The Lived Experience of Pediatric Gene Therapy: A Scoping Review.

Little is known about patients' and families' lived experiences of participating in pediatric gene therapy (GT) clinical trials. Currently, pediatric GT research targets a broad range of indications--including rare and ultra-rare diseases--which vary in severity and in the availability of alternative therapies. Pediatric GT differs meaningfully from adult GT because the decision to participate involves a dyad of both the child and parent or caregiver/s. It is critical to understand patients' and caregivers' perceptions and experiences of social, emotional, physical, and logistical burdens or benefits of participating in such trials, and how they weigh and prioritize these factors when deciding whether to participate. We conducted a scoping review of the current literature in this subject area with objectives to (1) provide an overview of existing literature, (2) identify gaps and areas for further research, and (3) better understand the lived impact of pediatric GT research on patients and their parents/caregivers. Four themes emerged, including (1) weighing risks and benefits (2) timing of GT trial participation, (3) value of clear communication, and (4) potential impact on quality of life. Notably, our sample surfaced articles about how patients/parents/caregivers were thinking about GT-their understanding of its safety, efficacy, and risks-rather than accounts of their experiences, which was our initial intention. Nevertheless, our findings offer useful insights to improve the informed consent process and promote a more patient- and family-centered approach. Moreover, our findings can contribute to patient advocacy organizations' efforts to develop educational materials tailored to patients' and families' expressed informational needs and perspectives, and can inform more patient- and family-centered policies from GT clinical trial sponsors.

Environmental influences on ophthalmic conditions: A scoping review.

BACKGROUND: Environmental factors have been implicated in various eye pathologies. The purpose of this review is to synthesise the published research on environmental effects on eye disease. METHODS: Four databases were searched for terms relating to environmental exposures and ophthalmic disease. Titles and abstracts were screened followed by full-text review. Data was extracted from 118 included studies. Quality assessment was conducted for each study. RESULTS: Air pollutants, including nitrogen dioxide, nitrites, sulphur dioxide, particulate matter, carbon monoxide, ozone and hydrocarbons are associated with ocular conditions ranging from corneal damage to various retinopathies, including central retinal artery occlusion. Certain chemicals and metals, such as cadmium, are associated with increased risk of age-related macular degeneration. Climate factors, such as sun exposure, have been associated with the development of cataracts. Living in rural areas was associated with various age-related eye diseases whereas people living in urban settings had higher risk for dry eye disease and uveitis. CONCLUSION: Environmental exposures in every domain are associated with various ophthalmic conditions. These findings underscore the importance of continued research on the interplay between the environment and eye health.

Health literacy and ophthalmology: A scoping review.

As of 2020, it is estimated that 43.3 million people are blind, and an additional 553 million have mild to severe vision impairment.50 At least 1 billion worldwide have a vision impairment that could have been prevented or has yet to be addressed.54 Poor health literacy may be a significant contributor to the prevalence of eye disease. With implications on disease burden, progression, and health outcomes, a greater understanding of the role health literacy plays in ophthalmology is needed. This is the first scoping review to assess the impact of health literacy on eye health outcomes and blindness, including ocular screening rates and/or follow-up rates, treatment adherence, and self-care practices. PubMed, Embase, and CINAHL databases were searched systematically through November 12, 2021, and we evaluated the association between health literacy and ophthalmic outcomes in 4 domains: clinical outcomes, treatment adherence rates, screening and/or follow-up rates, and self-care practices. There is evidence to suggest that health literacy is associated with ophthalmic outcomes in all these domains. To better understand how health literacy impacts eye health, further longitudinal studies examining the effect of health literacy (using standardized health literacy measures) on ophthalmic outcomes are needed. We believe a specific ophthalmic health literacy survey could help achieve this goal and help target interventions to ultimately improve outcomes among ophthalmology patients.

Outcomes of primary root canal therapy: An updated systematic review of longitudinal clinical studies published between 2003 and 2020.

BACKGROUND: A comprehensive effort to evaluate outcomes of primary root canal therapy (RCT) between 1966 and 2002 was published by Ng et al. (2007, International Endodontic Journal, 40, 921; 2008, International Endodontic Journal, 41, 6). Changes in endodontic materials and treatment methods warrant an updated analysis of outcomes. OBJECTIVES: This study aimed to (1) quantify the success rates of primary RCT published between 2003 and 2020; and (2) investigate the influence of some characteristics known/suspected to be associated with treatment outcomes. METHODS: An electronic search was performed in the following databases (01-01-2003 to 12-31-2020): Pubmed, Embase, CINHAL, Cochrane and Web of Science. Included study designs were longitudinal clinical studies (randomized control trials, cohort studies, retrospective observational studies). Studies with at least twelve-months of post-operative review and success rates based on clinical and radiographic criteria were analysed. The terms 'strict' (complete resolution of periapical lesion) or 'loose' (reduction in size of existing periapical lesion) were used to describe the outcome criteria. Weighted, pooled success rates were calculated. Random effects meta-regression models were used to investigate potential sources of statistical heterogeneity. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate for quality assessment of the included studies. RESULTS: Forty-two studies were included in the review. Meta-analyses showed that the weighted pooled success rates were estimated to be 92.6% (95% CI: 90.5%-94.8%) under 'loose criteria' and 82.0% (95% CI: 79.3%-84.8%) under 'strict' criteria. The most significant areas of study heterogeneity were year of publication and qualification of operator. The majority (64.29%) of studies were considered to be of low quality of evidence. DISCUSSION: Biological factors continue to have the most significant impact on RCT outcomes. The technological method of instrumentation had no significant effect. The quality of evidence was based primarily on study design and only randomized control trials were considered to be 'high' quality of evidence. CONCLUSIONS: The reported success rates show improvement over time. Weighted success rates for studies with a minimum of four-years follow-up had better outcomes, compared to those with less than four years, when 'strict criteria' were used. REGISTRATION: PROSPERO database (CRD42021226311).

Virtual Reality and Augmented Reality in Ophthalmology: A Contemporary Prospective.

PURPOSE: Most published systematic reviews have focused on the use of virtual reality (VR)/augmented reality (AR) technology in ophthalmology as it relates to surgical training. To date, this is the first review that investigates the current state of VR/AR technology applied more broadly to the entire field of ophthalmology. METHODS: PubMed, Embase, and CINAHL databases were searched systematically from January 2014 through December 1, 2020. Studies that discussed VR and/or AR as it relates to the field of ophthalmology and provided information on the technology used were considered. Abstracts, non-peer-reviewed literature, review articles, studies that reported only qualitative data, and studies without English translations were excluded. RESULTS: A total of 77 studies were included in this review. Of these, 28 evaluated the use of VR/AR in ophthalmic surgical training/assessment and guidance, 7 in clinical training, 23 in diagnosis/screening, and 19 in treatment/therapy. 15 studies used AR, 61 used VR, and 1 used both. Most studies focused on the validity and usability of novel technologies. CONCLUSIONS: Ophthalmology is a field of medicine that is well suited for the use of VR/AR. However, further longitudinal studies examining the practical feasibility, efficacy, and safety of such novel technologies, the cost-effectiveness, and medical/legal considerations are still needed. We believe that time will indeed foster further technological advances and lead to widespread use of VR/AR in routine ophthalmic practice.

What is the societal economic cost of poor oral health among older adults in the United States? A scoping review.

OBJECTIVE: To assess the state of the literature in the United States quantifying the societal economic cost of poor oral health among older adults. BACKGROUND: Proponents of a Medicare dental benefit have argued that addressing the growing need for dental care among the US older adult population will decrease costs from systemic disease and other economic costs due to oral disease. However, it is unclear what the current economic burden of poor oral health among older adults is in the United States. METHODS: We conducted a scoping review examining the cost of poor oral health among older adults and identified cost components that were included in relevant studies. RESULTS: Other than oral cancer, no studies were found examining the economic costs of poor oral health among older adults (untreated tooth decay, gum disease, tooth loss and chronic disease/s). Only two studies examining the costs of oral cancer were found, but these studies did not assess the full economic cost of oral cancer from patient, insurer and societal perspectives. CONCLUSIONS: Future work is needed to assess the full economic burden of poor oral health among older adults in the United States, and should leverage novel linkages between medical claims data, dental claims data and oral health outcomes data.

Anti-IL-6 Therapies for Neuromyelitis Optica Spectrum Disorders: A Systematic Review of Safety and Efficacy.

BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD) is a chronic autoimmune disease of the central nervous system that causes recurrent attacks of optic neuritis, myelitis, and brainstem symptoms, resulting in severe neurological disability. Preventive treatment with immunosuppressive agents reduces relapse rate and improves long-term prognosis. In recent years, the potential therapeutical effect of new agents has been investigated. Two of these, the anti-interleukin 6 (IL-6) agents tocilizumab and satralizumab, have been studied in active NMOSD. OBJECTIVE: To systematically review the current data regarding the efficacy and safety of anti-IL-6 agents in NMOSD. RESULTS: Fourteen case reports and 5 case series of intravenous tocilizumab have shown beneficial clinical and paraclinical effects compared to commonly used therapies, and another case series of subcutaneous tocilizumab has shown it is as effective as the IV formulation. A phase 2 comparative trial has shown tocilizumab IV to be more effective than azathioprine for relapse prevention. A phase 3 trial of subcutaneous satralizumab versus placebo, has shown a lower risk of relapse in the sartralizumab-treated group, both as add-on therapy to stable immunosuppressant and as monotherapy. Tocilizumab also reduced pain severity in two trials and fatigue scores in one trial, but satralizumab did not significantly improve pain and fatigue. Adverse events with both agents were relatively mild and comparable to placebo and azathioprine. CONCLUSION: The anti-Il-6 agents tocilizumab and satralizumab show promising results in active NMOSD. Further randomized, larger-scale trials are needed to better define the role of these agents in the growing arsenal of NMOSD treatments.

Patient Extratherapeutic Interpersonal Problems and Response to Psychotherapy for Depression.

OBJECTIVES: This paper aimed to synthesize empirical findings of patient extratherapeutic interpersonal variables associated with individual psychotherapy treatment outcomes in adult outpatients with depression. METHODS: A systematic search strategy was used to identify relevant studies. Thematic analysis was used to identify recurring themes in the findings. RESULTS: Forty studies met search criteria. Three themes of patient extratherapeutic interpersonal variables were identified: capacity to engage with others, capacity to navigate relationships, and capacity to achieve intimacy, progressing from basic to advanced levels of interpersonal interaction. Interpersonal variables such as interpersonal distress and style, attachment orientation, and quality of object relations were particularly useful in predicting treatment outcomes, whereas access to social support and marital status provided mixed results, likely because they do not account for relationship quality. CONCLUSIONS: Recognizing variables associated with treatment response can help clinicians identify patients at risk for nonresponse and guide efforts for adapting existing therapies and developing new ones.

A systematic review on incidental findings in cone beam computed tomography (CBCT) scans.

OBJECTIVES: Cone beam CT's use (CBCT) in dentistry is increasing. Incidental findings (IFs: discoveries unrelated to the original purpose of the scan), are frequently found as a result of a large field of view. The aim of the systematic review is to analyze present literature on IFs using CBCT. METHODS AND MATERIALS: The authors searched online databases of studies and assessed the prevalence of IFs among patients undergoing head and neck CBCT scans. STROBE criteria was used to evaluate the quality of the studies. RESULTS: The original search retrieved 509 abstracts of which only 10 articles met the inclusion criteria. The sample size varied between 90 and 1000 participants. The frequency of IFs of the selected articles were 24.6-94.3%. The most common non-threatening IFs were found in the airway, such as mucous retention cyst (55.1%) and sinusitis (41.7%). Other non-threatening IFs were soft tissue calcifications such as calcified stylohyloid ligament (26.7%), calcified pineal gland (19.2%), and tonsillolith (14.3%). Threatening IFs were rare findings (1.4%). Three articles reported incidental carotid artery calcifications with a prevalence of 5.7-11.6%. Pathological findings were not common between the articles, but still relevant (2.6%). The studies had a risk of bias varying from moderate to low. CONCLUSIONS: There is a high frequency of IFs, yet not all of them require immediate medical attention. The low prevalence of threatening IFs emphasizes that CBCT should not be considered a substitution for conventional radiographs, but when used, the scans should be evaluated by a maxillofacial radiologist.

Exposure to benzophenone-3 and reproductive toxicity: A systematic review of human and animal studies.

Hydroxy-4-methoxybenzophenone, also known as benzophenone-3 (BP-3), is a commonly used ultraviolet filter in skincare and as a food additive. Large concentrations of similar phenolic compounds have been detected in urine, amniotic fluid, and placental tissue, thereby raising questions about its impact on reproduction. The objective of this paper was to investigate the reproductive toxicity of BP-3 in humans and animals. In humans, studies showed that high levels of BP-3 exposure could be linked to an increase in male birth weight but a decline in female birth weight and male gestational age. In fish, BP-3 exposure resulted in a decline in egg production, hatching, and testosterone, along with a down-regulation of steroidogenic genes. In rats, a decrease in epididymal sperm density and a prolonged estrous cycle for females was observed. These positive associations may be attributed to an altered estrogen and testosterone balance as a result of endocrine disrupting effects of BP-3. However, the current body of literature is limited by non-uniform exposure and outcome measurements in studies both across and within species and future studies will need to be conducted in a standardized fashion to allow for a more significant contribution to the literature that allows for better comparison across studies.

A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI.

BACKGROUND: Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist. OBJECTIVE: Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. DATA SOURCES: Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. LIMITATIONS: While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search. CONCLUSIONS: We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.

World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment.

OBJECTIVES: Medication-induced salivary gland dysfunction (MISGD) causes significant morbidity resulting in decreased quality of life. This systematic review assessed the literature on the prevalence, diagnosis, treatment, and prevention of MISGD. MATERIALS AND METHODS: Electronic databases were searched for articles related to MISGD through June 2013. Four independent reviewers extracted information regarding study design, study population, interventions, outcomes, and conclusions for each article. Only papers with acceptable degree of relevance, quality of methodology, and strength of evidence were retained for further analysis. RESULTS: There were limited data on the epidemiology of MISGD. Furthermore, various methods were used to assess salivary flow rate or xerostomia. Preventive and therapeutic strategies included substitution of medications, oral, or systemic therapy with sialogogues, use of saliva substitutes or of electro-stimulating devices. Although there are promising approaches to improve salivary gland function, most studies are characterized by small numbers and heterogeneous methods. CONCLUSIONS: Physicians and dentists should identify the medications associated with xerostomia and salivary gland dysfunction through a thorough medical history. Preferably, health care providers should measure the unstimulated and stimulated whole salivary flow rates of all their patients so that these values can be used as a baseline to rate the complaints of patients who subsequently claim to experience xerostomia or salivary gland dysfunction as well as the possibilities of effectively treating this condition. CLINICAL RELEVANCE: MISGD remains a major burden for the population. This systematic review provides a contemporary in-depth description of the diagnosis and treatment of MISGD.

World Workshop on Oral Medicine VI: clinical implications of medication-induced salivary gland dysfunction.

OBJECTIVE: This study aimed to systematically review the available literature on the clinical implications of medication-induced salivary gland dysfunction (MISGD). STUDY DESIGN: The systematic review was performed using PubMed, Embase, and Web of Science (through June 2013). Studies were assessed for degree of relevance and strength of evidence, based on whether clinical implications of MISGD were the primary study outcomes, as well as on the appropriateness of study design and sample size. RESULTS: For most purported xerogenic medications, xerostomia was the most frequent adverse effect. In the majority of the 129 reviewed papers, it was not documented whether xerostomia was accompanied by decreased salivary flow. Incidence and prevalence of medication-induced xerostomia varied widely and was often associated with number and dose of medications. Xerostomia was most frequently reported to be mild-to-moderate in severity. Its onset occurred usually in the first weeks of treatment. There was selected evidence that medication-induced xerostomia occurs more frequently in women and older adults and that MISGD may be associated with other clinical implications, such as caries or oral mucosal alterations. CONCLUSIONS: The systematic review showed that MISGD constitutes a significant burden in many patients and may be associated with important negative implications for oral health.

Leveraging technology and staffing in developing a new liaison program.

With nearly all library resources and services delivered digitally, librarians working for the New York University Health Sciences Library struggled with maintaining awareness of changing user needs, understanding barriers faced in using library resources and services, and determining knowledge management challenges across the organization. A liaison program was created to provide opportunities for librarians to meaningfully engage with users. The program was directed toward a subset of high-priority user groups to provide focused engagement with these users. Responsibility for providing routine reference service was reduced for liaison librarians to provide maximum time to engage with their assigned user communities.

A longitudinal study of very young children's vowel production.

PURPOSE: Ecologically realistic, spontaneous, adult-directed, longitudinal speech data of young children were described by acoustic analyses. METHOD: The first 2 formant frequencies of vowels produced by 6 children from different American English dialect regions were analyzed from ages 18 to 48 months. The vowels were from largely conversational contexts and were classified according to dictionary pronunciation. RESULTS: Within-subject formant frequency variability remained relatively constant for the span of ages studied. It was often difficult to detect overall decreases in the first 2 formant frequencies between ages 30 and 48 months. A study of the movement of the corner vowels with respect to the vowel centroid showed that the shape of the vowel space remained qualitatively constant from 30 through 48 months. CONCLUSIONS: The shape of the vowel space is established early in life. Some aspects of regional dialect were observed in some of the subjects at 42 months of age. The present study adds to the existing data on the development of vowel spaces by describing ecologically realistic speech.

Prevention of root caries: a literature review of primary and secondary preventive agents.

PURPOSE: This literature review summarizes the effectiveness of the seven leading root caries preventive agents and provides recommendations for use of those agents in clinical practice with older adults and vulnerable elderly. METHOD: Studies were eligible if they assessed the effectiveness of either fluoride, chlorhexidine, xylitol, amorphous calcium phosphate, sealants, saliva stimulators, or silver diamine fluoride to prevent/control root caries in an English language articles between 1979 and 2010. RESULTS: In the 31 eligible studies, the most effective primary (1°) prevention agents had reductions in RC incidence ranging from 72% to nearly 200% as compared to a placebo while for secondary (2°) prevention, the best agents demonstrated arrest rates between 67 and 80%. CONCLUSION: For 1° prevention of root caries the recommended "best choice" is a 38% Silver Diamine Fluoride solution professionally applied annually, while for the 2° prevention of root caries, the recommended "best choice" is a 22,500 ppm Sodium Fluoride varnish professionally applied every 3 months.

Implications of peripheral muscular and anatomical development for the acquisition of lingual control for speech production: a review.

OBJECTIVES: Normally developing children learn to produce intelligible speech during rapid, non-uniform growth of their articulators and other vocal tract structures. The purpose of this review is to focus attention on the consequences of peripheral growth and development for the acquisition of lingual control for speech production. This paper (1) reviews physiological underpinnings of tongue shaping and movements that are likely to be changing in young children; (2) estimates, from previously published studies, the net consequences of growth of multiple vocal tract structures on lingual control; (3) integrates our findings with the example of [R] production, and (4) highlights areas where further investigations would be most helpful. PATIENTS AND METHODS: The authors searched the literature, including the PubMed database, for studies of the development of muscle proteins, muscle fibers, and motor units of the tongue, and of the growth of the tongue, jaw, adenoids, soft and hard palates, oral and pharyngeal cavities, and the vocal tract as a whole. CONCLUSIONS: Substantial anatomical and muscular data sets focused on children from 1-4 years of age, and rigorous definitions of the tongue boundaries are needed.

Source-tract interaction with prescribed vocal fold motion.

An equation describing the time-evolution of glottal volume velocity with specified vocal fold motion is derived when the sub- and supra-glottal vocal tracts are present. The derivation of this Fant equation employs a property explicated in Howe and McGowan [(2011) J. Fluid Mech. 672, 428-450] that the Fant equation is the adjoint to the equation characterizing the matching conditions of sub- and supra-glottal Green's functions segments with the glottal segment. The present aeroacoustic development shows that measurable quantities such as input impedances at the glottis, provide the coefficients for the Fant equation when source-tract interaction is included in the development. Explicit expressions for the Green's function are not required. With the poles and zeros of the input impedance functions specified, the Fant equation can be solved. After the general derivation of the Fant equation, the specific cases where plane wave acoustic propagation is described either by a Sturm-Liouville problem or concatenated cylindrical tubes is considered. Simulations show the expected skewing of the glottal volume velocity pulses depending on whether the fundamental frequency is below or above a sub- or supra-glottal formant. More complex glottal wave forms result when both the first supra-glottal fundamental frequencies are high and close to the first sub-glottal formant.

A study of high front vowels with articulatory data and acoustic simulations.

The purpose of this study is to test a methodology for describing the articulation of vowels. High front vowels are a test case because some theories suggest that high front vowels have little cross-linguistic variation. Acoustic studies appear to show counterexamples to these predictions, but purely acoustic studies are difficult to interpret because of the many-to-one relation between articulation and acoustics. In this study, vocal tract dimensions, including constriction degree and position, are measured from cinéradiographic and x-ray data on high front vowels from three different languages (North American English, French, and Mandarin Chinese). Statistical comparisons find several significant articulatory differences between North American English /i/ and Mandarin Chinese and French /i/. In particular, differences in constriction degree were found, but not constriction position. Articulatory synthesis is used to model the acoustic consequences of some of the significant articulatory differences, finding that the articulatory differences may have the acoustic consequences of making the latter languages' /i/ perceptually sharper by shifting the frequencies of F(2) and F(3) upwards. In addition, the vowel /y/ has specific articulations that differ from those for /i/, including a wider tongue constriction, and substantially different acoustic sensitivity functions for F(2) and F(3).