Associations Between Hearing Health and Well-Being in Unilateral Hearing Impairment.

OBJECTIVES: To determine population-based risks of adverse effects on hearing and well-being outcomes associated with unilateral hearing impairment. DESIGN: A group of 40- to 69-year-old adults (n = 861) who reported being able to hear only in one ear and having speech reception thresholds (SRTs) in noise indicating normal hearing in that ear (SRTN/-) was selected from the UK Biobank cohort. The UK Biobank participants with SRTs indicating either normal (SRTN/N, n = 95,514) or symmetrically impaired hearing in both ears (SRTI/I, n = 17,429) were selected as comparison groups. Self-reported difficulty following conversations in noise, tinnitus presence, feeling depressed, lonely, unhappy, and being in poor health or dissatisfied with health were selected as hearing and well-being outcomes. Logistic regression models were used to evaluate the risks of reporting adverse outcomes associated with SRTN/- compared with SRTN/N and SRTI/I while controlling for numerous factors linked to hearing and general health. RESULTS: People with SRTN/- were significantly more likely to report difficulties following conversations in noise (odds ratio, 10.61; 95% confidence interval, 8.83 to 12.75), tinnitus (4.04; 3.51 to 4.66), poor health (1.35; 1.15 to 1.58), health dissatisfaction (1.22; 1.00 to 1.47), and loneliness (1.28; 1.08 to 1.51) compared with people with SRTN/N. Well-being outcomes were similar in the SRTN/- and SRTI/I groups. However, difficulties following conversations in noise (5.35; 4.44 to 6.44) and tinnitus presence (2.66; 2.31 to 3.08) were significantly more likely with SRTN/- than with SRTI/I. The SRTN/- was associated with increased risk of self-reported poor health by 18% (relative risk, 1.18; 95% confidence interval, 1.06 to 1.32) and loneliness by 24% (1.24; 1.07 to 1.43) compared with SRTN/N. The risk of reporting difficulties following conversations in noise increased by 64% (1.64; 1.58 to 1.71) and tinnitus presence by 84% (1.84; 1.69 to 2.01) compared with SRTI/I. The effect of SRTN/- on reporting poor health was similar to that from having other health problems such as hypertension or high cholesterol. CONCLUSIONS: The large increases in the risks of reporting adverse hearing-related outcomes associated with unilateral hearing impairment suggest its specific impact on hearing function in everyday situations. The increased risk of loneliness and poor health indicates that one normally functioning ear is also insufficient to protect against the adverse psychosocial impacts of unilateral hearing impairment. This impact was still significant after controlling for various health-related factors and can lead to perception of poor health comparable to that with having medical problems contributing to life-threatening conditions such as heart disease. The findings suggest the need for effective interventions to address the hearing-related problems and their impact on well-being in people with unilateral hearing impairment.

Hearing aids for mild to moderate hearing loss in adults.

BACKGROUND: The main clinical intervention for mild to moderate hearing loss is the provision of hearing aids. These are routinely offered and fitted to those who seek help for hearing difficulties. By amplifying and improving access to sounds, and speech sounds in particular, the aim of hearing aid use is to reduce the negative consequences of hearing loss and improve participation in everyday life. OBJECTIVES: To evaluate the effects of hearing aids for mild to moderate hearing loss in adults. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; the Cochrane Register of Studies Online; MEDLINE; PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 March 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) of hearing aids compared to a passive or active control in adults with mild to moderate hearing loss. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes in this review were hearing-specific health-related quality of life and the adverse effect pain. Secondary outcomes were health-related quality of life, listening ability and the adverse effect noise-induced hearing loss. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included five RCTs involving 825 participants. The studies were carried out in the USA and Europe, and were published between 1987 and 2017. Risk of bias across the studies varied. Most had low risk for selection, reporting and attrition bias, and a high risk for performance and detection bias because blinding was inadequate or absent.All participants had mild to moderate hearing loss. The average age across all five studies was between 69 and 83 years. The duration of the studies ranged between six weeks and six months.There was a large beneficial effect of hearing aids on hearing-specific health-related quality of life associated with participation in daily life as measured using the Hearing Handicap Inventory for the Elderly (HHIE, scale range 1 to 100) compared to the unaided/placebo condition (mean difference (MD) -26.47, 95% confidence interval (CI) -42.16 to -10.77; 722 participants; three studies) (moderate-quality evidence).There was a small beneficial effect of hearing aids on general health-related quality of life (standardised mean difference (SMD) -0.38, 95% CI -0.55 to -0.21; 568 participants; two studies) (moderate-quality evidence). There was a large beneficial effect of hearing aids on listening ability (SMD -1.88, 95% CI -3.24 to -0.52; 534 participants; two studies) (moderate-quality evidence).Adverse effects were measured in only one study (48 participants) and none were reported (very low-quality evidence). AUTHORS' CONCLUSIONS: The available evidence concurs that hearing aids are effective at improving hearing-specific health-related quality of life, general health-related quality of life and listening ability in adults with mild to moderate hearing loss. The evidence is compatible with the widespread provision of hearing aids as the first-line clinical management in those who seek help for hearing difficulties. Greater consistency is needed in the choice of outcome measures used to assess benefits from hearing aids. Further placebo-controlled studies would increase our confidence in the estimates of these effects and ascertain whether they vary according to age, gender, degree of hearing loss and type of hearing aid.

Tinnitus and Sleep Difficulties After Cochlear Implantation.

OBJECTIVES: To estimate and compare the prevalence of and associations between tinnitus and sleep difficulties in a sample of UK adult cochlear implant users and those identified as potential candidates for cochlear implantation. DESIGN: The study was conducted using the UK Biobank resource, a population-based cohort of 40- to 69-year olds. Self-report data on hearing, tinnitus, sleep difficulties, and demographic variables were collected from cochlear implant users (n = 194) and individuals identified as potential candidates for cochlear implantation (n = 211). These "candidates" were selected based on (i) impaired hearing sensitivity, inferred from self-reported hearing aid use and (ii) impaired hearing function, inferred from an inability to report words accurately at negative signal to noise ratios on an unaided closed-set test of speech perception. Data on tinnitus (presence, persistence, and related distress) and on sleep difficulties were analyzed using logistic regression models controlling for gender, age, deprivation, and neuroticism. RESULTS: The prevalence of tinnitus was similar among implant users (50%) and candidates (52%; p = 0.39). However, implant users were less likely to report that their tinnitus was distressing at its worst (41%) compared with candidates (63%; p = 0.02). The logistic regression model suggested that this difference between the two groups could be explained by the fact that tinnitus was less persistent in implant users (46%) compared with candidates (72%; p < 0.001). Self-reported difficulties with sleep were similar among implant users (75%) and candidates (82%; p = 0.28), but participants with tinnitus were more likely to report sleep difficulties than those without (p < 0.001). The prevalence of sleep difficulties was not related to tinnitus persistence (p = 0.28) or the extent to which tinnitus was distressing (p = 0.55). CONCLUSIONS: The lack of association between tinnitus persistence and sleep difficulties is compatible with the notion that tinnitus is suppressed in implant users primarily during active electrical stimulation and may return when the implant is switched off at night time. This explanation is supported by the similar prevalence of sleep problems among implant users and potential candidates for cochlear implantation, despite differences between the groups in tinnitus persistence and related emotional distress. Cochlear implantation may therefore not be an appropriate intervention where the primary aim is to alleviate sleep difficulties.

Relationship between tinnitus pitch and edge of hearing loss in individuals with a narrow tinnitus bandwidth.

OBJECTIVE: Psychoacoustic measures of tinnitus, in particular dominant tinnitus pitch and its relationship to the shape of the audiogram, are important in determining and verifying pathophysiological mechanisms of the condition. Our previous study postulated that this relationship might vary between different groups of people with tinnitus. For a small subset of participants with narrow tinnitus bandwidth, pitch was associated with the audiometric edge, consistent with the tonotopic reorganization theory. The current study objective was to establish this relationship in an independent sample. DESIGN: This was a retrospective design using data from five studies conducted between 2008 and 2013. STUDY SAMPLE: From a cohort of 380 participants, a subgroup group of 129 with narrow tinnitus bandwidth were selected. RESULTS: Tinnitus pitch generally fell within the area of hearing loss. There was a statistically significant correlation between dominant tinnitus pitch and edge frequency; higher edge frequency being associated with higher dominant tinnitus pitch. However, similar to our previous study, for the majority of participants pitch was more than an octave above the edge frequency. CONCLUSIONS: The findings did not support our prediction and are therefore not consistent with the reorganization theory postulating tinnitus pitch to correspond to the audiometric edge.

Investigating the association between tinnitus severity and symptoms of depression and anxiety, while controlling for neuroticism, in a large middle-aged UK population.

OBJECTIVE: Clinical studies indicate increased risk for depression and anxiety among tinnitus patients. However population data are scarce, and no studies have controlled for neuroticism. We examined associations between tinnitus and symptoms of depression and anxiety in a large UK population, controlling for neuroticism, to explore whether neuroticism, as previously reported, fully explains the association between symptoms of depression and anxiety, and tinnitus. DESIGN: We used the UK Biobank resource. STUDY SAMPLE: 171 728 participants answered hearing questions. RESULTS: Using generalized linear modelling, we examined associations between tinnitus (mild to severe) and symptoms of depression and anxiety. Controlling for neuroticism, patients with severe tinnitus were at increased risk of depression (odds ratio (OR) = 1.27) and anxiety (OR = 1.11) symptoms, compared to those without tinnitus. CONCLUSIONS: Although it is not possible to determine whether tinnitus is a predisposing factor to depression, these results suggest an association. We suggest further exploration to determine the clinical significance of this association. Early psychosocial intervention aimed at reducing anxiety and depression in patients at increased risk might influence the extent to which tinnitus is experienced as troubling, and therefore psychological distress associated with it. Likewise, with tinnitus patients, assessment for anxiety/depression should be considered.

Hearing in middle age: a population snapshot of 40- to 69-year olds in the United Kingdom.

OBJECTIVES: To report population-based prevalence of hearing impairment based on speech recognition in noise testing in a large and inclusive sample of U.K. adults aged 40 to 69 years. The present study is the first to report such data. Prevalence of tinnitus and use of hearing aids is also reported. DESIGN: The research was conducted using the UK Biobank resource. The better-ear unaided speech reception threshold was measured adaptively using the Digit Triplet Test (n = 164,770). Self-report data on tinnitus, hearing aid use, noise exposure, as well as demographic variables were collected. RESULTS: Overall, 10.7% of adults (95% confidence interval [CI] 10.5-10.9%) had significant hearing impairment. Prevalence of tinnitus was 16.9% (95%CI 16.6-17.1%) and hearing aid use was 2.0% (95%CI 1.9-2.1%). Odds of hearing impairment increased with age, with a history of work- and music-related noise exposure, for lower socioeconomic background and for ethnic minority backgrounds. Males were at no higher risk of hearing impairment than females. CONCLUSIONS: Around 1 in 10 adults aged 40 to 69 years have substantial hearing impairment. The reasons for excess risk of hearing impairment particularly for those from low socioeconomic and ethnic minority backgrounds require identification, as this represents a serious health inequality. The underuse of hearing aids has altered little since the 1980s, and is a major cause for concern.

Amplification with hearing aids for patients with tinnitus and co-existing hearing loss.

BACKGROUND: Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. In the current absence of a cure for tinnitus, clinical management typically focuses on reducing the effects of co-morbid symptoms such as distress or hearing loss. Hearing loss is commonly co-morbid with tinnitus and so logic implies that amplification of external sounds by hearing aids will reduce perception of the tinnitus sound and the distress associated with it. OBJECTIVES: To assess the effects of hearing aids specifically in terms of tinnitus benefit in patients with tinnitus and co-existing hearing loss. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 19 August 2013. SELECTION CRITERIA: Randomised controlled trials and non-randomised controlled trials recruiting adults with subjective tinnitus and some degree of hearing loss, where the intervention involves amplification with hearing aids and this is compared to interventions involving other medical devices, other forms of standard or complementary therapy, or combinations of therapies, no intervention or placebo interventions. DATA COLLECTION AND ANALYSIS: Three authors independently screened all selected abstracts. Two authors independently extracted data and assessed those potentially suitable studies for risk of bias. For studies meeting the inclusion criteria, we used the mean difference (MD) to compare hearing aids with other interventions and controls. MAIN RESULTS: One randomised controlled trial (91 participants) was included in this review. We judged the trial to have a low risk of bias for method of randomisation and outcome reporting, and an unclear risk of bias for other criteria. No non-randomised controlled trials meeting our inclusion criteria were identified. The included study measured change in tinnitus severity (primary measure of interest) using a tinnitus questionnaire measure, and change in tinnitus loudness (secondary measure of interest) on a visual analogue scale. Other secondary outcome measures of interest, namely change in the psychoacoustic characteristics of tinnitus, change in self reported anxiety, depression and quality of life, and change in neurophysiological measures, were not investigated in this study. The included study compared hearing aid use to sound generator use. The estimated effect on change in tinnitus loudness or severity as measured by the Tinnitus Handicap Inventory score was compatible with benefits for both hearing aids or sound generators but no difference was found between the two alternative treatments (MD -0.90, 95% confidence interval (CI) -7.92 to 6.12) (100-point scale); moderate quality evidence. No negative or adverse events were reported. AUTHORS' CONCLUSIONS: The current evidence base for hearing aid prescription for tinnitus is limited. To be useful, future studies should make appropriate use of blinding and be consistent in their use of outcome measures. Whilst hearing aids are sometimes prescribed as part of tinnitus management, there is currently no evidence to support or refute their use as a more routine intervention for tinnitus.

Vision impairment and dual sensory problems in middle age.

PURPOSE: Vision and hearing impairments are known to increase in middle age. In this study we describe the prevalence of vision impairment and dual sensory impairment in UK adults aged 40-69 years in a very large and recently ascertained data set. The associations between vision impairment, age, sex, socioeconomic status, and ethnicity are reported. METHODS: This research was conducted using the UK Biobank Resource, with subsets of UK Biobank data analysed with respect to self-report of eye problems and glasses use. Better-eye visual acuity with habitually worn refractive correction was assessed with a logMAR chart (n = 116,682). Better-ear speech reception threshold was measured with an adaptive speech in noise test, the Digit Triplet Test (n = 164,770). Prevalence estimates were weighted with respect to UK 2001 Census data. RESULTS: Prevalence of mild visual impairment (VA >0.1 logMAR (6/7.5, 20/25) and ≥0.48 (6/18, 20/60)) and low vision (VA >0.48 (6/18, 20/60) and ≥1.3 (6/120, 20/400)) was estimated at 13.1% (95% CI 12.9-13.4) and 0.8% (95% CI 0.7-0.9), respectively. Use of glasses was 88.0% (95% CI 87.9-88.1). The prevalence of dual sensory impairment was 3.1% (95% CI 3.0-3.2) and there was a nine-fold increase in the prevalence of dual sensory problems between the youngest and oldest age groups. Older adults, those from low socioeconomic and ethnic minority backgrounds were most at risk for vision problems. CONCLUSIONS: Mild vision impairment is common in middle aged UK adults, despite widespread use of spectacles. Increased likelihood of vision impairment with older age and with ethnic minorities is of concern given ageing and more ethnically diverse populations. Possible barriers to optometric care for those from low socioeconomic and ethnic minority backgrounds may require attention. A higher than expected prevalence of dual impairment suggests that hearing and vision problems share common causes. Optometrists should consider screening for hearing problems, particularly among older adults.

Comparison of the benefits of cochlear implantation versus contra-lateral routing of signal hearing aids in adult patients with single-sided deafness: study protocol for a prospective within-subject longitudinal trial.

BACKGROUND: Individuals with a unilateral severe-to-profound hearing loss, or single-sided deafness, report difficulty with listening in many everyday situations despite having access to well-preserved acoustic hearing in one ear. The standard of care for single-sided deafness available on the UK National Health Service is a contra-lateral routing of signals hearing aid which transfers sounds from the impaired ear to the non-impaired ear. This hearing aid has been found to improve speech understanding in noise when the signal-to-noise ratio is more favourable at the impaired ear than the non-impaired ear. However, the indiscriminate routing of signals to a single ear can have detrimental effects when interfering sounds are located on the side of the impaired ear. Recent published evidence has suggested that cochlear implantation in individuals with a single-sided deafness can restore access to the binaural cues which underpin the ability to localise sounds and segregate speech from other interfering sounds. METHODS/DESIGN: The current trial was designed to assess the efficacy of cochlear implantation compared to a contra-lateral routing of signals hearing aid in restoring binaural hearing in adults with acquired single-sided deafness. Patients are assessed at baseline and after receiving a contra-lateral routing of signals hearing aid. A cochlear implant is then provided to those patients who do not receive sufficient benefit from the hearing aid. This within-subject longitudinal design reflects the expected care pathway should cochlear implantation be provided for single-sided deafness on the UK National Health Service. The primary endpoints are measures of binaural hearing at baseline, after provision of a contra-lateral routing of signals hearing aid, and after cochlear implantation. Binaural hearing is assessed in terms of the accuracy with which sounds are localised and speech is perceived in background noise. The trial is also designed to measure the impact of the interventions on hearing- and health-related quality of life. DISCUSSION: This multi-centre trial was designed to provide evidence for the efficacy of cochlear implantation compared to the contra-lateral routing of signals. A purpose-built sound presentation system and established measurement techniques will provide reliable and precise measures of binaural hearing. TRIAL REGISTRATION: Current Controlled Trials http://www.controlled-trials.com/ISRCTN33301739 (05/JUL/2013).

MPES-R: Multi-Parameter Evidence Synthesis in R for Survival Extrapolation-A Tutorial.

Survival extrapolation often plays an important role in health technology assessment (HTA), and there are a range of different approaches available. Approaches that can leverage external evidence (i.e. data or information collected outside the main data source of interest) may be helpful, given the extent of uncertainty often present when determining a suitable survival extrapolation. One of these methods is the multi-parameter evidence synthesis (MPES) approach, first proposed for use in HTA by Guyot et al., and more recently by Jackson. While MPES has potential benefits over conventional extrapolation approaches (such as simple or flexible parametric models), it is more computationally complex and requires use of specialist software. This tutorial presents an introduction to MPES for HTA, alongside a user-friendly, publicly available operationalisation of Guyot's original MPES that can be executed using the statistical software package R. Through two case studies, both Guyot's and Jackson's MPES approaches are explored, along with sensitivity analyses relevant to HTA. Finally, the discussion section of the tutorial details important considerations for analysts considering use of an MPES approach, along with potential further developments. MPES has not been used often in HTA, and so there are limited examples of how it has been used and perceived. However, this tutorial may aid future research efforts exploring the use of MPES further.

"Don't keep me waiting": estimating the impact of reduced vein-to-vein time on lifetime US 3L+ LBCL patient outcomes.

ABSTRACT: Chimeric antigen receptor T-cell therapy (CAR T) has revolutionized the treatment of hematological cancers. Its production requires a complex logistical process, and the time from leukapheresis to patient infusion (known as the vein-to-vein time [V2VT]) can be long during which a patients clinical condition may deteriorate. This study was designed to estimate the benefits of reduced V2VT for third-line or later (3L+) relapsed/refractory large B-cell lymphoma (R/R LBCL) patients treated with CAR T. A mathematical model was developed to estimate the lifetime outcomes of a hypothetical cohort of patients who had either a long or short V2VT. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were estimated. Scenario analyses were performed to assess the robustness of results to key assumptions. The results of the model show that reducing V2VT from 54 days (tisa-cel median V2VT; JULIET) to 24 days (axi-cel median V2VT; ZUMA-1) led to a 3.2-year gain in life expectancy (4.2 vs 7.7 LYs), and 2.4 additional QALYs (3.2 vs 5.6) per patient. Furthermore, a shorter V2VT was shown to be cost-effective under conventional willingness-to-pay thresholds in the United States. Results are driven by a higher infusion rate and a better efficacy of CAR T for those infused. Scenario analyses using a smaller difference in V2VT (24 vs 36 days) produced consistent results. Our study is the first to quantify lifetime V2VT-related outcomes for 3L+ R/R LBCL patients treated with CAR T utilizing currently available evidence. Shorter V2VTs led to improved outcomes, demonstrating the importance of timely infusion achievable by faster manufacturing times and optimization of hospital delivery.

Treatment-Switching Adjustment of Overall Survival in CheckMate 227 Part 1 Evaluating First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy for Metastatic Nonsmall Cell Lung Cancer.

OBJECTIVES: CheckMate 227 (NCT02477826) evaluated first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic nonsmall cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression ≥ 1% or < 1% and no EGFR/ALK alterations. However, many patients randomized to chemotherapy received subsequent immunotherapy. Here, overall survival (OS) and relative OS benefit of nivolumab-plus-ipilimumab were adjusted for potential bias introduced by treatment switching. MATERIALS AND METHODS: Treatment-switching adjustment analyses were conducted following the NICE Decision Support Unit Technical Support Document 16, for CheckMate 227 Part 1 OS data from treated patients (database lock, July 2, 2019). Inverse probability of censoring weighting (IPCW) was used in the base-case analysis; other methods were explored as sensitivity analyses. RESULTS: Of 1166 randomized patients, 391 (PD-L1 ≥ 1%) and 185 (PD-L1 < 1%) patients received nivolumab-plus-ipilimumab; 387 (PD-L1 ≥ 1%) and 183 (PD-L1 < 1%) patients received chemotherapy, with 29.3-month minimum follow-up. Among chemotherapy-treated patients, 169/387 (43.7%; PD-L1 ≥ 1%) and 66/183 (36.1%; PD-L1 < 1%) switched to immunotherapy poststudy. Among treated patients, median OS was 17.4 months with nivolumab-plus-ipilimumab versus 14.9 months with chemotherapy (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68-0.95) in the PD-L1 ≥ 1% subgroup and 17.1 versus 12.4 months (HR, 0.62; 95% CI, 0.49-0.80) in the PD-L1 < 1% subgroup. After treatment-switching adjustment using IPCW, the HR (95% CI) for OS for nivolumab-plus-ipilimumab versus chemotherapy was reduced to 0.68 (0.56-0.83; PD-L1 ≥ 1%) and 0.53 (0.40-0.69; PD-L1 < 1%). Sensitivity analyses supported the robustness of the results. CONCLUSION: Treatment-switching adjustments resulted in a greater estimated relative OS benefit with first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic NSCLC.

Impact of pneumococcal conjugate vaccines on healthcare utilization and direct costs for otitis media in children ≤2 years of age in two Swedish regions.

In Sweden, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 and replaced by the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) or the 13- valent PCV (PCV13) from late 2009. We assessed the impact of PCVs on rates of antibiotic prescribing, tympanostomy tube placement (TTP), and healthcare resource utilization and direct costs of physician- diagnosed otitis media/acute otitis media (OM) in children ≤2 years of age living in Skåne (PCV7 then PHiD- CV) or Västra Götalandsregionen (VGR; PCV7 then PCV13). Retrospective cohort study using linked patient- level data from national and regional (Skåne and VGR) healthcare databases in Sweden from July 1, 2005, to December 31, 2013 (NCT02742753). Descriptive time-series analyses showed antibiotic prescriptions and TTP incidence declined after PHiD-CV/PCV13 introduction versus the pre-PCV period. The annualized mean frequencies of antibiotic use, primary care visits, outpatient visits, TTP and myringotomy procedures all decreased after PHiD-CV/PCV13 compared with pre-PCV cohorts. Annualized mean total OM-associated healthcare costs decreased in the PCV7 versus pre-PCV cohorts by 20.0% in Skåne and 10.2% in VGR, and further declined in the PHiD-CV and PCV13 cohorts (20.7% and 15.3%, respectively, relative to the PCV7 cohort), although the duration of PCV7 use differed between regions. Decreases in adjusted annualized cost ratios between cohorts per child susceptible to OM were statistically significant after PCV7 introduction and again with either PHiD-CV or PCV13 introduction in both regions. Following sequential PCV introduction, OM-related healthcare utilization and associated costs decreased in the study regions in Sweden. PLAIN LANGUAGE SUMMARY: What is the context?Otitis media is one of the most frequent reasons for healthcare visits and antibiotic use among young children. Although it is considered as a mild illness, the overall economic burden is substantial due to its high frequency.Otitis media can be caused by different bacteria including Streptococcus pneumoniae, which is also responsible for pneumonia and meningitis. Pneumococcal conjugate vaccines Prevenar (Pfizer Inc.), Synflorix (GSK), and Prevenar 13 (Pfizer Inc.) protect against pneumococcal diseases and reduce its occurrence.However, it is not known how the routine use of these vaccines may affect otitis media-related healthcare resources and costs.What is new?In this study, we assessed trends in rates of healthcare utilization and associated costs due to otitis media in young children before (2005-2008) and after (2009-2013) use of pneumococcal conjugate vaccines. The study was conducted in two Swedish regions; one used Prevenar then Synflorix, while the other used Prevenar then Prevenar 13.We found that compared to the period before pneumococcal conjugate vaccine implementation, the postpneumococcal conjugate vaccine period was associated with:What is the impact on current thinking?The use of pneumococcal conjugate vaccines effectively reduces healthcare utilization and resources associated with otitis mediaThis indirect effect on the reduction of otitis media burden provides further benefit to the implementation of pneumococcal vaccination.

Re-examining the relationship between audiometric profile and tinnitus pitch.

OBJECTIVE: We explored the relationship between audiogram shape and tinnitus pitch to answer questions arising from neurophysiological models of tinnitus: 'Is the dominant tinnitus pitch associated with the edge of hearing loss?' and 'Is such a relationship more robust in people with narrow tinnitus bandwidth or steep sloping hearing loss?' DESIGN: A broken-stick fitting objectively quantified slope, degree and edge of hearing loss up to 16 kHz. Tinnitus pitch was characterized up to 12 kHz. We used correlation and multiple regression analyses for examining relationships with many potentially predictive audiometric variables. STUDY SAMPLE: 67 people with chronic bilateral tinnitus (43 men and 24 women, aged from 22 to 81 years). RESULTS: In this ample of 67 subjects correlation failed to reveal any relationship between the tinnitus pitch and the edge frequency. The tinnitus pitch generally fell within the area of hearing loss. The pitch of the tinnitus in a subset of subjects with a narrow tinnitus bandwidth (n = 23) was associated with the audiometric edge. CONCLUSIONS: Our findings concerning subjects with narrow tinnitus bandwidth suggest that this can be used as an a priori inclusion criterion. A large group of such subjects should be tested to confirm these results.

The effect of pneumococcal conjugate vaccines on otitis media from 2005 to 2013 in children aged ≤5 years: a retrospective cohort study in two Swedish regions.

Seven-valent pneumococcal conjugate vaccine (PCV7) was introduced to Sweden in 2009 and replaced by pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) or 13-valent PCV (PCV13) from late 2009. A retrospective cohort study assessed the impact of PCVs on otitis media/acute otitis media (OM) in children aged ≤5 years (NCT02742753) living in Skåne (PCV7 then PHiD-CV) or Västra Götalandsregionen (PCV7 then PCV13) between 2005 and 2013 using linked regional and national databases. Time-series analyses described differences between pre-PCV and post-PCV eras. Adjusted age-period-cohort (APC) predictive models estimated vaccine effectiveness and OM incidence ratios between PCV cohorts. Time-to-first OM diagnosis was estimated in ≤2 year-olds by survival analysis using a Cox proportional hazards model. Descriptive interrupted time-series analyses showed OM incidence in ≤2 year-olds declined by 42% (Skåne) and 25% (Västra Götalandsregionen) after PHiD-CV/PCV13, respectively, versus pre-PCV, but baseline OM incidence and duration of PCV7 use differed between regions. In adjusted APC models, OM incidence decreased after PHiD-CV by 9.9% (95% confidence interval [CI]: 4.4; 15.1, p < .001) and PCV13 by 2.3% (95%CI: -3.2; 7.6, p = .401) compared with pre-PCV. Both PHiD-CV and PCV13 decreased the risk of first OM diagnosis: hazard ratio (95%CI) for PHiD-CV relative to pre-PCV 0.67 (0.65; 0.69); 0.87 (0.85; 0.89) for PCV13 relative to pre-PCV; p < .001 for both comparisons. Within the limitations of this study conducted in two large Swedish regions, descriptive time-series analyses showed that OM incidence rates declined following the introduction of PHiD-CV and PCV13; however, this reduction only reached statistical significance for PHiD-CV in the adjusted APC models.

Risk Prediction Using Bayesian Networks: An Immunotherapy Case Study in Patients With Metastatic Renal Cell Carcinoma.

PURPOSE: To address the need for more accurate risk stratification models for cancer immuno-oncology, this study aimed to develop a machine-learned Bayesian network model (BNM) for predicting outcomes in patients with metastatic renal cell carcinoma (mRCC) being treated with immunotherapy. METHODS: Patient-level data from the randomized, phase III CheckMate 025 clinical trial comparing nivolumab with everolimus for second-line treatment in patients with mRCC were used to develop the BNM. Outcomes of interest were overall survival (OS), all-cause adverse events, and treatment-related adverse events (TRAE) over 36 months after treatment initiation. External validation of the model's predictions for OS was conducted using data from select centers from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). RESULTS: Areas under the receiver operating characteristic curve (AUCs) for BNM-based classification of OS using baseline data were 0.74, 0.71, and 0.68 over months 12, 24, and 36, respectively. AUC for OS at 12 months increased to 0.86 when treatment response and progression status in year 1 were included as predictors; progression and response at 12 months were highly prognostic of all outcomes over the 36-month period. AUCs for adverse events and treatment-related adverse events were approximately 0.6 at 12 months but increased to approximately 0.7 by 36 months. Sensitivity analysis comparing the BNM with machine learning classifiers showed comparable performance. Test AUC on IMDC data for 12-month OS was 0.71 despite several variable imbalances. Notably, the BNM outperformed the IMDC risk score alone. CONCLUSION: The validated BNM performed well at prediction using baseline data, particularly with the inclusion of response and progression at 12 months. Additionally, the results suggest that 12 months of follow-up data alone may be sufficient to inform long-term survival projections in patients with mRCC.

The Development of a New Questionnaire to Measure the Burden of Immunoglobulin Treatment in Patients with Primary Immunodeficiencies: The IgBoT-35.

PURPOSE: To describe the development and psychometric testing of a new questionnaire to measure the burden of immunoglobulin treatment (Ig) from the perspective of patients with primary immunodeficiencies (PID). PATIENTS AND METHODS: An online, cross-sectional survey was administered to PID patients across 10 countries (nine European and Canada) who were receiving either intravenous (IVIg) or subcutaneous (SCIg) immunoglobulin therapy. The range and distribution of the responses (ie, levels of missing data, floor and ceiling effects), exploratory factor analysis (using factor loadings of 0.4 or greater) and measures of internal consistency reliability (ie, Cronbach's alpha coefficient, inter-item and item-total correlations) were used to identify the domain and item pool. RESULTS: In total, 472 patients completed the questionnaire, of which 395 were included in the analysis (32% underwent IVIg and 67% underwent SCIg). The final instrument contained 34 items across eight domains of treatment burden (time, organisation and planning, leisure and social, interpersonal relationships, employment and education, travel, consequences of treatment and emotional) and an additional Ig treatment burden global question at the end of the measure. All the scales achieved good internal reliability (Cronbach's alpha coefficient ranged from 0.70 to 0.85) and, with the exception of one item exceeded the minimum threshold of 0.35 for item-total correlations. Treatment burden was lower than anticipated across the different treatment routes and countries, although overall was more burdensome for patients undergoing IVIg compared to SCIg treatment. CONCLUSION: The IgBoT-35 appears to be a reliable, patient-generated questionnaire and may help to identify more individualised and preferred therapies for the PID patient when used in clinical practice. A new survey with a sample of US patients is currently being undertaken to further establish its validity and conceptual model. The overall Ig burden of treatment scores appeared to be low. PID patient preferences are important to guide treatment decisions and ensuring patients receive the right treatment at the right time.

A systematic review of the reporting of tinnitus prevalence and severity.

INTRODUCTION: There is no standard diagnostic criterion for tinnitus, although some clinical assessment instruments do exist for identifying patient complaints. Within epidemiological studies the presence of tinnitus is determined primarily by self-report, typically in response to a single question. Using these methods prevalence figures vary widely. Given the variety of published estimates worldwide, we assessed and collated published prevalence estimates of tinnitus and tinnitus severity, creating a narrative synthesis of the data. The variability between prevalence estimates was investigated in order to determine any barriers to data synthesis and to identify reasons for heterogeneity. METHODS: and analysis: A systematic review included all adult population studies reporting the prevalence of tinnitus from January 1980 to July 2015. We searched five databases (Embase, Medline, PsychInfo, CINAHL and Web Of Science), using a combination of medical subject headings (MeSH) and relevant text words. Observational studies including cross-sectional studies were included, but studies estimating the incidence of tinnitus (e.g. cohort studies) were outside the scope of this systematic review. RESULTS: The databases identified 875 papers and a further 16 were identified through manual searching. After duplicates were removed, 515 remained. On the basis of the title, abstract and full-text screening, 400, 48 and 27 papers respectively were removed. This left 40 papers, reporting 39 different studies, for data extraction. Sixteen countries were represented, with the majority of the studies from the European region (38.5%). Publications since 2010 represented half of all included studies (48.7%). Overall prevalence figures for each study ranged from 5.1% to 42.7%. For the 12 studies that used the same definition of tinnitus, prevalence ranged from 11.9% to 30.3%. Twenty-six studies (66.7%) reported tinnitus prevalence by different age groups, and generally showed an increase in prevalence as age increases. Half the studies reported tinnitus prevalence by gender. The pattern generally showed higher tinnitus prevalence among males than females. There were 8 different types of definitions of tinnitus, the most common being "tinnitus lasting for more than five minutes at a time" (34.3%). Only seven studies gave any justification for the question that was used, or acknowledged the lack of standard questions for tinnitus. There is widespread inconsistency in defining and reporting tinnitus, leading to variability in prevalence estimates among studies. Nearly half of the included studies had a high risk of bias and this limits the generalisability of prevalence estimates. In addition, the available prevalence data is heterogeneous thereby preventing the ability to pool the data and perform meta-analyses. Sources of heterogeneity include different diagnostic criteria, different age groups, different study focus and differences in reporting and analysis of the results. Heterogeneity thus made comparison across studies impracticable. CONCLUSION: Deriving global estimates of the prevalence of tinnitus involves combining results from studies which are consistent in their definition and measurement of tinnitus, survey methodology and in the reporting and analysis of the results. Ultimately comparison among studies is unachievable without such consistency. The strength of this systematic review is in providing a record of all the available, recent epidemiological data in each global region and in making recommendations for promoting standardisation.