Recommendations for Cancer Prevention Trials Using Potentially Ototoxic Test Agents

2001 ◽  
Vol 19 (6) ◽  
pp. 1658-1663 ◽  
Author(s):  
Lawrence I. Shotland ◽  
Frank G. Ondrey ◽  
Kristen A. Mayo ◽  
Jaye L. Viner
Keyword(s):  
Clinical Care ◽  
Standardize Patient ◽  
Adverse Event Reporting ◽  
Hearing Sensitivity ◽  
Age Related ◽  
Baltimore Longitudinal Study ◽  
Investigational Agents ◽  
Audiologic Testing ◽  
Pharmacologic Agents

PURPOSE: Preventive oncology applies pharmacologic agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy, a process that may require administration of agents over long periods of time. Although ototoxicity may be a tolerable side effect of anticancer or antimicrobial therapy, even modest ototoxicity may not be acceptable in agents developed for preventive oncology that are routinely administered to subjects who neither are, nor necessarily will become, clinically ill.MATERIALS AND METHODS: Age-related shifts in hearing may occur over the course of longterm or open-ended therapy; consequently, age-adjusted norms enable researchers to better distinguish hearing loss caused by drugs from that caused by aging. Norms for hearing sensitivity are derived from the Baltimore Longitudinal Study of Aging and are the basis for the proposed audiologic monitoring recommendations.RESULTS: Audiologic monitoring recommendations are presented that standardize patient selection, adverse event reporting, posttreatment follow-up, and audiologic testing for potentially ototoxic investigational agents.CONCLUSION: These recommendations are applicable to trials of investigational agents as well as various classes of drugs used in routine clinical care.

scholarly journals 977. The Prevalence and Burden of Non-AIDS Co-Morbidities in Women with or At-risk for HIV Infection in the United States

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S36-S36
Author(s):  
Lauren F Collins ◽  
Anandi N Sheth ◽  
C Christina Mehta ◽  
Elizabeth T Golub ◽  
Phyllis C Tien ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Care ◽  
Laboratory Data ◽  
The United States ◽  
Self Report ◽  
Age Related ◽  
Persons Living With Hiv ◽  
Hiv Serostatus ◽  
Hiv Women

Abstract Background Age-related non-AIDS comorbidities (NACM) increasingly account for morbidity and mortality in persons living with HIV. The burden of NACM and its association with HIV is poorly described in women. Methods We analyzed data from HIV+ and at-risk HIV− participants who were followed in the Women’s Interagency HIV Study (WIHS) after 2009 (when >80% of participants used antiretroviral therapy). The prevalence of each NACM (defined by a combination of self-report, clinical measurements, and laboratory data) and the number of NACM were summarized at a most recent follow-up visit and were compared by age and HIV serostatus using unadjusted linear regression models. Results There were 3232 women (2309 HIV+, 923 HIV–) with a median follow-up of 15.3 years. The median age was 50 years, 65% were black, 38% currently smoked, 71% had ever used illicit drugs, 50% had annual income < $12,000, and median body mass index was 30 kg/m2. HIV+ women had a median CD4 count of 618 cells/mm3 and 66% had HIV viral suppression. Among 10 NACM evaluated, the following were more prevalent in HIV+ vs. HIV– women (all P < 0.01): psychiatric illness (57%/48%), liver disease (45%/26%), hyperlipidemia (40%/35%), bone disease (40%/33%), chronic kidney disease (15%/7%), and non-AIDS cancer (11%/7%). There was little difference in the prevalence of hypertension (66%/64%), lung disease (41%/43%), diabetes (22%/24%), and cardiovascular disease (19%/19%). Mean number of NACM was higher in HIV+ vs. HIV– women (3.6 vs. 3.0, P < 0.0001). Regardless of HIV serostatus, NACM burden significantly increased with age (P < 0.0001). Compared with women aged <40 of the same HIV serostatus, the estimated mean difference in NACM (HIV+/HIV–) for those 40–49, 50–59, ≥60 years was 1.1/0.7, 2.3/2.3, and 3.6/3.2, respectively (P < 0.0001 for all). Within-age-group comparisons revealed significantly greater NACM burden in HIV+ vs. HIV− women aged 40–49 years (P < 0.0001) and ≥60 years (P = 0.003), but not in those aged <40 or 50–59 years (HIV*age interaction P = 0.02) (figure). Conclusion NACM burden was high in both HIV+ and at-risk HIV– women, but higher in HIV+ women overall and in certain age groups. Accumulation of NACM has complex implications for clinical care, medication management, and healthcare screening that must be further examined in this population. Disclosures Anandi N. Sheth, MD, MS, Gilead Sciences, Inc.: Research Grant.

A Questionnaire Survey of Current Rehabilitation Practices for Adults With Normal Hearing Sensitivity Who Experience Auditory Difficulties

2020 ◽  
Vol 29 (4) ◽  
pp. 738-761
Author(s):  
Tess K. Koerner ◽  
Melissa A. Papesh ◽  
Frederick J. Gallun
Keyword(s):  
Hearing Aids ◽  
Questionnaire Survey ◽  
Patient Population ◽  
Clinical Care ◽  
Normal Hearing ◽  
Auditory Training ◽  
Training Methods ◽  
Hearing Sensitivity ◽  
Considerable Benefit ◽  
High Level

Purpose A questionnaire survey was conducted to collect information from clinical audiologists about rehabilitation options for adult patients who report significant auditory difficulties despite having normal or near-normal hearing sensitivity. This work aimed to provide more information about what audiologists are currently doing in the clinic to manage auditory difficulties in this patient population and their views on the efficacy of recommended rehabilitation methods. Method A questionnaire survey containing multiple-choice and open-ended questions was developed and disseminated online. Invitations to participate were delivered via e-mail listservs and through business cards provided at annual audiology conferences. All responses were anonymous at the time of data collection. Results Responses were collected from 209 participants. The majority of participants reported seeing at least one normal-hearing patient per month who reported significant communication difficulties. However, few respondents indicated that their location had specific protocols for the treatment of these patients. Counseling was reported as the most frequent rehabilitation method, but results revealed that audiologists across various work settings are also successfully starting to fit patients with mild-gain hearing aids. Responses indicated that patient compliance with computer-based auditory training methods was regarded as low, with patients generally preferring device-based rehabilitation options. Conclusions Results from this questionnaire survey strongly suggest that audiologists frequently see normal-hearing patients who report auditory difficulties, but that few clinicians are equipped with established protocols for diagnosis and management. While many feel that mild-gain hearing aids provide considerable benefit for these patients, very little research has been conducted to date to support the use of hearing aids or other rehabilitation options for this unique patient population. This study reveals the critical need for additional research to establish evidence-based practice guidelines that will empower clinicians to provide a high level of clinical care and effective rehabilitation strategies to these patients.

Biomarkers of Acromegaly and Growth Hormone Action

2020 ◽  
Vol 27 (12) ◽  
pp. 1231-1245
Author(s):  
Filippo Maffezzoni ◽  
Teresa Porcelli ◽  
Andrea Delbarba ◽  
Letizia Pezzaioli ◽  
Carlo Cappelli ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Biological Markers ◽  
Clinical Care ◽  
Hormone Deficiency ◽  
Surrogate Outcomes ◽  
Current State ◽  
Growth Hormone Action ◽  
Igf I ◽  
Definition Of

: Biological markers (biomarkers) play a key role in drug development, regulatory approval and clinical care of patients and are linked to clinical and surrogate outcomes. : Both acromegaly and Growth Hormone Deficiency (GHD) are pathological conditions related to important comorbidities that, in addition to having stringent diagnostic criteria, require valid markers for the definition of treatment, treatment monitoring and follow-up. GH and insulin-like growth factor-I (IGF-I) are the main biomarkers of GH action in children and adults while, in acromegaly, both GH and IGF-I are established biomarkers of disease activity. : However, although GH and IGF-I are widely validated biomarkers of GHD and acromegaly, their role is not completely exhaustive or suitable for clinical classification and follow-up. Therefore, new biological markers for acromegaly and GH replacement therapy are strongly needed. : The aim of this paper is to review and summarize the current state in the field pointing out new potential biomarkers for acromegaly and GH use/abuse.

scholarly journals The importance of maternal pregnancy vitamin D for offspring bone health: learnings from the MAVIDOS trial

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110069
Author(s):  
Rebecca J. Moon ◽  
Elizabeth M. Curtis ◽  
Stephen J. Woolford ◽  
Shanze Ashai ◽  
Cyrus Cooper ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Development ◽  
Controlled Trial ◽  
Clinical Care ◽  
Later Life ◽  
Vitamin D Supplementation ◽  
Public Health Policies ◽  
Positive Effects

Optimisation of skeletal mineralisation in childhood is important to reduce childhood fracture and the long-term risk of osteoporosis and fracture in later life. One approach to achieving this is antenatal vitamin D supplementation. The Maternal Vitamin D Osteoporosis Study is a randomised placebo-controlled trial, the aim of which was to assess the effect of antenatal vitamin D supplementation (1000 IU/day cholecalciferol) on offspring bone mass at birth. The study has since extended the follow up into childhood and diversified to assess demographic, lifestyle and genetic factors that determine the biochemical response to antenatal vitamin D supplementation, and to understand the mechanisms underpinning the effects of vitamin D supplementation on offspring bone development, including epigenetics. The demonstration of positive effects of maternal pregnancy vitamin D supplementation on offspring bone development and the delineation of underlying biological mechanisms inform clinical care and future public-health policies.

Aflibercept in real-life for the treatment of age-related macular degeneration using a treat and extend protocol: The Armada study

2021 ◽  
pp. 112067212110057
Author(s):  
Pierre Gascon ◽  
Prithvi Ramtohul ◽  
Charles Delaporte ◽  
Sébastien Kerever ◽  
Danièle Denis ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Real Life ◽  
Age Related Macular Degeneration ◽  
Cumulative Number ◽  
Treat And Extend ◽  
Treatment Interval ◽  
Age Related ◽  
Treatment Naïve ◽  
The Mean

Purpose: To report the visual and anatomic outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with aflibercept under a standardized Treat and Extend (T&E) protocol for up to 3 years of follow-up in “real-life” practice. Methods: This retrospective, observational, multicenter study included patients with treatment-naïve nAMD and at least 12 months of follow-up. T&E regimen adjustment was initiated after loading phase. At each visit best-corrected visual acuity (BCVA) and optical coherence tomography parameters were performed. Results: One hundred and thirty-six eyes of 115patients had at least 1 year of follow-up with 114 and 82 eyes completing at least 2 and 3 years of follow-up, respectively (mean follow-up duration: 2.7 ± 1.3 years). Mean age was 78.6 ± 8.6 years old and 52% were women. Mean BCVA increased from 60.6 ± 18.7 letters at diagnosis to 66.9 ± 16.2 letters at 1 year (+6.3 letters, p = 0.003) and remained stable throughout the follow-up period (63.1 ± 20.3 letters (+2.5, p = 0.1) and 64.0 ± 20.1 letters (+3.4, p = 0.27) at 2 and 3 years, respectively). The mean central retinal thickness decreased significantly from 358.2 ± 87.9 µm at baseline to 302 ± 71.7 µm at 12 months and maintained stable after 36 months of follow-up (297.1 ± 76 µm, p < 0.0001). Mean number of injections was 6.6 ± 2.2, 4.8 ± 1.9, and 5.6 ± 1.7 at 1, 2, and 3 years, respectively. Mean cumulative number of 16.4 ± 5.6 injections after 3 years. Mean treatment interval was 6.8 ± 2.5 weeks at 1 year. Eight-week and 12-week treatment interval were achieved in 59.5% and 19.1%, 65.8%, and 36.8% and 69.5% and 41.5% at 1, 2, and 3 years, respectively. Conclusions: Our study demonstrated that intravitreal injections of aflibercept initiated under a standardized T&E for patients with treatment-naïve nAMD allow for significant visual improvement at 12 months, which was maintained over a 3-year follow-up period.

scholarly journals Strategies to Integrate Genomic Medicine into Clinical Care: Evidence from the IGNITE Network

2021 ◽  
Vol 11 (7) ◽  
pp. 647
Author(s):  
Nina R. Sperber ◽  
Olivia M. Dong ◽  
Megan C. Roberts ◽  
Paul Dexter ◽  
Amanda R. Elsey ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Program Implementation ◽  
Clinical Care ◽  
Genomic Medicine ◽  
Implementation Strategies ◽  
Clinical Decision ◽  
Implementing Change ◽  
Implementation Outcomes ◽  
Planning Framework

The complexity of genomic medicine can be streamlined by implementing some form of clinical decision support (CDS) to guide clinicians in how to use and interpret personalized data; however, it is not yet clear which strategies are best suited for this purpose. In this study, we used implementation science to identify common strategies for applying provider-based CDS interventions across six genomic medicine clinical research projects funded by an NIH consortium. Each project’s strategies were elicited via a structured survey derived from a typology of implementation strategies, the Expert Recommendations for Implementing Change (ERIC), and follow-up interviews guided by both implementation strategy reporting criteria and a planning framework, RE-AIM, to obtain more detail about implementation strategies and desired outcomes. We found that, on average, the three pharmacogenomics implementation projects used more strategies than the disease-focused projects. Overall, projects had four implementation strategies in common; however, operationalization of each differed in accordance with each study’s implementation outcomes. These four common strategies may be important for precision medicine program implementation, and pharmacogenomics may require more integration into clinical care. Understanding how and why these strategies were successfully employed could be useful for others implementing genomic or precision medicine programs in different contexts.

scholarly journals Silent cerebral embolisation during TAVI: evolution, predictors and neurocognitive effects

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M De Carlo ◽  
R Liga ◽  
G.M Migaleddu ◽  
M Scatturin ◽  
C Spaccarotella ◽  
...  
Keyword(s):  
White Matter ◽  
Median Number ◽  
Funding Source ◽  
Private Company ◽  
Diffuse White Matter ◽  
Transcatheter Aortic Valve ◽  
Age Related ◽  
Cerebral Mri ◽  
Neurocognitive Evaluation

Abstract Background Most patients undergoing transcatheter aortic valve implantation (TAVI) develop silent cerebral ischemic lesions (SCIL) detectable at magnetic resonance imaging (MRI). The natural history and clinical relevance of SCIL are not well established. We aimed to assess the characteristics, predictors, evolution, and neurocognitive effects of SCIL. Methods Cerebral MRI was performed within 7 days before TAVI to assess baseline status and age-related white matter changes (ARWMC) score. MRI was repeated postoperatively to assess the occurrence, location, number and dimensions of SCIL. Patients developing SCIL underwent a third MRI at 3–5 months follow-up. A neurocognitive evaluation was performed before TAVI, at discharge and at 3-month follow-up. Results Of the 117 patients enrolled, 96 underwent a postprocedural MRI; SCIL were observed in 76% of patients, distributed in all vascular territories, with a median number of 2 lesions, median diameter 4.5 mm, and median total volume 140 mm3. Independent predictors of SCIL occurrence were a higher baseline ARWMC score and the use of self-expanding or mechanically-expanded bioprostheses. Among 47 patients who underwent follow-up MRI, only 26.7% of postprocedural SCIL evolved into a gliotic scar. SCIL occurrence was associated with a more pronounced transient neurocognitive decline early after TAVI and with a lower recovery at follow-up. Conclusions SCIL occur in the vast majority of patients undergoing TAVR and are predicted by a more diffuse white matter damage at baseline and by the use of non-balloon-expandable prostheses. Although most SCIL disappear within months, their occurrence has a limited but significant impact on neurocognitive function. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): unrestricted grants from Edwards Lifesciences SA, Nyon, Switzerland, and from Medtronic Italia SpA, Milan, Italy

scholarly journals Subthreshold laser treatment for reticular pseudodrusen secondary to age-related macular degeneration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giuseppe Querques ◽  
Riccardo Sacconi ◽  
Francesco Gelormini ◽  
Enrico Borrelli ◽  
Francesco Prascina ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Laser Treatment ◽  
Age Related Macular Degeneration ◽  
Short Term ◽  
Treated Area ◽  
Reticular Pseudodrusen ◽  
End Point ◽  
Age Related ◽  
Subthreshold Laser

AbstractThere is a lack of treatment aimed at the regression of reticular pseudodrusen (RPD) secondary to age-related macular degeneration (AMD). The aim of this prospective, pilot study is to evaluate the safety and short-term efficacy of subthreshold laser treatment (SLT) in patients affected by RPD secondary to dry AMD (dAMD). Twenty eyes of 20 patients (mean age 78.4 ± 6.8 years) with RPD secondary to dAMD were prospectively enrolled. All patients were treated in an extrafoveal area of 1.27 mm2 using end-point management yellow subthreshold laser and followed for 3 months. Best-corrected visual acuity was 0.140 ± 0.09 LogMAR at the baseline and no changes were observed during the follow-up (p = 0.232). No significant worsening was disclosed before and after the treatment analyzing the macular sensitivity of the treated area (p = 0.152). No topical and/or systemic side effects were disclosed during the 3-month follow-up. The distribution among the RPD stages changed after the treatment (p < 0.001). In detail, in the treated area, we observed a significant increase in the number of Stage 1 RPD during the follow-up (p = 0.002), associated with a significant decrease of Stage 3 RPD (p = 0.020). Outer nuclear layer (ONL) thickness analysis showed a significant increase after the treatment associated with RPD regression (p = 0.001). End-point management SLT appears a safe treatment for RPD secondary to dAMD, showing short-term safety outcomes. Our results suggest that SLT could be effective in inducing a RPD regression in terms of RPD stage and ONL thickening.

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