza in the English series, with time lags of - 2 and - 3 months (the sixth and seventh months of pregnancy). Despite several other negative studies by ourselves and others we conclude that these relationships are probably both genuine and causal; and that maternal influenza during the middle third of intrauterine development, or something closely associated with it, is implicated in the aetiology of some cases of schizophrenia.

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