Clinical Pharmacogenomic <i>MT‐RNR1</i> Screening for Aminoglycoside‐Induced Ototoxicity and the Post‐Test Counseling Conundrum

Rigobello, Robert; Shaw, Jay; Ilg, Daniel; Zimmerman, Ryan M.; Edelmann, Lisa; Kornreich, Ruth; Scott, Stuart A.; Cody, Neal

doi:10.1002/cpt.2910

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…The association of many additional MT-RNR1 variants with AG ototoxicity have been proposed. However, for most of them, there is insufficient evidence to support their association with the risk of AG-associated hearing loss [ 38 ]. The clinical relevance of MT-RNR1 mutations can significantly vary.…”

Section: Antibiotics For Which the Role Of Genetics In Conditioning D...mentioning

confidence: 99%

Genetic Variations and Antibiotic-Related Adverse Events

Principi,

Petropulacos,

Esposito

2024

Pharmaceuticals

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Antibiotic-related adverse events are common in both adults and children, and knowledge of the factors that favor the development of antibiotic-related adverse events is essential to limit their occurrence and severity. Genetics can condition the development of antibiotic-related adverse events, and the screening of patients with supposed or demonstrated specific genetic mutations may reduce drug-related adverse events. This narrative review discusses which genetic variations may influence the risk of antibiotic-related adverse events and which conclusions can be applied to clinical practice. An analysis of the literature showed that defined associations between genetic variations and specific adverse events are very few and that, at the moment, none of them have led to the implementation of a systematic screening process for patients that must be treated with a given antibiotic in order to select those at risk of specific adverse events. On the other hand, in most of the cases, more than one variation is implicated in the determination of adverse events, and this can be a limitation in planning a systematic screening. Moreover, presently, the methods used to establish whether a patient carries a “dangerous” genetic mutation require too much time and waiting for the result of the test can be deleterious for those patients urgently requiring therapy. Further studies are needed to definitively confirm which genetic variations are responsible for an increased risk of a well-defined adverse event.

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Section: Antibiotics For Which the Role Of Genetics In Conditioning D...mentioning

confidence: 99%

Genetic Variations and Antibiotic-Related Adverse Events

Principi,

Petropulacos,

Esposito

2024

Pharmaceuticals

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“…Moreover, recognition of mitochondrial mutation (ie, mitochondrial encoded ribosomal RNR 1, MTRNR1) carriers has clinical implications for the prevention of aminoglycoside-induced HL (AIHL). 14 Meanwhile, researches exploring the ethical and social implications of clinical genetic screening are ongoing. 15 Newborn deafness gene screening (NDGS) is not a novel concept in China.…”

Section: How This Study Might Affect Research Practice or Policymentioning

confidence: 99%

Economic evaluation of newborn deafness gene screening as a public health intervention in China: a modelling study

Shu,

Gu,

Zhai

et al. 2024

bmjph

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BackgroundWhile global newborn hearing screening programmes (NHSP) are far from the optimal level, the combined hearing and genetic screening has emerged as an innovative approach of early healthcare interventions. There is a clear need for economic evaluation to establish whether newborn deafness gene screening (NDGS), currently mandated by many cities in China, is a good investment.MethodsA decision-tree model was constructed to simulate a hypothetical 10-million Chinese newborn cohort over a lifetime with three strategies: (1) no screening, (2) NHSP (standard screening) and (3) NHSP+NDGS (combined screening). The presence of permanent congenital hearing loss (PCHL) and genetic mutation were assigned at birth and held constant for all strategies. Input parameters were obtained from the Cohort of Deafness-gene Screening study and literature review. The government contract price for genetic screening was US$77/child. Outcomes of interest included the number of early diagnosed PCHL, prelingual deafness, total deafness, special education referral, incremental cost-effectiveness ratio (ICER) and benefit–cost ratio (BCR).ResultsBoth standard and combined screening strategies were more effective and more costly than ‘no screening’. Compared with standard screening, combined screening led to 9112 (28.0%) more PCHL cases early detected, avoiding 4071 (66.9%) prelingual deafness cases and 3977 (15.6%) special education referrals. The ICER and BCR for combined screening were US$ 4995/disability-adjusted life-year (95% uncertainty interval, 2963 to 9265) and 1.78 (1.19 to 2.39), from healthcare sector perspective. Combined screening would dominate standard screening from societal perspective. Moreover, it remained cost-effective even in pessimistic scenarios.ConclusionsOur findings have particular implication for the ‘scale-up’ of genetic screening at the national level in China. The model may serve as a feasible example for hearing screening strategies in other countries, as well as genetic screening for other diseases.

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“…Ototoxicity and nephrotoxicity are signi cant as they can result in permanent hearing loss and renal damage [10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey

Arribas,

Decembrino,

Raffaeli

et al. 2024

Eur J Pediatr

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Background. Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian NICUs.Methods. A prospective cross-sectional study was conducted in Italian and Spanish NICUs using a webbased survey with 43 questions. A modi ed Delphi method involved experts re ning the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring.Results. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices.Conclusions. The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in NICUs. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe.The Joint Committee on Infant Hearing (JCIH) identi es ototoxic drugs like aminoglycosides and loop diuretics as risk indicators for hearing loss, so hearing screening is recommended [18; 19]. Recently, vancomycin was linked to hearing loss in very low birth weight infants [20].Apart from previously mentioned drugs, potential ototoxic and nephrotoxic agents encompass antibiotics (e.g., piperacillin/tazobactam), nonsteroidal anti-in ammatory drugs (indomethacin, ibuprofen), antivirals (acyclovir), antifungals (amphotericin B), angiotensin-converting enzyme inhibitors (captopril, enalapril), and spironolactone [21][22][23][24][25][26][27][28][29][30].Newborns on these drugs require close kidney function monitoring for acute kidney injury (AKI) and chronic kidney disease (CKD). A single-center study revealed that 70% of children had lasting kidney damage after nephrotoxic medication-induced AKI [31]. However, diagnosing drug-induced AKI (D-AKI) is complex due to varying criteria, hindering accurate identi cation [32][33][34].Considering that the above-mentioned drugs are among the most commonly used in neonatology, we conducted a survey in Spanish and Italian neonatal units on the use and management of drugs with a higher...

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Clinical Pharmacogenomic MT‐RNR1 Screening for Aminoglycoside‐Induced Ototoxicity and the Post‐Test Counseling Conundrum

Cited by 4 publications

References 9 publications

Genetic Variations and Antibiotic-Related Adverse Events

Genetic Variations and Antibiotic-Related Adverse Events

Economic evaluation of newborn deafness gene screening as a public health intervention in China: a modelling study

Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey

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