The results also indicate significant variability across operationsfor a single commodity. The interquartile range of RMRs for individualcobalt operations, for example, varies from 465 to 2157, with a globalRMR of 859. RMR variability is mainly driven by ore grades and revenuecontribution. The total attributable ore mined and waste rock removedin the production of these 25 commodities sums to 37.6 billion metrictons, 83% of which is attributable to iron ore, copper, and gold.RMRs provide an additional dimension for evaluating the impact ofmaterials and material choice trade-offs. The results can enhancelife cycle inventories and be extended to evaluate areas of surfacedisturbances, mine tailings, energy requirements, and associated greenhousegas emissions.The quantity of oremined and waste rock  removed to produce a refined unit of a mineral commodity, itsrock-to-metal ratio (RMR), is an important metric for understandingmine wastes and environmental burdens. In this analysis, we providea comprehensive examination of RMRs for 25 commodities for 2018. Theresults indicate significant variability across commodities. Preciousmetals like gold have RMRs in the range of 10 Spanning 8 orders of magnitudeacross 25 mineral commoditiesand nearly 2000 operations, the quantity of ore mined and waste rockremoved to produce a refined mineral commodity unit provides an additionaldimension for evaluating the impact of materials and material choicetrade-offs. A heavymineral sands operation producing titanium may, for example, requirethe extraction of large amounts of ore and waste rock, but the associatedenvironmental impacts are likely small because the tailings are relativelyinert and usually are used to backfill and restore the open pit. Incontrast, an underground nickel sulfide mine might extract relativelylow volumes of ore and waste rock but may pose considerable environmentalchallenges due to the potential for acid mine drainage from the tailings.3 Nevertheless, quantifying the flows of ore andwaste during mining and processing is increasingly necessary for understandingnot only the potential environmental impacts but also the currentand future supply of these mineral commodities, especially as demandfor mineral commodities increases and ore grades decline.Mining of metallicand industrial minerals represents a volumetricallysignificant flow of material from the lithosphere to the anthroposphere.A direct relationship exists between the amount of material minedand the complexities of extracting, transporting, and transformingnaturally occurring rocks into mineral commodities. The quantity ofmaterial mined, together with qualities such as ore grade, mineralogy,depth, and location, determines certain aspects of the environmentalburdens associated with mineral commodity production. For example,as ore grades of mineral commodities decline, the amount of materialthat must be extracted to produce a certain amount of the commodityincreases and its processing requires a greater amount of energy andother inputs.6 The value ofthese techniques is, however, limited by the availability of reliableand representative data. While some information on the quantitiesof ore mined and waste rock removed are reported periodically by theU.S. Geological Survey (USGS),7 these dataare limited to operations in the United States. Additionally, dueto concerns regarding the release of company proprietary information,the USGS data are aggregated so that it is impossible to determinethe variability between operations. Previous studies on the TMR formineral ores,9 although quite comprehensive interms of the number of elements examined, are single point estimatesbased only on an assumed average ore grade  and an assumedstripping ratio  of 2 acrossall commodities. Similarly, commercially available life cycle inventories(LCI)  typically relyon one or a few representative operations or presumed global averages.While these may be reasonable assumptions when no other data are availablethe degree of variability between operations is not known or well-quantified.Assessmentsof the total material requirement (TMR) aim to identifythese impacts by explicitly quantifying the “hidden”mass flows associated with extractive operations.11 a similar but orthogonal metric for material use would help bringto the fore the impact of mined material consumption.For the mining and processing of mineral commodities, the quantityof rock required to be mined varies significantly by commodity anddeposit, and depends on factors including ore grades, deposit type,mining method , ore body depth, andstripping ratios even for a single mineral commodity. Having granular,operation-level information can thus help in not only understandingthe variability in the data but can also assist companies in makinginformed decisions regarding, for example, where they source theirraw materials. In this vein, there is a need for methodologicallyconsistent and comprehensive data to enable accounting of companies’raw material footprints in the same way companies assess their carbonfootprints. A means to quantify TMR comprehensively would also addto the growing body of literature that considers environmental metricsneeded to quantify material criticality, circularity, and sustainability.Using global warming potential (GWP) as a life cycle metric has helpedto normalize the concept of carbon impacts;The mainobjective of this work thus is to develop a contemporaryand globally representative estimate for the total amount of materialthat must be displaced to produce a given mineral commodity. Specifically,the goal is to determine the amount of waste rock, tailings, and processinglosses generated during the production of a unit of finished metal:a rock-to-metal ratio (RMR). Additionally, this work aims to improvethe understanding of the variability around this ratio and the underlyingfactors that control it. In this work, the RMR methodology was appliedto 25 mineral commodities: aluminum (bauxite), chromium, cobalt, copper,gallium, gold, iridium, iron, lithium, magnesium , molybdenum,nickel, palladium, platinum, rhodium, ruthenium, silicon, silver,tantalum, tin, titanium, tungsten, vanadium, zinc, and zirconium.Although these commodities were selected mainly on the basis of dataavailability, the diversity of their sources and uses provides a strongfoundation for understanding the drivers and variability among thekey parameters, which in turn provides essential information to understandingcurrent and future supply potential and associated environmental impacts.i and mining operation j, O is thequantity of ore mined, W is the quantity of wasterock removed, M is the quantity of mineral commodityproduced at the mine after beneficiation , R is the overall recoveryrate during smelting and (or) refining (referred to as refinery recoveryrate for simplicity), and P is the realized unitprice of the commodity.The RMR was calculated using the following equation:The RMR can be calculated for a singleoperation or aggregatedto any desired level, including the global level, by summing acrossoperations for a given year as illustrated in Table S1). For some commodities, the system boundaryincluded multiple refined end products . In all situations, theend product production quantity is reported in terms of commoditymaterial-contained.For each mineral commodity, a systemboundary was defined. Each system included the mining and processingstages beginning with extraction of raw material at the mine site(run-of-mine) and ending with the production of the first or mostcommon marketable refined end-product for each commodity  are included in the RMR calculation.Similarly, magnesium metal is produced from brine and hard rock sources.Accordingly, the RMR was calculated only for magnesium metal productionfrom evaporite minerals and carbonate rock. Metal production fromash and waste residues was also excluded. Similarly, operations that reprocess mine tailingsto recovery mineral commodities were excluded because the ore wasmined in previous years. Technically, any reprocessed mine tailingsshould reduce the RMR calculation of the previous year. Most of theseoperations contribute little to global production and were thus excludedin this analysis.12 Relevant available dataincluded annual ore production tonnages, mill-head grades, strippingratios, and concentrator recovery rates. These data were either directlyreported in corporate publications such as annual and quarterly companyreports and presentations and U.S. Securities and Exchange Commissionfilings or their equivalent or derived by S&P Global Market Intelligencefrom information on similar operations.Where possible, theparameters of the RMR eq  than the USGS published estimates. In such instances,we calculated the share of global production based on the revisedglobal production totals that better reflect current data availability.For each individualentry, we also calculated its share of global production for the commoditiesthat it produced. The primary source of total global commodity productiondata, including at the country-level, was the USGS.Because of the corporate focus of the SNL data, global coveragevaried notably by commodity with special emphasis on operational-levelreporting for precious metals and the major base metals. In contrast,minor metals such as tungsten and tantalum had minimal reporting.For example, the sum of all copper production reported at the operational-levelwas within 6% of global copper production reported by the USGS, whereasno operational-level production data were reported for tantalum. Thecorporate focus of the SNL data was also biased toward commodity productionfrom either large or publicly traded firms, resulting in a lack ofdata from state-owned enterprises and noncorporate artisanal operations.Furthermore, the necessary data were not available for all operationsof a given commodity. In such cases, we calculated the RMR using thebest available data and, if necessary, adjusted the calculation toaccount for as large of a fraction of global production as possibleto obtain a more representative RMR. For example, data for nickelwere available for some but not all operations in Indonesia. An RMRfor an “Indonesia-remainder” was calculated using thebest available information on nickel deposits in Indonesia for theportion of that country’s nickel production that cannot becalculated for individual operations. Similar calculations were madefor other countries and other commodities.Figure S1). The global coverage of reported, calculated, and estimateddata for each RMR parameter is provided in Additionally, someoperations had data for some but not all theparameters in the RMR calculation. The quantity of waste rock removed,for example, is not typically reported by operators. In such instances,these quantities were calculated based on concentrator recovery rates,ore grades, and waste-to-ore ratios. For example, if a mining operation’sconcentrate production was reported, the quantity of ore that wasmilled can be calculated by dividing the concentrate production bythe concentrator recovery rate and the mill-head grade. If the mill-headgrade was not available, a reported ore grade for proven or probablereserves was used as an alternative. Although stockpiling is commonpractice, the quantity of ore milled was typically assumed to equalthe quantity of ore mined . This necessary assumption effectively means thatthe resultant RMR is specific to the ore that was milled that yearrather than what ore was mined or waste rock was removed in that particularyear. In general, most mines process the mined ores in the same yearmaking this a minor systems boundary issue. Finally, the quantityof waste rock removed can be estimated from the quantity of ore minedif the waste-to-ore ratio was also available. This approach of startingfrom a mine’s concentrate production and back-calculating thequantity of ore mined and waste rock removed was the predominant methodused. To aid in this process, a decision tree was developed to determinehow RMR parameters should be estimated in the absence of directlyreported quantities or the inability to calculate the quantities fromthe relevant factors  see S1. The g19 industry reports, and geologic publications. Additional detailsregarding these special cases are provided in the following section.As illustrated in Table S1. For example,the RMR for magnesium includes only hard rock sources and thus excludesmagnesium from brines. It is also specific to magnesium metal andexcludes magnesium compounds. RMRs should thus only be interpretedas representative for the system boundaries and end products thatare covered in the analysis.The overall coverage should be interpreted as the global representativenessof the resultant RMR for that commodity, which is no less than 78%for any of the commodities analyzed. Importantly, this coverage refersonly to the scope described in the section on A small numberof commoditiesrequired broader assumptions and (or) adjustments in our methodologyin order to calculate a representative RMR due to either lack of granulardata ,unconventional mining or processing methods , extractionmethods for which RMR is not applicable , and(or) decoupled mining and processing operations . Our methodology was adjusted as follows.21Unlike conventionallarge-scale mining operations, artisanal and small-scale mining (ASM)is typically conducted by individual miners on enriched placer depositsthat can be easily exploited with limited mechanized equipment. ASMoperations contribute a sizable portion of the annual tantalum, tin,and tungsten global supply. However, the lack of reliable data onthe production and mined material grades and tonnages makes directquantification of the RMR for artisanal operations very difficult.Thus, we calculate the RMR at the country-level and assume that, becauseof the nature of ASM operations, only ore is extracted and thereforeno additional waste is associated with the mining operation . In the absence of reported ore grades,we assumed average grades of 0.5%W, 1% Sn, or 0.164% Ta based on publishedstudies of artisanal operations exploiting placer and alluvial depositsin Africa.22 and exclude ferrosiliconas well as other forms of silicon for industrial uses  in our calculation. While our single-point silicon estimatedoes not offer the same granularity in data as the other commoditiesin our study, we believe it serves as a useful comparison againstprevious studies that use single-point estimates for all commoditiesstudied.Leadingglobal silicon metal producers arevertically integrated multinational operations that typically processraw material from multiple sources at multiple locations resultingin a data gap between raw material (quartzite) production and siliconmetal extraction. Because of the lack of data availability at moregranular levels than the multinational company level, we calculatethe RMR at the global level for production of silicon metal from high-purity quartzite feedstock based on the ecoinvent LCIrecovery profile,Approximately 80% of globalprimary vanadiumis derived as a coproduct from vanadiferous titanomagnetite ores,recovered from vanadium-rich steel slags (“vanadium slags”)produced during steelmaking. Although steelmaking operations are typicallydecoupled from the mining/ore source, to calculate a representativeRMR at the steelmaking plant-level where vanadium recovery takes place,we treat mining and steelmaking as joint operations with the vanadiumslag representing the “concentrate” stage of a conventionalmining and beneficiation operation.Galliumis extracted as a byproduct duringthe processing of bauxite and zinc ores, and as a result gallium recoveryat the smelter is typically decoupled from the mined ore source. Furthermore,gallium producers typically depend on imported feedstock for galliumextraction. Thus, we calculated the RMR at the country-level onlyfor countries that recover gallium, using trade data to determinethe origin of the ores, and calculate a “gallium ore”composition as a proportionally weighted blend of domestic and importedore based on the country of origin.13 Similarly,magnesium metal is mainly produced from hard-rock sources , with magnesium metal from brines being sourced onlyfrom Israel and the United States, which are estimated to have accountedfor less than 10% of global primary magnesium production in 2018.15 Nevertheless, RMR results for both lithium andmagnesium metal should only be interpreted as being representativeof hard-rock sources.As previouslynoted, nonhard rock sources suchas brines are excluded from the RMR calculation. This has implicationsfor lithium and magnesium metal. In recent years, Australia’sproduction of lithium from hard rock sources, namely spodumene, hasincreased markedly. As such, brine production accounted for roughly30% of total lithium production in 2018 but was as high as 55% onlya few years prior in 2015.31) and vary minimally across operations. An overall global R average of 90% was thus used for each mineral commodity,except when specific information was available. Details are providedin the Supporting Information (Table S2).To obtainthe “ultimate”amount of metal produced, a refinery recovery rate was utilized. Includingoperation-level refinery recovery rates, while theoretically possible,is quite complex given that mineral concentrates are shipped globallyto different smelters and refineries and one would need to trace theflows of the commodities from the mines to the appropriate smelterand (or) refinery. For some commodities, this is not possible as thetrade data are not sufficiently detailed. It is also unnecessary becausethe recovery rates of these downstream operations are relatively high.Note that 32 A uniform unit price was used for each commodityexcept for certain lithium, tantalum, and vanadium operations forwhich uniform prices would not provide an accurate representationof revenue shares and for which commodity-specific revenues were reportedby the companies. This was necessary for operations that produce multiplegrades of concentrate .Details are provided in the Supporting Information (Table S3).Given that most operations producemore than a single commodity, the burdens  were allocated to an individual commoditybased on its revenue share, which was estimated as the product ofthe mine production and realized unit price relative to the revenuefrom all commodities. Unit prices were obtained from the USGS.33 Using economicallocation thus allows for the appropriate allocation of burdens forcoproduct or byproduct metals, which provide a moderate to limitedrevenue contribution to most mining operations.34 Additionally, mineral commodities that occur but are notrecovered receive no burden allocation. Again, this is important formany byproducts  that may be extracted with the oresbut not always recovered.35 If these byproductsdo become economic to recover at a later date, then the RMR may needto be adjusted to account for the new revenue streams that are generatedfrom their recovery. This would be similar to the reprocessing ofmine tailings, with additional allocations needed to account for anymineral commodities that were previously not recovered. A methodologicalquestion remains as to when to allocate the burdens: the year theore was mined or the year the tailings were retreated. As previouslynoted, tailings retreatments were excluded from this analysis, effectivelysuggesting that the allocations belong to the year the ore was mined.Other analysts may elect to allocate the burdens differently.This economic allocation is one of the most widelyrecommended baseline methods in most life-cycle assessment (LCA) allocationsituations and its appropriateness stems from the rationale that economicvalue drives actions.6 forgold , with RMRsfor individual operations ranging by 8 orders of magnitude, from 1.5to 2.2 × 108  (Table S5).Precious metals, led by gold, make up the upper end of this rangewith individual RMRs ranging between 1.6 × 103 and2.2 × 108, whereas the ferrous and nonferrous metalsgenerally plot at the lower end, with RMRs ranging between 1.5 and5.2 × 104. While iron has one of the lowest globalRMR values of the commodities analyzed in this analysis (∼101), it has the largest attributable total quantity of ore minedand waste rock removed at approximately 12.9 billion metric tons afteradjusting for global coverage . This is due to large quantities of iron ore mined (over1 billion metric tons per year). In contrast, the global mine productionof gold is quite small (∼3 thousand metric tons). However,because gold has the highest global RMR, it also has a very high attributabletotal amount of ore mined and waste rock removed at approximately9.1 billion metric tons (after adjusting for coverage), third onlyto iron ore and copper (9.4 billion metric tons). Indeed, the totalattributable quantity of ore mined and waste rock removed, after adjustmentsfor coverage, for these three commodities represents 83.4% of allthe attributable ore mined and waste rock removed from the entireset of 25 mineral commodities examined .RMRs were calculated for each commodity bothfor individual operationsas well as the global level 1. GlobalTable S5). For example, RMRs forcopper range from 2.3 to 1.7 × 104, with 90% of globalcopper production having RMRs of 1.5 × 103 or less. While several factors contributeto the wide range, the results suggest that operation size, as measuredby their share of total global production, and the geographic locationare not significant determining factors. For example, for the 431copper operations included in our analysis, small producers  and large producers occur across the entire RMR spectrum (3). In contrast, factors suchasthe revenue allocation for individual operations that produce morethan one commodity can affect the RMR in that the burden of wastesassociated with an individual operation can be proportionally distributedacross the commodities resulting in lower RMRs for all commodities. Much of the variabilitybetween commodities can be explained by the differences in ore grade,which in turn relate to differences in crustal abundance. For example,aluminum has a global RMR of 7.1, is mined from bauxite with an averageore grade of 25.6% Al, and constitutes 11.4% of continental crust.Another important variablethat affects the RMR is revenue share.For example, silver is often recovered as a byproduct of lead–zinc,gold, or copper; because the waste and losses associated with miningthese metals are distributed over several commodities, silver hasa lower RMR than if no other commodities were recovered from the sameoperations. The effect of byproduct recovery is that an operationcan produce a commodity with the same RMR at a much lower ore gradein comparison to a facility mining the same commodity as a primaryproduct. In Mining method (surface or underground)and material type (hardrock or unconsolidated sediment) are also important factors that determineRMRs because of the different amount of waste material that must beremoved. For example, even with the same ore grade, an undergroundmine with minimal waste rock removal would have a lower RMR than anopen pit mine with an average stripping ratio of 2 tons of waste removedfor every ton of ore. Similarly, unconsolidated sediment, such asalluvial tin and placer gold deposits, can be mined with no overburdenstripping or waste removal, compared to hard rock open pit mines withsimilar grades.38 using a bootstrap forest modelwith 100 decisiontrees were used to determine which factors exert the strongest effecton the RMR. The contribution of each factor to the RMR is presentedas a percentage in Table S8 and Figure S33. Overall, ore grade is the most influential variable controllingthe RMR , followed by revenueshare (16.9%), waste to rock ratio (5.4%), refinery recovery rate(4.9%), and concentrator recovery rate (4.0%). Notably, the RMR foreach commodity may be strongly controlled by one or more variables.For example, bauxite ore grades occupy a relatively narrow range,therefore waste to ore ratio explains the variability in the RMR,whereas revenue share is the primary factor determining the RMR forsilver.To confirm these findings, predictor screeningtests9 that were based solelyon an “average” ore grade  anda constant strip ratio of 2. The RMRs presented do, however, indicateconsiderable variation for the RMR within commodities that was previouslynot described. Indeed, because these results show that the variabilityin the RMR for an individual commodity can span several orders ofmagnitude, one should rely on “average” ore grades andother generalized parameters only when more specific data are notavailable.Given the strong dependency on ore grades, the resultsof thiswork are generally comparable  toprevious studies on ore-TMRImportantly, ore grades and the amount of waste rockremoved  can vary notablythroughout the life of the mine. Because this analysis is a snapshotof a single year it includes a mix of mines at various stages of theirlife. As such, biases due to factors that are age-of-mine dependentare assumed to be minimal, especially for mineral commodities witha large number of mines included in the assessment.40 recognized that the amount of reserves of metals reflects theirabundance in Earth’s crust. Skinner41 expanded this analysis to illustrate the relationship between crustalabundance and mine production, as well as the relationship betweenore grade and energy.The correlationsbetween ore grade, production, reserves, price, and crustal abundancehave been the focus of much research. McKelvey37 This correlationreflects the dependence of RMRs on ore grade . Contextualizing mined material use in terms of the rockmined also helps educate the general public and policymakers aboutthe material intensity and the scale of activity involved in supplyingthe materials and products required for everyday life and the entireeconomy .48 there are other factorsthat need to be taken into consideration. For example, undergroundmines typically have lower RMRs but also require energy for ventilationand temperature control that surface mines do not. Similarly, theproximity to and type of transportation and energy used by a miningoperation may increase or decrease GHG emissions.A manufacturing company that utilizes these mineral commoditiesin their products or processes may use the RMR to inform purchasingdecisions. It is important to remember, however, that the RMR is onlyone component of the environmental burdens associated with a miningoperation. Although average RMRs (or TMRs) may be correlated withthe energy needed for transportation and comminution of mined material,and therefore generally correlated to the associated greenhouse gas(GHG) emissions,Furthermore,the lowest RMR may not necessarily be correlated tolower overall environmental burdens. As noted in the 49 the surplus ore method,50 or other similar methods51 that assumea cumulative relationship between grade and tonnage extracted. Resourcedepletion indicators require assumptions about the likelihood of futuremineral resource discoveries, the quantities of undiscovered in situresources, and the development of extraction technology. In contrast,the RMR calculation presented here represents as closely as possiblethe actual quantities of materials extracted. The RMR should thereforebe thought of as a neutral indicator that on its own does not implyany positive or negative consequences, nor require immediate interventionsor policy changes. Because RMRs provided here represent a snapshotin time, it will be important to review, update, and enhance the underlyingdata as changes in ore grades ,prices , and other factors are expected. Nevertheless,major changes in the RMR parameters across all operations of any mineralcommodity are unlikely in the short term and these results are believedto be representative of the contemporary situation.The RMR is also not equivalent to the crustal scarcityindicator,


Hearing-aid use may reduce risk of dementia, but cognitive impairment makes use more challenging. An observed association between reduced hearing-aid use and incident dementia could reflect either or both of these causal paths. The objective was to examine the effects of each path while minimising contamination between paths.n = 72,180) used multivariable logistic regression to model the likelihood of incident dementia 3.5–5 years post hearing-aid fitting for patients free of dementia and mild cognitive impairment (MCI). Analysis 2  modelled the likelihood of being a persistent hearing-aid user at 3 years 2 months after fitting, contrasting subgroups by level of cognitive function at the time of fitting. Analysis time windows were optimized relative to dataset constraints. Models were controlled for available relevant predictors.Health records data from 380,794 Veterans who obtained hearing aids from the US Veterans Affairs healthcare system were analysed. Analysis 1 (The adjusted OR for incident dementia was 0.73 (95% CI 0.66–0.81) for persistent (versus non-persistent) hearing-aid users. The adjusted OR for hearing-aid use persistence was 0.46 (95% CI 0.43–0.48) in those with pre-existing dementia (versus those remaining free of MCI and dementia).Substantial independent associations are observed in both directions, suggesting that hearing-aid use decreases risk of dementia and that better cognitive function predisposes towards persistent use. Research studying protective effects of hearing-aid use against dementia needs to account for cognitive status. Clinically, hearing devices and hearing care processes must be accessible and usable for all, regardless of their cognitive status. Hearing-aid use shows a protective effect against dementia, but cognitive impairment hastens device disuse.Research studies targeting a protective effect must account for both pathways.To achieve a protective effect, hearing aids need to be usable by people with cognitive impairment.Modifiable risk factors for dementia include untreated mid-life hearing loss , and it The primary treatment for hearing loss is use of hearing aids. One may hypothesise that treatment with hearing aids will alleviate or decelerate cognitive decline , by counteracting one or more of the above mechanisms.Meanwhile, since cognitive impairment is associated with difficulty in maintaining instrumental activities of daily living , it is aBoth longitudinal and cross-sectional quantitative studies have sought to test the existence of the forward path , with reTwo qualitative studies , 18 haveIn this paper, we attempt to separately estimate the magnitude of the effects of the two potential causal paths. Specifically, using data from Veterans Affairs (VA) electronic health records (EHR) of Veterans who had received hearing aids through the VA system, we test the following hypotheses:Hypothesis 1: Persistent hearing-aid use in cognitively intact Veterans aged 60+ years will be longitudinally associated with reduced risk of incident dementia,Hypothesis 2: Pre-existing dementia in Veterans aged 60+ years will be longitudinally associated with reduced hearing-aid use persistence.This work was approved by the Institutional Review Board and the Research and Development Committee of the VA Portland Health Care System (Study #03566), Data Access Request Tracker (tracking number 2014-11-066-D-A04) and VA Patient Care Services.N = 731,213). The following data were available: all diagnostic  and procedural codes for the period 1 January 2007 (or earliest occurrence thereafter) until 31 December 2017; hearing-aid order data between 1 April 2012 and 31 October 2014; and hearing-aid battery order data for 1 April 2012 to 31 December 2017.Data were obtained from the VA EHR system. Within the VA healthcare system, eligible Veterans are provided with hearing aids and batteries (as needed on request) free of charge, each of which are documented in the EHR system. As described previously , the bacn = 380,794. Of these, 98.9% were male.Patients meeting the following criteria were included: (i) surviving until 31 December 2017; (ii) a single hearing-aid order and hearing-aid fitting, between 1 April 2012 and 31 October 2014, with at most 180 days between order date and fitting date; (iii) ≥60 years of age at time of hearing-aid fitting and (iv) audiometric data in the EHR. After applying these criteria, the initial sample size was This initial sample was filtered by additional temporal and diagnostic criteria to extract subgroups of patients for the specific purposes of testing the above hypotheses 1 and 2 in analyses 1 and 2, respectively see .The purpose of this analysis is to examine the forward path (hearing-aid use → cognitive function), corresponding to hypothesis 1. The simplest approach would be to model the likelihood of incident dementia in a specified time interval post hearing-aid fitting in those who were dementia-free at the time of hearing-aid fitting. However, since the absence of a dementia diagnosis does not equate to the absence of cognitive impairment, and because hypothesis 2 states that cognitive impairment may itself result in discontinued use of hearing aids, we took precautions to insulate this analysis from effects of the reverse path (cognitive function → hearing-aid use). This was done by including only patients free of diagnoses of either dementia  window, the length of the incident dementia window and the available Incident dementia: Incident dementia was recorded if at least one diagnosis from the ICD-10 codeset  occurredCovariates: Binary variables were constructed for the presence of each of the following dementia risk factors, based on diagnoses recorded up to 3.5 years post hearing-aid fitting: obesity, stroke, diabetes, depression, bipolar disorder and hypertension. See t if they have ordered a pack of batteries within the 18-month period leading up to t. VA provides enough batteries in each pack for 6 months of full-time use; hence, ‘persistence’ corresponds roughly to continued use at several hours per day.A binary proxy variable indicating whether hearing-aid use remained persistent at 3.5 years post hearing-aid fitting was determined for each patient based on their history of hearing-aid battery orders, according to our previously published derivation . In brieLogistic regression was used to model the likelihood of incident dementia 3.5 to 5 years post hearing-aid fitting. The analysis controlled for hearing-aid use persistence at 3.5 years post fitting (binary), age (to second order) and the covariates listed above.The purpose of this analysis is to examine the reverse path (cognitive function → hearing-aid use), corresponding to hypothesis 2. Since hypothesis 1 states that hearing-aid use itself may affect cognitive status, we took precautions to insulate this analysis from effects of the forward path (hearing-aid use → cognitive function). This was done by including only those patients whose cognitive status (as indexed by diagnostic codes) placed them at the high or low end of the spectrum, and whose status remained unchanged from hearing-aid fitting onwards. The sample therefore comprisedN = 5,838) of patients whose EHRs included at least one diagnosis of dementia  of patients whose EHRs contained no diagnoses of dementia or MCI , and additional variables known to be strongly associated with hearing-aid use persistence : MultimoFor both analyses, the raw data and adjusted model estimates of the primary outcome were plotted by the predictor of interest and by patient age group (decade) to facilitate interpretation.P-values for predictors in the logistic regression model of analysis 1. As shown in P-values for predictors in the logistic regression model of analysis 2. As shown in The results of this study corroborate previous evidence supportive of both hypothesis 1 and 2, taking an approach which attempts to avoid some of the shortcomings of earlier studies. In particular, we have taken steps to minimise contamination between the hypothesised forward and reverse causal paths and have examined both pathways using the same dataset.et al. [Consistent with previous findings, we found that patients over 60 years of age without cognitive impairment at the time of hearing-aid fitting, who remained persistent hearing-aid users, had 27% reduced odds of receiving a dementia diagnosis 3.5–5 years after hearing-aid fitting than patients who did not persist in hearing-aid use. Our OR of 0.73 (CI 0.66–0.81) is broadly in line with the hazard ratio of 0.82 (CI 0.76–0.89) found by Mahmoudi et al.  in a larThis study provides (to the authors’ knowledge) the first quantitative evidence that the diagnosis of dementia is associated with subsequent lower persistence of hearing-aid use. Patients over 60 years of age with a dementia diagnosis prior to hearing-aid fitting had 54% reduced odds of being persistent hearing-aid users (corresponding to approximately 15 percentage points in each age stratum) compared to those remaining free of MCI and dementia throughout the study time window. This may be due to reduced abilities to perform instrumental activities .The two patient groups in analysis 2 differed on several baseline characteristics . The preThe strengths of this study include a large longitudinal sample, key hearing data and access to information on a wide range of relevant covariates. There are also some limitations.Our efforts to minimise contamination between the hypothesised causal paths are necessarily imperfect, and demand scrutiny. We first consider the estimation of the reverse path , where the contamination risks differ for the two patient subgroups. For the prevalent-dementia group, contamination from the forward path would have to take the form of persistent hearing-aid use lifting some patients out of dementia. This requires that persistent hearing-aid use reverses the slope of cognitive function over time, which seems highly unlikely. For the high-functioning group, the possible contamination would be that some patients remain high functioning only because they persist with hearing-aid use, i.e. a flattening of the slope of cognitive function versus time. In order to have any noticeable influence on the outcome of analysis 2, the flattening effect would have to be much larger than has been estimated in previous research . Thus, wThe time window for dementia incidence in analysis 1 was only 18 months. While this is short in comparison to typical rates of cognitive decline (and thus less reliable for detecting incidence), this weakness is at least to some extent compensated by the relatively large sample size.The Veteran population is not representative of the general population with respect to health, demographic status or psychosocial characteristics . Hence, One might contend that the care processes in the VA Healthcare System only represent one approach amongst many, and that the effects seen in analysis 2 are dependent on specific aspects of the VA system. While there is theoretical merit to this argument, VA care processes vary considerably across a wide network of locations and settings, and are not overly standardised. Furthermore, previous work with the same patient sample  indicateDue to the nature of our dataset, we had to evaluate hearing-aid use persistence at slightly different timepoints in the two analyses, introducing an arbitrary bias. However, analyses on a superset of the present dataset show that hearing-aid use persistence is very stable from about 2 years after hearing-aid fitting onwards .While the large, longitudinal sample from an EHR is a strength of this study, utilising EHR data for research has some limitations. Covariate selection was limited to variables for which data were available and reliable. For example, analyses did not adjust for socioeconomic status (e.g. education) and history of smoking, both of which are risk factors for dementia  and may Finally, by requiring survival to 31 December 2017, we could also have introduced some distortion of the observed effects, since dementia is independently associated with excess mortality . HoweverThis is the first study to combine longitudinal data regarding dementia diagnoses with continuous assessment of hearing-aid use in a large patient sample. The results are consistent with the hypothesis that untreated hearing problems increase risk of dementia and considering the potential underlying neurological mechanisms it would be surprising if we had found otherwise. Moreover, and not unexpectedly, cognitive impairment appears to be a factor in the discontinuation of hearing-aid use. This implies that lack of or inconsistent hearing-aid use could promote cognitive decline both in those with, and those without, dementia, raising the prospect of a vicious cycle of untreated hearing problems and cognitive decline. Future research studies investigating this must be designed in such a way as to account for the effects of cognitive decline itself on hearing-aid use persistence. In a clinical context, any protective effect of hearing-aid use against dementia will not be adequately achieved unless devices and care processes are usable by and accessible to the target population. To encourage and promote persistent hearing-aid use, more dementia-friendly devices and care processes are needed.aa-22-0569-File002_afac266Click here for additional data file.


Globally, more than 1.5 billion people experience some degree of hearing loss. Of these, an estimated 432 million adults and 34 million children suffer from disabling hearing loss, that is, hearing loss of moderate or higher severity in the better hearing ear [Personalized medicine (PM) refers to the tailoring of medical treatment to the individual characteristics of each patient. In the last approx. 10 years, PM has shifted the traditional “one size/drug fits all” approach into a more stratified therapeutic strategy which includes prevention, diagnostics, therapy/treatment, and rehabilitation . In the This editorial will delineate the approach of PM in the field of otology. Based on the development of better radiological diagnostics and the audiological assessment of hearing disorders in recent years, the approach of PM has become an integral part of modern otological treatment of patients. The evolution of data management in our field gives us information for more precise interventions to treat hearing disorders. Optimized diagnostics such as e-BERA and OAEs has modified the approach to treat patients with hearing disorders significantly. Due to more precise audiological diagnosis, we are able to treat patients sooner in their lives and, hence, elevate the outcomes in hearing rehabilitation.The development of modern radiologic diagnostics with CT and MRI and digital volume tomography has enhanced the quality of surgical treatment approaches in many ways.Over the years, all these developments have enabled hearing implant companies to tailor the product to the needs of the treated subjects ,3,4,5,6.We are all similar, of course, but we are also different in many aspects. The approach of personalized medicine in otology does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease, or in their response to a specific treatment. PM may be considered an extension of traditional approaches to understanding, treating, as well as rehabilitating a disease. Equipped with pre-, intra-, and post-operative tools that are more precise, physicians can select a therapy or treatment protocol based on a patient’s hearing or anatomical profile that may not only minimize harmful side effects and ensure a more successful outcome, but in turn also improve the patient’s quality of life as well as that of their families and peers. Medical advances are significantly increasing the amount of available disease-relevant patient data and treatment options. Some of the challenges lie in standardizing, securing, and managing this complex data. The standardization process needs to be secure and reliable since it deals with sensitive patient data. As hearing implant technology advances at an exponential rate, the size of both internal and external devices is expected to be miniaturized. In addition, advances in directional microphone technology will improve the design of future devices . In comb


Despite its clinical usefulness, the use of tetracycline antibiotics (TCs) in children has historically been limited because of the risk of permanent tooth discoloration and enamel deformity, although age restrictions have varied across countries . We explored whether the incidence of dental abnormalities in Korean children with a history of TCs use differed by age. Furthermore, the relative risk compared to the TCs non-exposed group was calculated.From 2002 to 2015, 1 million standard sample subjects data was provided from National Health Insurance Service in Korea. Children younger than 18 years were included and divided into groups A (0-7 years), B (8-12 years), and C (13-17 years). Subjects in 2002 were excluded for wash-out, as were those diagnosed with dental abnormalities within 6 months after TCs prescription. For comparison, 1:4 matching between the TCs exposure and non-exposure groups was performed according to age and gender.Among 14,831 individuals included as study subjects (487 (3%) in group A; 1,695 (11%) in group B; and 12,649 (85%) in group C), 201 (1.4%) were diagnosed with dental abnormalities. The 5-year cumulative incidence of dental abnormalities after exposure to TCs in the group A was 4.7%, which was significantly higher than that of the control group C , but that of group B was 1.3% and not significantly different from that of group C. In the risk analysis of dental abnormalities according to exposure of TCs, there was no significant difference .Korean children aged 0-7 years who were exposed to TCs had a higher cumulative incidence and relative risk of dental deformities compared to the 13-17-year-old group but not the 8-12-year-old group. No significant increase in dental abnormalities was observed with TCs exposure among pediatric age groups.All Authors: No reported disclosures.


It was gradually accepted that endoscopic fragment biopsy (EFB) diagnosis cannot accurately guarantee the absence of higher-grade neoplasms within the lesion of the digestive tract. There are no well-established predictors for histopathologically upgrade discrepancies between EFB diagnosing colorectal low-grade intraepithelial neoplasia (LGIN) and endoscopic resection (ER) specimens.  A total of 918 colorectal LGINs was histopathologically diagnosed by EFB, including 162 cases with upgrade discrepancy and 756 concordant cases. We compared clinicopathological data of EFB and ER specimens between these two groups. Multivariate analysis was performed to identify predictors for this upgrade histopathology. p < 0.001), insufficient EFB number , maximum diameter ≥ 1.0 cm , lobulated shape , erythema , erosion , surface unevenness , and distal location of the target adenoma  were associated with the histologically upgrade discrepancies.  The predominant upgrade discrepancy of LGINs diagnosed by EFB was upgrades to high-grade dysplasia , followed by upgrades to intramucosal carcinoma , submucosal adenocarcinoma , and advanced adenocarcinoma . NSAID history (OR 4.83; 95% CI, 2.27-10.27;  NSAID history, insufficient EFB number, adenoma size and location, and abnormal macroscopic patterns are potential predictors for upgrade histopathology of LGINs diagnosed by EFBs. The standardization of EFB number and advanced imaging techniques could minimize the risk of neglecting the potential of this upgrade histopathology. Among all individuals worldwide in 2018, colorectal cancer (CRC) has become the third most commonly diagnosed cancer for incidence and the second leading cause of cancer death . As the For the intraepithelial neoplasia in the digestive tract, it has been reported that there are some histopathological discrepancies between endoscopic forceps biopsy (EFB) and pathological outcomes of ER specimens, such as superficial esophageal squamous neoplasm, gastric epithelial neoplasia, and colorectal polyps –10, wherThis retrospective study was based on standard documentation of patients undergoing EMR and ESD in the First Affiliated Hospital of Nanchang University from January 1, 2013, to September 9, 2018.The participants are patients who were diagnosed with by EFBs demonstrating colorectal adenoma of LGIN. The primary exclusion criteria were endoscopic intolerance with severe cardiopulmonary dysfunction, coagulation disorders, low healing capacity with diabetes mellitus, other severe complications, and refusal to receive endoscopy treatment. Identified by postoperative pathology, patients diagnosed with the colorectal adenomas of HGIN or adenocarcinoma were selected as the case group . Patients still diagnosed with colorectal adenoma of LGIN were selected as the control group . Patients with incomplete data for adenoma characteristics and laboratory examination at baseline were excluded in both two groups. After exclusion, 162 cases and 756 controls were identified .We collected patients' characteristics including age, gender, personal medical history of hypertension (HT), and diabetes mellitus (DM), using nonsteroidal anti-inflammatory drug (NSAID), colorectal polyps, CRC, familial adenomatous polyposis (FAP), ulcerative colitis (UC), Crohn's disease (CD), and the number of polyps (single or multiple). We also obtained patients' blood lipid level including triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), and carcinoembryonic antigen (CEA).We established the principle of selecting a target adenoma from one patient. The adenoma with larger size or abnormal macroscopic characteristics was selected as target if there are multiple adenomas in one individual. We also recorded the clinicopathologic data of target adenomas: site , adenoma diameter, Yamada classification (I-II or III-IV), the proportion of laterally spreading tumor (LST), macroscopic patterns , standardization for EFB number, EFB histopathology (tubular or tubulovillous or villous), and postoperative pathology (LGIN or HGIN or adenocarcinoma). Based on the consensus, Yamada classification is our reference for assessing the macroscopic type of targeted adenomas . The defBowel preparation was abstracted on the report forms –16. ConvIn the cases of EMR, we injected a saline solution containing 0.5% methylene blue and 0.1% epinephrine into the mucosa underneath the basal part of colorectal neoplasms to lift the neoplasm. Then, the neoplasm was snared by the elastic band and resected by a blended electrosurgical current. In the cases of ESD, we injected a saline solution containing 0.5% methylene blue and 0.1% epinephrine in the circumferential edge of the targeted neoplasm into the submucosal space to lift the neoplasm. A circumferential incision was carefully executed by using a needle knife  or a needle knife plus an insulated-tip knife  with subsequent continuous submucosal dissection. For prophylaxis of delayed bleeding, hemostatic forceps  and argon plasma coagulation (APC) were taken to coagulate visible active bleeding vessels in the resected surface of EMR and ESD. For the closure of the wound, a titanium clip and rope were utilized depending on the condition of the wound undergoing EMR and ESD.The diagnosis of EFBs and ER specimens was assessed and determined by two independent expert gastrointestinal pathologists.t-test and expressed as means ± SD. Age, maximum diameters of adenoma, and blood lipid level were not distributed normally and were expressed as median and interquartile range (IQR) of 25th and 75th percentiles. The Mann–Whitney U test was used for statistical analysis of these data. The significance of difference for categorical variables was assessed by chi-square tests or Fisher's exact tests, which were presented as the odds ratio (OR) and 95% confidence interval (CI). Statistical significance was determined at an α level of 0.05 by utilizing two-sided tests. Multiple logistic regression was used to identify the significant factors for the phenomenon of this inconsistent pathology.Continuous variables were calculated by using the Student p < 0.05 in the univariate analysis were selected as potential risk factors in the multivariate forward stepwise logistic regression analysis. All statistical analyses were performed using the Statistical Package for Social Science software suite .Post hoc testing was used to measure the predictive significance of the EFB diagnosis and macroscopic type. Multiple variables with Baseline characteristics of 918 enrolled patients with LGIN diagnosed by EFBs are summarized in p = 0.012), the proportion of patients with NSAID , insufficient EFB number , maximum diameter of the target adenoma , lobulated pattern , erythema , erosion , surface unevenness , and distal location of the target adenoma  were significantly greater in histopathologically upgrade group. TC  and LDL  were significantly lower in the upgrade group. There was no significant difference in the proportion of patients with DM, colorectal polyps, FAP, and CRC history between the groups. Gender, age, TC, HDL, the proportion of Yamada III+IV classification, LSTs, and multiple colorectal polyps did not differ between two groups.Clinicopathologic characteristics of 918 patients are presented in p < 0.001) was observed between two groups. Based on post hoc testing, the value of Cramer's V in EFB diagnosis is 0.127 (p = 0.001), which indicated a small magnitude of effect size. In the histopathologically upgrade group, the adjusted standardized residual of tubular, tubulovillous, and villous EFB diagnosis were -3.3, +1.9, and +3.2, respectively.The significant difference in EFB result , lack of standardization of EFB number , ≥1.0 cm maximum diameter of the target adenoma , lobulated shape , erythema , erosion , surface unevenness , and distal location of the target adenoma  were significantly associated with the histologically upgrade discrepancies  implied a beneficial and chemopreventive effect of NSAID use on the presence of HRAP and recurrence of colorectal adenomas –27. A muIt is meaningful for clinicians to take the fewest number of EFB, while maintaining histopathologic accuracy. We recommend a standardization that EFB number should be obtained at least the integer part of the maximum diameter of a target adenoma, which is valuable experience from the clinical practice in our hospital . The incThere are a series of evidence showing a more distal distribution of colorectal adenomas and advanced adenomas in Asia compared with the U.S., which is identical to our results –38. AddiThe purpose of our study is to figure out high-risk colorectal adenoma and early cancer in time and achieve early accurate diagnosis. After identifying these predictors, we summarized meaningful strategies to minimize the risk of neglecting these upgrade discrepancies. First, the experience in our institution elucidates that multilayered biopsies should be clamped apically to basally  for high-risk adenomas in order to avoid the neglection of malignant lesions. Second, advanced imaging including narrow-band imaging (NBI), magnifying chromoendoscopy (MCE), confocal laser endomicroscopy (CLE), and blue laser imaging (BLI) is recommended in predicting deep submucosal invasive carcinoma and promoting early diagnosis of T1 CRC dependent on their precise evaluation of the surface pattern, pit pattern, and capillary vessels –45. But The nature limitations of retrospective studies are inevitable in our study. And the pathologic diagnosis of EFB and ER specimens was assessed by different pathologists which probably leads to interobserver variability . BesidesOur results imply that EFB diagnosis of colorectal adenomas with LGINs cannot accurately guarantee the absence of higher-grade neoplasms or carcinoma foci within the lesion. NSAID history, insufficient EFB number, tumor size and location, and abnormal macroscopic patterns are potential predictors for upgrade histopathology of LGINs diagnosed by EFBs. And upgrade histopathology would be far more likely if more risk factors simultaneously existed. Improving the standardization and skills of EFB, advanced imaging techniques could contribute to the accurate detection and diagnosis of colorectal lesions.


Hypergranulation is a common complication of wound healing that dermatologists encounter and is characterized by excess granulation tissue, which results in delayed healing and reepithelialization. Though many treatment options have been presented in the literature, less invasive and irritating treatment regimens are often preferred in the pediatric population. Here we present a case of a 14-year-old female with hypergranulation tissue (HGT) of the scalp that was successfully treated with topical corticosteroids (TCS). Additionally, a literature review was conducted to determine the prevalence of topical corticosteroid use for HGT in the pediatric population. Although not first line, TCS should be considered as a non-invasive and painless treatment for HGT in the pediatric population. Hypergranulation is characterized by excess granulation tissue, which results in delayed wound healing and reepithelialization. Hypergranulation tissue (HGT) frequently presents as friable red tissue that extends above and beyond the original surface of the wound . VariousA 14-year-old previously healthy female presented to the clinic accompanied by her mother for complaints of a scalp burn. Six weeks prior, the patient had dyed her hair with an expired hair product resulting in scalp pain and irritation. She visited the emergency department (ED) where she presented with an erythematous, scaly scalp erosion. She was prescribed cephalexin and silver sulfadiazine every other day and then daily for 10 days. Two weeks after initially healing, she developed worsening pain, scaling, and discharge. She returned to the ED and was given a 10-day course of clindamycin 300 mg four times daily for possible infection. She was then referred to pediatric dermatology.During clinic follow up, the patient stated that the lesion had not adequately improved despite treatment. On examination, a 3.5 x 3.0 cm red, friable eroded plaque was noted on the vertex scalp Figure . She wasGiven the characteristic physical examination and clinical history, the diagnosis of HGT was highly suspected over less likely differential diagnoses of pyogenic granuloma and a cutaneous malignancy. The patient's parent deferred a biopsy in place of empiric treatment and a follow-up six weeks later to reassess clinical progress. In cases where the diagnosis is unclear or empiric treatment fails, however, a biopsy should be performed to confirm the diagnosis. If there was clinical suspicion of a potentially harmful diagnosis, such as malignancy or infection, a biopsy would have been recommended. Additionally, if the patient was not clinically improving at her six-week follow up, biopsy would be the next step. HGT is characterized by overgrowth of fibroblasts and endothelial cells that impedes healing by preventing the migration of epithelial cells across the wound. It is associated with an increased risk of infection . Scalp sTraditional treatments for HGT include silver nitrate, TCS, surgical debridement, and pulsed dye laser . Less coWhen treating the pediatric population, great consideration should be made to select therapies that are effective while also causing little discomfort. This principle is followed in other aspects of pediatric dermatology, such as in the treatment of molluscum contagiosum. While curettage of molluscum contagiosum lesions is an effective treatment method, this can cause significant fear and pain in pediatric patients, and is therefore avoided . TherapiIn conclusion, high potency TCS are an effective treatment for HGT and should be considered as a treatment option in the pediatric population. Special care should be taken when treating children to avoid discomfort while maximizing results. Unlike other standard treatments, TCS are painless and non-invasive, making them a more palatable option for children and their caretakers. This case report adds to the literature evidence of resolution of HGT tissue after use of clobetasol 0.05% ointment, without the occurrence of patient discomfort. Further studies may be warranted to compare long term outcomes and comparison of cosmetic results with other, more traditional treatment modalities.


COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, COL9A3) and non-collagen genes . The most frequent type of Stickler syndrome (COL2A1) is characterized by a rather mild high-frequency sensorineural hearing loss in about half of the patients. COL11A1- and COL11A2-related Stickler syndrome results in more frequent hearing loss, being moderate and involving all frequencies. Hearing loss in the rarer types of Stickler syndrome depends on the gene expression in the cochlea, with moderate to severe downsloping hearing loss for Stickler syndrome caused by biallelic type IX collagen gene mutations and none or mild hearing loss for the non-collagen genes. Inherent to the orofacial manifestations, middle ear problems and temporary conductive hearing loss, especially at young age, are also prevalent. Consequently, hearing loss should be actively sought for and adequately treated in Stickler syndrome patients given its high prevalence and the concomitant visual impairment in most patients.Stickler syndrome is a connective tissue disorder characterized by ocular, skeletal, orofacial and auditory manifestations. Its main symptoms are high myopia, retinal detachment, joint hypermobility, early osteoarthritis, cleft palate, midfacial hypoplasia, micrognathia and hearing loss. Large phenotypical variability is apparent and partly explained by the underlying genetic heterogeneity, including collagen genes ( Stickler syndrome is named after Gunnar B. Stickler, a German American pediatrician who worked at the Mayo Clinic in Rochester (USA). In 1965, he described a five-generation pedigree with autosomal dominant inheritance of high myopia, retinal detachment resulting in blindness, hypermobility of the joints, abnormal development of the articular surfaces and premature degenerative changes . In the Hearing loss, the topic of this review, has been variably described in Stickler syndrome and the auditory system is probably the least studied in literature. Audiometry was not performed or reported in numerous publications describing the phenotype of Stickler syndrome patients. Based on a systematic literature review, hearing loss occurred in 63% of the patients .COL2A1 gene in 1991 [COL11A1 and COL11A2 gene could also be associated with a Stickler syndrome phenotype [COL2A1), whereas a beaded vitreous anomaly is often associated with type 2 Stickler syndrome . In type 3 Stickler syndrome , no ocular symptoms are observed as Col11a2 is not expressed in the eyes [Eventually, part of the auditory heterogeneity seen in Stickler syndrome was resolved by the discovery of different genes involved in the syndrome. The first mutation in a Stickler syndrome family was found in the  in 1991 . Some yehenotype ,7. In adthe eyes . To our Given the differences in auditory phenotype among the different genes involved in Stickler syndrome, it is important to focus on molecularly confirmed Stickler syndrome patients and distinguish between the different types/genes.COL2A1 and confirms the diagnosis in the vast majority of Stickler syndrome cases. A systematic review showed that 52% of STL1 patients had hearing loss, whether based on history taking or audiometry [STL1 is caused by a heterozygous mutation in diometry , and thediometry . Progresdiometry . ConsequHearing loss in Stickler syndrome is predominantly sensorineural and symmetric. Conductive and mixed hearing loss is observed in only a minority, most of whom are young children, and is predominantly due to middle ear problems, regardless the type of Stickler syndrome ,18. HoweCOL2A1 encodes type II collagen, which is the principal component of articular and hyaline cartilage, and is also present in vitreous and inner ear structures [COL2A1 mRNA in both the inner and outer hair cells, although type II collagen has also been observed in the tectorial membrane of the developing cochlea [ructures . The ear cochlea . STL1 is cochlea . GlycineHearing loss in STL2 and STL3 is very similar and will thus be discussed together. Its prevalence is estimated to be between 69% and 83% . The aveCOL11A1 and COL11A2 mutation spectrum considering hearing. Most heterozygous COL11A1 mutations linked to Stickler syndrome are supposed to result in a dominant-negative effect [COL11A1 mutations resulting in haploinsufficiency have been associated with Stickler syndrome manifestations [COL11A2 mutations. Of interest, biallelic dominant-negative non-glycine COL11A2 substitutions have been described in non-syndromic hearing loss, being prelingual profound deafness [COL11A1 mutations [A genotype-phenotype correlation can be seen in the e effect . Few hetstations , and thestations . The samdeafness . Profounutations .COL11A1 and COL11A2 encode components of type XI collagen, which is widely distributed throughout the body as a regulator of collagen fibrillogenesis in assembly with type II collagen. It is quantitatively present in a rather limited extent though. In addition to its presence in cartilage, essential for skeletal morphogenesis during embryonic development and for articular joint function, it is expressed in other developing structures including the otic vesicle [Col11a1 and Col11a2 may affect hearing due to impaired structure and function of the basilar and tectorial membrane [Col11a2 alleles exhibited a smaller body size, shorter snout and deafness [Col11a2 demonstrated a frequency-independent moderate cochlear loss and confirmed the involvement of the tectorial membrane by showing impaired collagen fibrillar configuration [Col11a1 in mice did not result in significant hearing loss [The genes  vesicle . Col11a1 vesicle ,34, thusmembrane . Mice wideafness . Mice wiguration . Heterozing loss , as in hCOL9A1, COL9A2 and COL9A3, respectively. Their clinical features have been summarized by Nixon et al. [Type 4, 5 and 6 Stickler syndromes  have been attributed to homozygous or compound heterozygous mutations in the type IX collagen genes n et al. . In summFocusing on the auditory features of these recessive types of Stickler syndrome, sensorineural hearing loss was consistently present in all patients. Moreover, analysis of the audiograms showed striking resemblance: a downsloping curve with mild to moderate hearing loss in the lower frequencies to severe and even profound hearing loss in the higher frequencies. However, variability in severity of hearing loss is apparent. The onset of hearing loss, whether congenital or at childhood age, remains unclear. Both failed and uneventful auditory screening at young age has been reported ,39, but The involved genes encode the chains for collagen type IX, which is a fibril-associated collagen with interrupted triple helices (FACIT) protein associating with type II and type XI collagen. Murine studies confirmed the involvement of type IX collagen, in addition to type XI collagen, in maintaining the integrity of collagen fibers in the tectorial membrane . Knock-oMutations in non-collagen genes are also able to cause a Stickler-like phenotype. It concerns genes with similar expression patterns as the involved collagen genes, especially in the ocular and/or skeletal system, and eventually exhibiting additional symptoms. Based on clinical variability, one might consider a Stickler syndrome phenotype in these patients.LRP2 gene. A homozygous LRP2 mutation was found in two siblings with a possible Stickler syndrome diagnosis mainly based on their ocular phenotype, including high myopia, vitreous changes, cataract and esotropia [LRP2 mutations are mainly associated with Donnai-Barrow syndrome and facio-oculo-acoustico-renal syndrome. The gene encodes an endocytic transmembrane receptor, which is strongly expressed in the marginal cells of the stria vascularis. Hearing testing in Lrp2-deficient mice showed a progressive hearing impairment [A first example is the sotropia . Mild jopairment , which mLOXL3 mutations have also been linked to a Stickler syndrome phenotype [LOXL3 mutations seem to mimic the classic Stickler syndrome phenotype most, which might be due to the function of the gene. LOXL3 is a lysyl oxidase gene encoding enzymatic proteins that enable cross-linking of collagen fibers in the extracellular matrix. Tissue-specific ablation of Loxl3 in the inner ear resulted in progressively elevated hearing thresholds for all frequencies [Biallelic henotype ,46. Sevehenotype ,46. Of tquencies . Microscquencies .BMP4 mutation [BMP4 phenotype is associated with variable ocular manifestations, ranging from anophthalmia to stigmata associated with Stickler syndrome such as high myopia, retinal detachment and a congenital vitreous anomaly. Retrognathia and a high-arched palate were also seen in this family, as well as renal dysplasia, the latter being typical for BMP4 mutations but not for Stickler syndrome. Audiograms of the affected members were made available, mainly showing a high-frequency sensorineural hearing loss, more pronounced with older age and more than we would expect from age-related hearing loss alone [BMP4 encodes a growth factor belonging to the TGF-ß superfamily and proved important in the embryonic development of different organ systems, especially ocular development. In the murine inner ear, Bmp4 heterozygous null mice showed elevated hearing thresholds and circling behavior, suggesting inner ear involvement. Based on microscopic analysis, the number of neuronal processes in the murine organ of Corti as well as the number of vestibular stereocilia was significantly reduced [A third example is a family exhibiting a heterozygous disease-causing mutation . The BMPss alone . In this reduced .Hearing loss is a frequent manifestation of Stickler syndrome. It is often not detected until formally tested as the hearing loss associated with the most prevalent type 1 Stickler syndrome is rather mild and only affects the higher frequencies. It can be distinguished from the hearing loss in type 2 and type 3 Stickler syndrome, which is more pronounced and affects all frequencies. The hearing loss can be explained by the involved types of collagen being expressed in the inner ear, mainly in hair cells and the tectorial membrane, and is thus sensorineural. However, conductive hearing loss has also been reported, mainly linked to the orofacial symptoms including cleft palate and midfacial hypoplasia, affecting Eustachian tube function. Hearing in the rarer types of Stickler syndrome depends on the expression of the involved gene in the cochlea. It has been reported in collagen IX gene mutations, but not consistently in the non-collagen genes causing a Stickler syndrome phenotype. In conclusion, hearing loss should be actively sought for and adequately treated in Stickler syndrome patients given its high prevalence and the concomitant visual impairment in most patients.


In the present days it is critical to identify the factors that contribute to the quality of the audiologic care provided. The hearing aid fitting model proposed by the Brazilian Unified Health System (SUS) implies multidisciplinary care. This leads to some relevant and current questions.To evaluate and compare the results of the hearing aid fitting model proposed by the SUS with a more compact and streamlined care.We conducted a prospective longitudinal study with 174 participants randomly assigned to two groups: SUS group and Streamline group. For both groups we assessed key areas related to hearing aid fitting through the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire, in addition to evaluating the results of Speech Recognition Index (SRI) 3 and 9 months after fitting.Both groups had the same improvement related to the speech recognition after nine months of AASI use, and the IOI-HA didn't show any statically significant difference on three and nine months.The two strategies of care did not differ, from the clinical point of view, as regards the hearing aid fitting results obtained upon the evaluation of patients in the short and medium term, thus changes in the current model of care should be considered. Sistema Único de Saúde - SUS), based on the principles of health as a right of the citizen and a duty of the State. SUS aims at providing broad and universal preventive and curative healthcare, by managing and providing decentralized healthcare services, promoting community participation in all levels of public administrationSince 1988, Brazil has been establishing a dynamic and complex public health care system  - University of São Paulo, Bauru Campus. The patients recruited were referred to Audiological Diagnosis at the Auditory Health Division of the Craniofacial Anomalies Rehabilitation Hospital (DSA/HRAC-USP) - Bauru Campus, which is a clinic listed in the high complexity roster of the Public Healthcare System - SUS.The present study was approved by the Ethics in Research Committee of the associated institution (Research Protocol # 327/2008), linked to the CNPq project # 476233/2008-9. All the volunteers received an informative letter and signed the Informed Consent Form, thus consenting with the execution and disclosure of this study and its results, as per resolutions 196/96 and MS/CNS/CNEP n 196/96 of october 10, 1996.•Age of 15 years and older•Unilateral or bilateral sensorineural or mixed hearing loss•With or without previous experience with an ISAD•Current users or potential users of a behind-the-ear hearing aid (ISAD)The initial sample was made up of 174 participants from both genders. The following criteria had to be met for patient enrollment:Individuals with air-conduction-type hearing loss and those with retrocochlear changes and those with disorders associated with the hearing loss  were taken off the study.The participants were randomly assigned to two groups: SUS group .Below, we list the procedures and instruments used to develop this field study.1.Selection of three retroauricular ISADs2.Selection of a proper prescription method3.Speech perception assessment with and without the three ISADs selected by means of specific procedures4.Functional gain assessment by means of a free-field audiometry without ISAD and with the three models of hearing aids selected5.Measurement assessment with the probe microphone (insertion gain) with the three models of hearing aids (ISADs) selected6.Indication and fitting of ISAD, with the best results obtained in the procedures listed above7.Instructions to the patients or guardians about use, handling and care with the fitted hearing aid, as well as the benefits and limitations of the amplification8.Following up at three and nine months after fitting.After the patient entered the clinic, their audiological diagnosis was proposed according to Ordinance SAS/MS nº 587These eight items are prescribed by the SUS-guiding ordinance, besides consultations with other professionals, such as psychologists, social workers and ENT physicians at the hearing aid indication and fitting.Consultation time for this group was not established.In this model, the team was made up only by a speech and hearing therapist (audiologist) and the difference would be only related to the ISAD selection and fitting, following the same proposal during diagnosis stage. The procedures were done by only one audiologist during all the stages and in follow up. In this model, the multidisciplinary team acted only in the cases of hearing loss, those who were not part of the investigation. Moreover, the equipment used in the care of these patients was all located in one single room.1.Selection of the prescription method: NAL-NL12.Selection of only one retroauricular ISAD model from the prescription rule3.Speech perception assessment with and without the single ISAD model selected, by means of specific procedures4.Measurement assessment with a probe microphone (degree of insertion) with the single ISAD model selected5.Instruction to the patients or guardians regarding the use, handling and care concerning the fitted hearing aid, as well as benefits and limitations of the amplification6.Follow up at three and nine months after fitting.The procedures in this group involved:The visit in this group should not take longer than 30 minutes in cases of unilateral hearing loss, and 45 minutes in cases of bilateral hearing loss, for selection and follow up.At three and nine months of follow up we assessed important domains for ISAD fitting for both groups - SUS and Streamline - , and we employed the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire, proposed by Cox et al.The IOI-HA was administered after 3 and 9 months of hearing aid use.The IOI-HA questionnaire analysis was carried out considering the score from each question and the total score obtained by adding the scores from the seven questions. Considering the seven questions, the alternatives correspond to a minimum score of one (1) and maximum of five (5), from left to right. The total score is given by the summation of the points obtained from each one of the seven questions. Thus, the minimum total score was 7, and the maximum was 35 points. A higher score indicated better results in relation to the ISAD fitting.The descriptive analysis of the results was carried out by means of the Stata software, version 10.0. The Chi-square and Mann-Whitney tests were utilized to check whether there were differences between the groups as far as gender is concerned, socioeconomic class, schooling, age, ISO mean of the audiometric thresholds  of the middle ear and Speech Recognition Index (SRI).The Mann-Whitney test was utilized to compare the IOI-HI scores between the groups. The Wilcoxon test was utilized to compare the IOI-HA scores between the three and nine months of ISAD use for both groups.The Wilcoxon test was utilized to check whether there was a difference between the Speech Recognition Index (SRI) in the two models investigated before fitting the hearing aid, and 3 and 9 months afterwards. The differences in SRI results between the two groups were investigated by the Mann-Whitney test.For all the cases we adopted a 5% level of significance.The results from the sociodemographical variables analysis [age range, gender , schooliWe did not find significant differences between the two groups as far as age and gender were concerned  - enabliThe same homogeneity profile was seen for schooling and socioeconomic status in the groups studied. Both in the Streamline as well as in the SUS groups, over 80% of the population belonged to C and D classesAlso, in relation to audiological characteristics found in both groups, there were no statistically significant differences, and most of the participants in both groups had mild hearing loss .As to the results from the IOI-HA questionnaire, for the SUS group, the mean scores for each question were between 4.34 and 4.87 and for the Streamline; the mean score of the participants was between 4.30 and 4.93 at three months . During Insofar as the results from both groups are concerned, we did not find statistically significant differences in the total score from each question  and in the total score of the IOI-HA questionnaire at three  and ninep = 0.3051), in other words, we had no difference in using one or the other strategy in the total results from the questionnaire at three and nine months.What we see in the results is that, at 3 and 9 months, there was no variation between the two groups. At 3 months, both groups were equal in terms of the mean value of the Total in the IOI-HA questionnaire . At 9 months we found a small difference , however non-significant .The This study was done with the goal of comparing the two models of care: the SUS model, with a more compact and streamlined model of care vis-à-vis the individuals’ assessment of speech performance and important fitting domains, such as the use of ISAD, benefit, satisfaction, participation restriction, activities limitation, impact of the hearing loss on others and quality of life. The intent was to assess whether or not it would be possible to maximize care without losing quality.Based on the results obtained, it was possible to notice that the two groups had the same improvement in relation to speech recognition after 9 months of hearing aid use. Although the two groups were homogeneous vis-à-vis the sociodemographical variables and audiological characteristics, we noticed a mild exit point difference in relation to speech perception in both groups, that is, the Streamline group had a better pre-fitting result without the hearing aid. This may have happened because the randomization process is not perfect for small groups and, moreover, the audiological profile of the patients was not taken into account in this group selection process. What we notice with this result is that the lower the speech recognition at the pre-fitting stage (without the ISAD), more improvement can be obtained during the 9 months, since the scale is shorter. Despite such difference, the speech performance results were similar for both groups at three and nine months after fitting the hearing aid.Besides such findings, in the IOI-HA questionnaire results there were no statistically significant difference in the issues: use, benefit, satisfaction, residual limitation of activities, residual restriction of participation, impact on others and quality of life, and in the total score at three and nine months after fitting the ISAD, which shows that the type of care did not impact the results of this assessment.The high scores in all these aspects assessed, vis-à-vis ISAD fitting  show that the participants from both groups had attitudes favoring their ISADs at three and nine months after fitting. The high mean values found were higher than those in the normative in English - similar results to the ones found in the studies carried out by Williams et al.The statistically significant difference found in the SUS group was striking in the question associated with the benefit, in other words, after nine months using the ISAD there was an improvement vis-à-vis the difficulties in hearing with the hearing aid, and such fact was not found in the Streamline group. On the other hand, the care involving fewer procedures led to similar results as far as speech recognition is concerned for both groups, indicating that it must be better assessed in future studies.This way, we could notice that the two care strategies did not differ from the clinical standpoint in regards of the results obtained from the patients concerning the ISAD fitting. This change in the routine of care, as per the protocol suggested for the auditory health services involving less procedures , did not impact the results obtained in the short and medium run vis-à-vis patient benefits, satisfaction and speech perception.In this study, the anticipated choice of the NAL-NL1 method for the streamline group sped care and helped the audiologist be more focused on the job, providing good ISAD fitting results in this group. We must stress that the hearing health clinic audiologist must be prepared and be knowledgeable concerning the options provided in the ISAD adjustments, because even for validated methods, it is possible that the real gain is below the prescribed gain and the choice of a prescription rule must be based on scientific evidence and must be changed when the clinician finds that the patient's results are not as satisfying as expected.Today, thanks to technological progress, almost all ISAD, of different brands and models, use technology which enables them to adapt to the specific needs of each patientAnother factor is that, today, with the technological progress of ISADs, it is possible to have different adjustments supplied in the same hearing aid device, depending on patient complaint during the tests with the devices. Each different setting programed can be checked by means of the probe microphone measures, which will assess the ISAD performance in an objective fashion, allowing for a better accuracy in the adjustments and on the assessment of the amplification received by the hearing impaired individualMoreover, there are difficulties in obtaining three models of similar ISADs from different brands, so that the tests with patients may be carried out only after the device is indicated. Even three ISAD models from one and the same brand fail in this rigorous demand; thus, professional training and education is fundamental in this field. It is mandatory that the ISAD devices acquired by the SUS should keep a quality, enabling the necessary changes in adjustments and savings should be achieved by employing resources in the updating and motivation of the healthcare professionals to enable them to better fit ISADs, benefiting the population.Another issue that deserves comments is the reduction in the time the health care professional spends with the patient, which is now of 45 minutes per fitting. This maximizes care and increases the number of patients seen. This was not the goal of the present investigation; therefore, its results were not discussed in this paper.Since the clinical results attained were similar for both groups, in this study the Streamline group involved fewer professionals and audiological procedures in their routine care, and with these results we foresee the possibility of caring for a larger number of patients in the auditory healthcare services, and the changes hereby proposed must be considered in changes to Ordinance 587After seven years of the National Policy for Auditory Health Care in our country, we have seen that it is paramount to control and nurture the processes for the population needing such care. The growing demand of patients seeking treatment for their hearing loss in recent years showed the need to think about the speed in seeing this population, having given that another model of care could speed up this process and enable us to see more patients, involving fewer professionals. We know that many auditory healthcare services today have repressed demands and proposals to tackle such problem are being discussed among different groups of professionals associated with scientific societies.In comparison, in other countries there is a broad variety of auditory healthcare services provided and differences concerning the waiting time for a hearing aid. In Sweden, for instance, a person may wait 3 months to receive the device, and this time can be of 18 months in Finland. In some countries there are certain priority groups, for example, workers and children have priority and waiting time is shorter, as it happens in Denmark and NorwayTherefore, optimizing the flow of care will provide greater access of the population to treatment in due time and free up the healthcare teams to bring awareness about hearing preservation and other preventive actions - as proposed by the ordinance.This study enabled us to conclude that the two strategies of care did not differ vis-à-vis the clinical standpoint, nor concerning the results obtained in the assessment of patients for fitting hearing aids. The streamline model , in regards of the assessment of those participating in the study concerning speech perception and important fitting domains - such as the use of an ISAD, benefits, patient satisfaction, participation restriction, activities limitation, hearing impairment impact on others and quality of life, did not impact on the results obtained in the short and medium runs, and all of this must be considered in changes to Ordinance 587