Pediatric cochlear implantation: Early surgical intervention and parental quality of life.

OBJECTIVES: Pediatric cochlear implantation (CI) provides sound perception to children with significant sensorineural hearing loss and, despite its challenging process, early implantation can enhance children's speech/language outcomes and potentially improve parental quality of life (PQoL). This study aims to examine parental perspectives on quality of life and parenting children with CI. METHODS: This study combined retrospective chart review and parent reported outcomes. Data were abstracted from medical charts of 85 children who underwent CI between 2016 and 2022 at a tertiary pediatric hospital. Parents were administered the Acceptance and Action Questionnaire (AAQ-MCHL), an 8-item self-report assessment of quality of life for parents of children with CI. Multivariate linear regression analyses examined clinical factors associated with PQoL scores. RESULTS: Parents whose children were implanted at less than two years of age reported significantly higher PQoL, indicated by lower AAQ scores, with a mean AAQ-MCHL of 7.6 + 5.7. In contrast, implantation at age >2 years yielded a mean AAQ-MCHL of 16.2 + 9.6. Parents interviewed within one year post-surgery reported lower PQoL, with a mean AAQ-MCHL of 12.3 + 8.8 compared to those interviewed after one year, with 20.5 + 10.4. CONCLUSION: Early identification of profound hearing loss in children, coupled with early surgical CI, may be associated with higher parental quality of life. The beneficial outcomes appear to be potentiated over time. Further research is essential to fully comprehend the impact of CI on the quality of life of children and their parents.

Ensuring tympanostomy tube follow-up during the COVID-19 pandemic.

OBJECTIVES: The impact of the COVID-19 pandemic on surgical practice was widespread. Local health restrictions in many communities limited the number and types of patients seen and treated. Our goal is to understand the discrepancies in follow-up for bilateral myringotomy with tubes (BMT) and understand whether the pandemic made it more difficult for certain patient populations to continue routine follow up. METHODS: This cross-sectional study abstracted demographic and clinical data from the medical charts of randomized pediatric patients who underwent a BMT procedure between 2017 and 2022 at a tertiary pediatric academic care center site. Suboptimal follow-up was defined as no clinic visits within the first 6 months of surgery, and less than 3 follow-ups within a 24-month period after surgery. Data regarding secondary surgeries, clinical variables, race, zip code, and dates and number follow-ups were recorded from randomly chosen eligible charts. Complications were defined as need for revision surgery or development of post-tympanostomy sequalae such as perforation, cholesteatoma, or granuloma. RESULTS: Pre-pandemic (N = 150) patients from 2017 to 2019 and post-pandemic (N = 150) patients from 2020 to 2022 cohorts were analyzed. No significant differences were identified between the groups regarding age, presence of combined surgery, anesthesia class, diagnosis, or race. There was no significant difference in rate of complications or need for revision surgery between either cohort nor when stratified for demographics. CONCLUSION: Limitations imposed upon medical care including outpatient clinics due COVID restrictions did not have an impact on tympanostomy tube follow-up regarding frequency of visits and risk of complication or revision surgery. LEVEL OF EVIDENCE: IV.

Underinsurance in children is associated with worsened quality of life after cochlear implantation.

IMPORTANCE: Research has suggested that early cochlear implantation is associated with improved language outcomes. Select studies demonstrate that this translates into a higher quality of life following implantation. Previous work from our group has shown that underinsurance represents a risk factor for worsened auditory and language outcomes for implantees. However, to our knowledge, the effect of insurance status on quality of life outcomes following cochlear implantation has not been evaluated. OBJECTIVE: To assess quality of life outcomes for children receiving cochlear implants, accounting for age at implantation, insurance status, gender, surgeon, number of implants and duration of follow-up since implantation. DESIGN: A retrospective study using the Glasgow Children's Benefit Inventory (GCBI), a validated questionnaire measuring quality of life across four domains: learning, emotion, vitality and physical heath. Multivariate linear regression was used to examine the effects of age at implantation, insurance status, number of implants, sex, surgeon, and duration of follow-up on GCBI scores. Age at implantation was assessed as both a continuous and dichotomous variable, comparing children implanted by 12 months of age with those implanted after 12 months. SETTING: Children's National Health System in Washington, DC, a tertiary academic referral center. PARTICIPANTS: The GCBI was administered telephonically to parents/guardians of prelingually deaf children aged 2-16 years who received cochlear implants at the center between January 1, 2008 and December 31, 2018. RESULTS: Of 169 prelingually deafened implantee children who met inclusion criteria, parents/guardians of 64 (37.9%) responded to the questionnaire. After excluding children with late implantation (≥7 years age at CI) and missing GCBI responses, the final analytic sample consisted of 57 children. The mean age (SD) of the children at the time of the study was 3.3 (1.9) years, 63.2% were publicly insured, and 73.7% were implanted after 12 months of age. Average duration of follow-up was 3.9 (2.8) years. On a scale of -100 to +100, GCBI scores ranged from 41.7 to 95.8 (mean (SD), 64.0 (10.3)). Public health insurance (ß, -5.8 [95% CI, -10.6 to -0.01]), and older age at the time of implantation (ß, -0.1 [95% CI, -0.3 to 0.0]), particularly implantation following 12 months of age (p < 0.05), were significantly associated with lower GCBI scores after implantation. CONCLUSION: Publicly insured recipients of cochlear implants and children implanted at an older age, particularly after 12 months of age, experienced significantly lower quality of life measures.

Retained Tympanostomy Tubes: Who, What, When, Why, and How to Treat?

BACKGROUND: Tympanostomy tube placement is one of the most common surgical procedures performed across the globe. Controversies exist regarding what to do when a tube is considered to be retained in the tympanic membrane for too long. MATERIALS AND METHODS: Review of the PubMed medical literature starting in 1990, focusing on English language studies reporting on the definition, complications, and management of retained tympanostomy tubes. RESULTS: The medical literature reporting on outcomes regarding retained tympanostomy tubes is relatively sparse. Most studies recommend prophylactic removal of tubes after a defined period of time, usually around 2 to 3 years after placement. A preferred method of myringoplasty after tympanostomy tube retrieval has not been established, but most studies recommend grafting the perforation at the time of tube removal. CONCLUSIONS: Although a consensus as to the optimal management of retained tympanostomy tubes is not yet established in the medical literature, a preponderance of studies recommend prophylactic removal at defined period of time (>2-3 years) before the onset of complications such as otorrhea and granulation tissue formation. Due to a lack of best evidence, the surgeon's preference remains the guiding principle as to the best technique for myringoplasty at the time of removal.

Pharmacokinetics of THC in brain and testis, male gametotoxicity and premature apoptosis of spermatozoa.

An earlier report described the pharmacokinetics of delta-9 THC and the resulting brain function responses. In the present studies the pharmacokinetics of THC in plasma, brain and testis were related to impairment of spermatogenesis. THC- containing preparations, whatever their route of administration, were associated with the induction of gametotoxicity in all species studied including man. The pharmacokinetics and molecular binding of THC is similar in all experimental models. Concentrations of THC in plasma, fat, testis, brain and spleen were measured following administration of tracer amounts of C(14) delta-8 THC labelled at the C(11) position. Rats were administered 2 microCi of the tracer by i.m. injection, and killed at regular intervals after a single or multiple dose of the label. After a single dose, the maximal radioactivity was reached in brain after 2 and 4 h and amounted to 0.06% of the administered dose. In the testis, the concentration did not exceed 0.023% of the administered dose. In epididymal fat, the total radioactivity after 4 h was five times higher than in the brain and after 24 h it was eight times greater. After multiple injections of C(14) THC, concentrations of the drug remained low in the plasma, brain and testis not exceeding 2-7 ng/g, but the epididymal fat tracer concentration was 40-80 times higher. Plasma concentrations of C(14) THC were of the same magnitude as those measured by GCMS in the plasma of men exposed to marihuana smoke or THC, and in whom alterations of spermatogenesis were observed. In these studies, plasma THC ranged from 9.5x10(12) M to 2.4x10(14) M. These data illustrate the efficiency of the blood-brain barrier and blood-testicular barrier in limiting the storage of THC into brain and testis. During chronic exposure to THC the pharmacokinetic molecular mechanisms which limit the storage of THC in the brain and testis are not sufficient to prevent a persistent deregulation of membrane signalling and the induction of functional and morphological changes which reflect a premature apoptosis of spermatogenic cells. Long term, longitudinal epidemiological studies have reported decreased spermatogenesis in healthy, fertile adult males. But no study has been initiated to relate the oligospermia of this population to the consumption of widely used psychoactive drugs.

A molecular basis of the therapeutic and psychoactive properties of cannabis (delta9-tetrahydrocannabinol).

All of the therapeutic properties of marihuana (analgesic, antiemetic, appetite stimulant, antiglaucoma) have been duplicated by the tetrahydrocannabinol (THC) molecule or its synthetic derivatives. Today, the molecular mechanisms of action of these compounds have led to a general understanding of the pharmacological effects of marihuana and of its therapeutic properties. These mechanisms involve the specific binding of THC to the 7-transmembrane (7TM) domain G protein-linked receptor, a molecular switch which regulates signal transduction in the cell membrane. The natural ligand of the 7TM receptor is an eicosanoid, arachidonylethanolamide (AEA), generated in the membrane and derived from arachidonic acid. THC acts as a substitute ligand to the 7TM receptor site of AEA. THC would deregulate the physiological function of the 7TM receptor and of its ligand AEA. As a result, the therapeutic effects of the drug may not be separated from its adverse psychoactive and cardiovascular effects. The binding of THC to the 7TM receptor site of AEA induces allosteric changes in the receptor sites of neurotransmitter and opiates resulting in variable interactions and pharmacological responses. The pharmacokinetics of THC with its prolonged storage in fat and its slow release result in variable and delayed pharmacological response, which precludes precise dosing to achieve timely therapeutic effects. The experimental use of THC and of its synthetic analogues, agonists, and antagonists has provided novel information in the nature of molecular signaling in the cell membrane. As a result, the relationships between allosteric receptor responsiveness, molecular configuration of proteins, and physiological regulation of cellular and organ function may be further investigated.

The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking.

A pleasant sensory perception (PSP), the high of THC or of marihuana consumption, is a consistent functional response to this drug only manifested by man, and which occurs concurrently with an increased heart rate. However, it has not been possible to relate consistently magnitude and duration of these functional markers to THC plasma concentration, whatever the route of administration. A re-analysis of all the available clinical and experimental data reporting the pharmacokinetics and storage of THC in tissues in function of time, have indicated that the discrepancies between functional responses and plasma molecular THC concentration may be accounted for by the pharmacokinetics of THC. The instant uptake and unlimited storage of THC by neutral fat limits the molecular concentration of the drug present in the plasma to a level which does not exceed 6 x 10(14) molecules/ml. The physicochemical nature of the membrane lipid bilayer (of the blood-brain barrier) will restrict the access of THC into the bilayer receptors and its: reactive enzymes. The PSP and increased heart rate of marihuana is correlated with the molecular concentration of THC in the bilayer (blood-brain barrier) of the order of 10(12)-10(14) molecules/ml. This number in turn would be related to the number of functional THC receptor sites in the lipid bilayer. THC would exert its functional properties on PSP and heart rate through a molecular transmission to specific receptor site and bilipid layer physicochemical interations. Rapid uptake and slow release of THC in fat associated with a rate-limited uptake into brain may be a general philogenetic mechanism which would protect brain function from prolonged exposure to xenobiotics like THC and other fat soluble drugs. Copyright 2001 John Wiley & Sons, Ltd.

Psychoactive cannabinoids and membrane signaling.

THC-like psychoactive cannabinoids permeate the lipid bilayer of the membrane, altering its physicochemical properties and activating phospholipases. As a result, an increased production of arachidonic acid occurs with its cascade of eicosanoids, including prostaglandins. In addition, THC and its psychoactive derivatives bind within the membrane in a stereospecific fashion, to a transmembrane G protein coupled receptor (GPCR) for which THC has a much higher affinity than the natural ligands, arachidonylethanolamide (AEA) and 2-arachidonyglycerol (2-AG). These natural lipid ligands may be considered signaling molecules which are generated in the membrane lipid bilayer. THC alters the physicochemical disposition of the lipid bilayer and interacts with the integral membrane protein receptors through alteration of the boundary lipid. This effect is distinct from the mechanism resulting from its persistent binding to a G protein coupled transmembrane receptor. THC does not interact directly with neurotransmitter receptors but alters their pharmacological response in an allosteric fashion. It is proposed that the binding of AEA and 2-AG to the G protein coupled transmembrane receptor possesses a physiological function which is to regulate the signaling between boundary lipids and membrane receptors in response to extracellular signals. AEA and 2-AG are eicosanoid signaling molecules which modulate the activity of G protein coupled transmembrane receptors. AEA and 2-AG should not be identified with synthetic ligand molecules dubbed 'endogenous cannabinoids' which are 'xenobiotics' with no physiological regulating function. THC deregulates persistently a basic signaling mechanism of the membrane lipid bilayer and of its integrated receptors with resulting impairment of cellular function of brain, heart and male gonads. Copyright 2000 John Wiley & Sons, Ltd.