Benefit-Harm Analysis for Informed Decision Making on Participating in Colorectal Cancer Screening: A Modeling Study.

OBJECTIVES: To facilitate informed decision making on participating in colorectal cancer (CRC) screening, we assessed the benefit-harm balance of CRC screening for a wide range of subgroups over different time horizons. METHODS: The study combined incidence proportions of benefits and harms of (not) participating in CRC screening estimated by the Adenoma and Serrated pathway to CAncer microsimulation model, a preference eliciting survey, and benefit-harm balance modeling combining all outcomes to determine the net health benefit of CRC screening over 10, 20, and 30 years. Probability of net health benefit was estimated for 210 different subgroups based on age, sex, previous participation in CRC screening, and lifestyle. RESULTS: CRC screening was net beneficial in 183 of 210 subgroups over 30 years (median probability [MP] of 0.79, interquartile range [IQR] of 0.69-0.85) across subgroups. Net health benefit was greater for men (MP 0.82; IQR 0.69-0.89) than women (MP 0.76; IQR 0.67-0.83) and for those without history of participation in previous screenings (MP 0.84; IQR 0.80-0.89) compared with those with (MP 0.69; IQR 0.59-0.75). Net health benefit decreased with increasing age, from MP of 0.84 (IQR 0.80-0.86) at age 55 to 0.61 (IQR 0.56-0.71) at age 75. Shorter time horizons led to lower benefit, with MP of 0.70 (IQR 0.62-0.80) over 20 years and 0.54 (IQR 0.48-0.67) over 10 years. CONCLUSIONS: Our benefit-harm analysis provides information about net health benefit of screening participation, based on important characteristics and preferences of individuals, which could assist screening invitees in making informed decisions on screening participation.

The Lifelines Cohort Study: Prevalence of Tinnitus Associated Suffering and Behavioral Outcomes in Children and Adolescents.

OBJECTIVES: Tinnitus in children and adolescents is relatively unexplored territory. The available literature is limited and the reported prevalence of tinnitus suffering varies widely due to the absence of a definition for pediatric tinnitus. The impact on daily life seems to be lower than in the adult population. It is unclear if children who suffer from tinnitus, like adults, also experience psychological distress like anxiety or depressive symptoms. A better understanding of tinnitus in children and its impact on daily life could provide more insight into the actual size of the problem and could give direction for future studies to investigate the cause of progression of tinnitus. DESIGN: A cross-sectional study was performed using the Dutch Lifelines population-based cohort of people living in the north of the Netherlands. A total of 4964 children (4 to 12 years of age) and 2506 adolescents (13 to 17 years of age) were included. The presence of tinnitus suffering and behavioral outcomes were assessed with a single-item question and the Child Behavioral Checklist or the Youth Self Report questionnaire respectively. The associations of behavioral outcomes and tinnitus suffering were analyzed using univariate binary regressions. RESULTS: The prevalence of tinnitus suffering in children was 3.3 and 12.8% in adolescents. Additionally, 0.3% of the children and 1.9% of the adolescents suffered a lot or extremely of their tinnitus. Externalizing and internalizing problems were associated with tinnitus in adolescents. Internalizing problems were associated with tinnitus in children. CONCLUSIONS: The prevalence of tinnitus suffering in this sample of the general population is comparable to other population-based studies. A low percentage of children (0.3%) or adolescents (1.9%) suffered a lot or extremely of their tinnitus. Tinnitus suffering is associated with all behavioral outcome subscales in adolescents and with internalizing problems in children, although the effect sizes were very small. Future research should focus on achieving a consensus for the definition of pediatric tinnitus and on the development of a validated outcome measure.

One-year psychophysical evaluation of COVID-19-induced olfactory disorders: a prospective cohort study.

BACKGROUND: Olfactory disorders are common in COVID-19. While many patients recover within weeks, a notable number of patients suffer from prolonged olfactory disorders. Much research has focused on the acute phase of olfactory disorders in COVID-19; however, there is still inconsistency regarding the prognosis. We aim to assess both objective and subjective olfactory function in patients with persisting olfactory disorders following COVID-19, 1 year after diagnosis. METHODS: We objectively measured olfactory function in 77 patients who initially had COVID-19-induced smell disorders, 1 year after confirmed diagnosis. These patients previously underwent two objective measurements at approximately 3 and 6 months after COVID-19, in the context of the COCOS trial (COrticosteroids for COvid-19-induced loss of Smell). The main outcome measurement was TDI score (threshold-discrimination-identification) on Sniffin' Sticks Test (SST). Secondary outcomes included objective gustatory function on Taste Strip Test (TST), self-reported olfactory, gustatory and trigeminal function on a visual analogue scale (VAS) and outcomes on questionnaires about quality of life, and nasal symptoms. RESULTS: The findings of this study show that 1 year following COVID-19, the median TDI score increased to 30.75 (IQR 27.38-33.5), regarded as normosmia. The median TDI score started at 21.25 (IQR 18.25-24.75) at baseline and increased to 27.5 (IQR 23.63-30.0) at 6 months following COVID-19. The increase of 9.5 points on the TDI score between baseline and 1 year after COVID-19 marks a clinically relevant improvement. Regarding the self-reported VAS score (1-10) on sense of smell, it increased from 1.2 (IQR 0.4-3.0) at baseline to 3.2 (IQR 1.4-6.0) at 6 months and further improved up to 6.1 (IQR 2.7-7.5) after 1 year. Objective gustatory function increased with 2 points on TST a year after diagnosis. Self-reported olfactory, gustatory, and trigeminal functions also improved over time, as did quality of life. CONCLUSIONS: Objective and self-reported olfactory function continued to improve 1 year after COVID-19. The median TDI score of 30.75 (IQR 27.38-33.5) is regarded as normosmia, which is a favorable outcome. However, the rate of improvement on TDI score reduces over time.

Perceived Importance of the Benefits and Harms of Colorectal Cancer Screening: A Best-Worst Scaling Study.

OBJECTIVES: To elicit the relative importance of the benefits and harms of colorectal cancer (CRC) screening among potential screening participants in the Dutch population. METHODS: In a consensus meeting with 11 experts, risk reduction of CRC and CRC deaths (benefits) and complications from colonoscopy, stress of receiving positive fecal immunological test (FIT) results, as well as false-positive and false-negative FIT results (harms) were selected as determinant end points to consider during decision making. We conducted an online best-worst scaling survey among adults aged 55 to 75 years from the Dutch Health Care Consumer Panel of The Netherlands Institute for Health Services Research to elicit preference values for these outcomes. The preference values were estimated using conditional logit regression. RESULTS: Of 265 participants, 234 (89%) had ever participated in CRC screening. Compared with the stress of receiving a positive FIT result, the outcome perceived most important was the risk of CRC death (odds ratio [OR] 4.5; 95% confidence interval [CI] 3.9-5.1), followed by risk of CRC (OR 4.1; 95% CI 3.6-4.7), a false-negative FIT result (OR 3.1; 95% CI 2.7-3.5), colonoscopy complications (OR 1.6; 95% CI 1.4-1.8), and a false-positive FIT result (OR 1.4; 95% CI 1.3-1.6). The magnitude of these differences in perceived importance varied according to age, educational level, ethnic background, and whether the individual had previously participated in CRC screening. CONCLUSION: Dutch men and women eligible for FIT-based CRC screening perceive the benefits of screening to be more important than the harms.

Prednisolone does not improve olfactory function after COVID-19: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Prednisolone has been suggested as a treatment for olfactory disorders after COVID-19, but evidence is scarce. Hence, we aimed to determine the efficacy of a short oral prednisolone treatment on patients with persistent olfactory disorders after COVID-19. METHODS: We performed a randomized, double-blind, placebo-controlled, single-centered trial in the Netherlands. Patients were included if they were > 18 years old and if they had persistent (> 4 weeks) olfactory disorders within 12 weeks after a confirmed COVID-19 test. The treatment group received oral prednisolone 40 mg once daily for 10 days and the placebo group received matching placebo. In addition, all patients performed olfactory training. The primary outcome was the objective olfactory function on Sniffin' Sticks Test (SST) 12 weeks after the start of treatment, measured in Threshold-Discrimination-Identification (TDI) score. Secondary outcomes were objective gustatory function assessed by the Taste Strip Test (TST) and subjective self-reported outcomes on questionnaires about olfactory, gustatory and trigeminal function, quality of life, and nasal symptoms. The CONSORT 2010 guideline was performed. RESULTS: Between November 2021 and February 2022, we included 115 eligible patients, randomly assigned to the treatment (n = 58) or placebo group (n = 57). No difference in olfactory function between groups was obtained after 12 weeks. Median TDI score on SST was 26.8 (IQR 23.6-29.3) in the placebo group and 28.8 (IQR 24.0-30.9) in the prednisolone group, with a median difference of 2.0 (95% CI 0.75 to 1.5). There was similar improvement on olfactory function in both groups after 12 weeks. Furthermore, on secondary outcomes, we obtained no differences between groups. CONCLUSIONS: This trial shows that prednisolone does not improve olfactory function after COVID-19. Therefore, we recommend not prescribing prednisolone for patients with persistent olfactory disorders after COVID-19. TRIAL REGISTRATION: This trial is registered on the ISRCTN registry with trial ID ISRCTN70794078.

Ophthalmological Evaluation in Children Presenting With a Primary Brain Tumor.

BACKGROUND: Children with a brain tumor are prone to develop visual impairment, which to date is often underestimated and unrecognized. Our aim was to assess the prevalence of ophthalmological evaluation and abnormal ophthalmological findings, and investigate whether demographic and tumor-related characteristics are associated with abnormal ophthalmological findings in children presenting with a primary brain tumor. METHODS: Medical records of all 90 children diagnosed with a primary brain tumor between June 2018 and May 2019 and treated at the Princess Máxima Center for Pediatric Oncology, a tertiary referral center in the Netherlands, were retrospectively reviewed. Univariate regression analysis was used to investigate associations between demographic, tumor-related and clinical characteristics, and abnormal ophthalmological findings. RESULTS: Sixty children (34 male [56.7%]; median [range] age, 9.3 [0-16.9] years) underwent ophthalmological evaluation within 6 weeks before or after diagnosis, 11 children (5 male [45.5%]; median [range] age, 5.7 [0.1-17.2] years) were seen more than 6 weeks before or after diagnosis, and 19 children (7 male [36.8%]; median [range] age, 7.2 [1.9-16.6] years) did not receive ophthalmological evaluation within at least 6 months from diagnosis. A total of 19 children (21.1%) presented with visual symptoms as first sign leading to the diagnosis of a brain tumor. Children who presented with visual symptoms (odds ratio [OR], 22.52; 95% confidence interval [CI], 4.90-103.60) and/or hydrocephalus (OR, 3.60; 95% CI, 1.38-9.36) at diagnosis were more often seen for ophthalmological evaluation. The most common abnormal ophthalmological findings were eye movement disorders (66.0%), papilledema (44.1%), and visual field defects (58.1%). Eye movement disorders occurred more frequently in patients with an infratentorial tumor (OR, 4.71; 95% CI, 1.03-21.65). The risk of papilledema was associated with older age (OR, 1.19; 95% CI, 1.05-1.34), hydrocephalus (OR, 9.63; 95% CI, 2.68-34.61), and infratentorial (OR, 9.11; 95% CI, 1.77-46.78) and supratentorial (OR, 13.13; 95% CI, 1.92-89.52) tumors. CONCLUSIONS: In this study, most children with a primary brain tumor underwent ophthalmological evaluation around diagnosis, 21% of the children were not evaluated. The high prevalence of abnormal ophthalmological findings stresses the importance of early standardized ophthalmological evaluation to detect visual impairment and provide timely treatment to potentially prevent permanent visual loss.

Linguistic Complexity of Speech Recognition Test Sentences and Its Influence on Children's Verbal Repetition Accuracy.

OBJECTIVES: Speech recognition (SR)-tests have been developed for children without considering the linguistic complexity of the sentences used. However, linguistic complexity is hypothesized to influence correct sentence repetition. The aim of this study is to identify lexical and grammatical parameters influencing verbal repetition accuracy of sentences derived from a Dutch SR-test when performed by 6-year-old typically developing children. DESIGN: For this observational, cross-sectional study, 40 typically developing children aged 6 were recruited at four primary schools in the Netherlands. All children performed a sentence repetition task derived from an SR-test for adults. The sentence complexity was described beforehand with one lexical parameter, age of acquisition, and four grammatical parameters, specifically sentence length, prepositions, sentence structure, and verb inflection. A multiple logistic regression analysis was performed. RESULTS: Sentences with a higher age of acquisition (odds ratio [OR] = 1.59) or greater sentence length (OR = 1.28) had a higher risk of repetition inaccuracy. Sentences including a spatial (OR = 1.25) or other preposition (OR = 1.25) were at increased risk for incorrect repetition, as were complex sentences (OR = 1.69) and sentences in the present perfect (OR = 1.44) or future tense (OR = 2.32). CONCLUSIONS: The variation in verbal repetition accuracy in 6-year-old children is significantly influenced by both lexical and grammatical parameters. Linguistic complexity is an important factor to take into account when assessing speech intelligibility in children.

Routine laboratory testing to determine if a patient has COVID-19.

BACKGROUND: Specific diagnostic tests to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resulting COVID-19 disease are not always available and take time to obtain results. Routine laboratory markers such as white blood cell count, measures of anticoagulation, C-reactive protein (CRP) and procalcitonin, are used to assess the clinical status of a patient. These laboratory tests may be useful for the triage of people with potential COVID-19 to prioritize them for different levels of treatment, especially in situations where time and resources are limited. OBJECTIVES: To assess the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID-19. SEARCH METHODS: On 4 May 2020 we undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: We included both case-control designs and consecutive series of patients that assessed the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID-19. The reference standard could be reverse transcriptase polymerase chain reaction (RT-PCR) alone; RT-PCR plus clinical expertise or and imaging; repeated RT-PCR several days apart or from different samples; WHO and other case definitions; and any other reference standard used by the study authors. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each included study. They also assessed the methodological quality of the studies, using QUADAS-2. We used the 'NLMIXED' procedure in SAS 9.4 for the hierarchical summary receiver operating characteristic (HSROC) meta-analyses of tests for which we included four or more studies. To facilitate interpretation of results, for each meta-analysis we estimated summary sensitivity at the points on the SROC curve that corresponded to the median and interquartile range boundaries of specificities in the included studies. MAIN RESULTS: We included 21 studies in this review, including 14,126 COVID-19 patients and 56,585 non-COVID-19 patients in total. Studies evaluated a total of 67 different laboratory tests. Although we were interested in the diagnotic accuracy of routine tests for COVID-19, the included studies used detection of SARS-CoV-2 infection through RT-PCR as reference standard. There was considerable heterogeneity between tests, threshold values and the settings in which they were applied. For some tests a positive result was defined as a decrease compared to normal vaues, for other tests a positive result was defined as an increase, and for some tests both increase and decrease may have indicated test positivity. None of the studies had either low risk of bias on all domains or low concerns for applicability for all domains. Only three of the tests evaluated had a summary sensitivity and specificity over 50%. These were: increase in interleukin-6, increase in C-reactive protein and lymphocyte count decrease. Blood count Eleven studies evaluated a decrease in white blood cell count, with a median specificity of 93% and a summary sensitivity of 25% (95% CI 8.0% to 27%; very low-certainty evidence). The 15 studies that evaluated an increase in white blood cell count had a lower median specificity and a lower corresponding sensitivity. Four studies evaluated a decrease in neutrophil count. Their median specificity was 93%, corresponding to a summary sensitivity of 10% (95% CI 1.0% to 56%; low-certainty evidence). The 11 studies that evaluated an increase in neutrophil count had a lower median specificity and a lower corresponding sensitivity. The summary sensitivity of an increase in neutrophil percentage (4 studies) was 59% (95% CI 1.0% to 100%) at median specificity (38%; very low-certainty evidence). The summary sensitivity of an increase in monocyte count (4 studies) was 13% (95% CI 6.0% to 26%) at median specificity (73%; very low-certainty evidence). The summary sensitivity of a decrease in lymphocyte count (13 studies) was 64% (95% CI 28% to 89%) at median specificity (53%; low-certainty evidence). Four studies that evaluated a decrease in lymphocyte percentage showed a lower median specificity and lower corresponding sensitivity. The summary sensitivity of a decrease in platelets (4 studies) was 19% (95% CI 10% to 32%) at median specificity (88%; low-certainty evidence). Liver function tests The summary sensitivity of an increase in alanine aminotransferase (9 studies) was 12% (95% CI 3% to 34%) at median specificity (92%; low-certainty evidence). The summary sensitivity of an increase in aspartate aminotransferase (7 studies) was 29% (95% CI 17% to 45%) at median specificity (81%) (low-certainty evidence). The summary sensitivity of a decrease in albumin (4 studies) was 21% (95% CI 3% to 67%) at median specificity (66%; low-certainty evidence). The summary sensitivity of an increase in total bilirubin (4 studies) was 12% (95% CI 3.0% to 34%) at median specificity (92%; very low-certainty evidence). Markers of inflammation The summary sensitivity of an increase in CRP (14 studies) was 66% (95% CI 55% to 75%) at median specificity (44%; very low-certainty evidence). The summary sensitivity of an increase in procalcitonin (6 studies) was 3% (95% CI 1% to 19%) at median specificity (86%; very low-certainty evidence). The summary sensitivity of an increase in IL-6 (four studies) was 73% (95% CI 36% to 93%) at median specificity (58%) (very low-certainty evidence). Other biomarkers The summary sensitivity of an increase in creatine kinase (5 studies) was 11% (95% CI 6% to 19%) at median specificity (94%) (low-certainty evidence). The summary sensitivity of an increase in serum creatinine (four studies) was 7% (95% CI 1% to 37%) at median specificity (91%; low-certainty evidence). The summary sensitivity of an increase in lactate dehydrogenase (4 studies) was 25% (95% CI 15% to 38%) at median specificity (72%; very low-certainty evidence). AUTHORS' CONCLUSIONS: Although these tests give an indication about the general health status of patients and some tests may be specific indicators for inflammatory processes, none of the tests we investigated are useful for accurately ruling in or ruling out COVID-19 on their own. Studies were done in specific hospitalized populations, and future studies should consider non-hospital settings to evaluate how these tests would perform in people with milder symptoms.

The effect of hearing loss configuration on cochlear implantation uptake rates: an Australian experience.

Objective: Recent changes to cochlear implant (CI) candidacy criteria have led to the inclusion of candidates with greater levels of hearing in the contralateral and/or implanted ear. This study assessed the impact of various hearing loss configurations on CI uptake rates (those assessed as eligible for CI, who proceed to CI).Design: Retrospective cohort study.Study sample: Post-lingually deaf adult CI candidates (n = 619) seen at a Western Australian cochlear implant clinic.Results: An overall CI uptake rate of 44% was observed. Hearing loss configuration significantly impacted uptake rates. Uptake rates of 62% for symmetrical hearing loss, 48% for asymmetrical hearing loss (four-frequency average hearing loss (4FAHL) asymmetry ≤60 dB), 25% for highly asymmetrical hearing loss (4FAHL asymmetry >60 dB), 38% for hearing losses eligible for electric-acoustic stimulation, and 22% for individuals with single-sided hearing loss were observed. Hearing loss configuration and age were both significant factors in relation to CI uptake although the impact of age was limited.Conclusion: CI clinics who apply or are considering applying expanded CI candidacy criteria within their practice should be aware that candidates with greater levels of residual hearing in at least the contralateral ear are less likely to proceed to CI.

Investigating the prevalence and impact of device-related problems associated with hearing aid use.

Objective: To explore the prevalence of device-related problems associated with hearing aid use, participants' help-seeking behaviours for these problems, and factors associated with hearing aid problems.Design: A prospective convenience cohort design surveying 413 adult hearing aid users (34-97 years of age) recruited from seven clinics across Australia.Results: Almost all participants (98%) indicated that they were experiencing at least one of the hearing aid problems included on the survey. The number of hearing aid related problems reported by participants ranged from 0 to 25 (of a possible 26), with a mean of 10 problems (SD = 5). The three most reported problems were related to difficulty hearing in noisy environments, hearing in windy environments, and understanding certain voices. Participants had reported less than half (46.33%) of the total problems identified to their clinic (range = 0-100%, mean = 43.40, SD = 13.92). Participants who reported experiencing a greater number of hearing aid problems also reported lower levels of hearing aid benefit, and satisfaction with their hearing aids.Conclusions: The majority of hearing aid owners experience problems with their hearing aids. Addressing these problems would likely contribute to improved hearing aid outcomes.

Hearing aid review appointment: clients' reasons for attendance and non-attendance.

Objective: To investigate hearing aid owners' decisions to attend or not to attend an annual hearing aid review (HAR) appointment. To investigate the possible factors associated with appointment attendance, including age, gender, transportation, travel time, and hearing aid outcomes.Design: A prospective cohort study. Potential participants were notified of their annual HAR appointment in the usual process employed by their clinic. Two months later, potential participants were identified as those who had attended and those who had not attended an appointment.Study sample: One hundred and twenty adult hearing aid users ranging in age from 26 to 100 (M = 74, SD = 11) years recruited from a single hearing clinic in Perth, Western Australia.Results: Factors found to be significantly associated with attendance at an annual HAR appointment included hearing aid funding source (government subsidised), participants valuing the importance and benefit of the appointment, and superior hearing aid outcomes.Conclusions: Within a controlled practice setting, appointment attendance is influenced by some factors modifiable by the clinician, including providing better education about the process and purpose of the HAR appointment. The value of the HAR appointment was emphasised by the positive association between better hearing aid outcomes HAR appointment attendance.

Betahistine for tinnitus.

BACKGROUND: Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy, cognitive behavioural therapy, sound enrichment using ear-level sound generators or hearing aids, and drug therapies to manage co-morbid symptoms such as sleep difficulties, anxiety or depression. As yet, no drug has been approved for tinnitus by a regulatory body. Nonetheless, over 100,000 prescriptions for betahistine are being filled every month in England, and nearly 10% of general practitioners prescribe betahistine for tinnitus. OBJECTIVES: To assess the effects of betahistine in patients with subjective idiopathic tinnitus. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL, via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 July 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) recruiting patients of any age with acute or chronic subjective idiopathic tinnitus were included. We included studies where the intervention involved betahistine and this was compared to placebo, no intervention or education and information. We included all courses of betahistine, regardless of dose regimens or formulations and for any duration of treatment. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes included tinnitus loudness and significant adverse effects (upper gastrointestinal discomfort). Our secondary outcomes included tinnitus symptom severity as measured by the global score on a multi-item tinnitus questionnaire, depressive symptoms, symptoms of generalised anxiety, health-related quality of life, other adverse effects (e.g. headache, drowsiness, allergic skin reactions (pruritis, rashes) and exacerbation of tinnitus) and tinnitus intrusiveness. We used GRADE to assess the quality of evidence for each outcome; this is indicated in italics. MAIN RESULTS: This review included five studies (with a total of 303 to 305 participants) comparing the effects of betahistine with placebo in adults with subjective idiopathic tinnitus. Four studies were parallel-group RCTs and one had a cross-over design. The risk of bias was unclear in all of the included studies.Due to heterogeneity in the outcomes measured and measurement methods used, very limited data pooling was possible. When we pooled the data from two studies for the primary outcome tinnitus loudness, the mean difference on a 0- to 10-point visual analogue scale at one-month follow-up was not significant between betahistine and placebo (-0.16, 95% confidence interval (CI) -1.01 to 0.70; 81 participants) (very low-quality evidence). There were no reports of upper gastrointestinal discomfort (significant adverse effect) in any study.As a secondary outcome, one study found no difference in the change in the Tinnitus Severity Index between betahistine and placebo (mean difference at 12 weeks 0.02, 95% CI -1.05 to 1.09; 50 participants) (moderate-quality evidence). None of the studies reported the other secondary outcomes of changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety, or health-related quality of life as measured by a validated instrument, nor tinnitus intrusiveness.Other adverse effects that were reported were not treatment-related. AUTHORS' CONCLUSIONS: There is an absence of evidence to suggest that betahistine has an effect on subjective idiopathic tinnitus when compared to placebo. The evidence suggests that betahistine is generally well tolerated with a similar risk of adverse effects to placebo treatments. The quality of evidence for the reported outcomes, using GRADE, ranged from moderate to very low.If future research into the effectiveness of betahistine in patients with tinnitus is felt to be warranted, it should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the development of validated, patient-centred outcome measures for research in the field of tinnitus.

Predicting sequential bilateral cochlear implantation performance in postlingually deafened adults; A retrospective cohort study.

OBJECTIVE: To identify which preoperative patient characteristics influence sequential bilateral cochlear implantation performance and to create a statistical model that predicts benefit. DESIGN: Multicentre retrospective cohort study. SETTING: All patients were operated in four academic teaching hospitals in Perth, Australia, and followed up by audiologists of the Ear Science Institute Australia. PARTICIPANTS: A total of 92 postlingually deafened adult patients who had undergone sequential cochlear implantations between 19 June 1990 and 14 March 2016 were included. Patients were excluded if the 12-month follow-up consonant-nucleus-consonant (CNC) phoneme score was missing. MAIN OUTCOME MEASURE: The effect of 18 preoperative factors on the CNC phoneme score in quiet (at 65 dB SPL) with the second cochlear implant (CI2) one year after implantation. RESULTS: Two factors were positively correlated to speech understanding with CI2: Wearing a hearing aid (HA) before receiving CI2 (r = 0.46, P = 0.00) and the maximum CNC phoneme score with the first CI (CI1) (r = 0.21, P = 0.05). Two factors were negatively correlated: the length of hearing loss before CI2 in the second implanted ear (r = -0.25, P = 0.02) and preoperative pure tone average (PTA) (0.5, 1, 2 kHz) before CI2 in the second implanted ear (r = -0.27, P = 0.01). The following model could be created: predicted CNC phoneme score with CI2 (%) = 16 + (44 * HA use before CI2 (yes)) - (0.22 * length of hearing loss before CI2 (years)) + (0.23 * CNC phoneme score with CI1 (%)). Because the effect of HA use before implantation played such a major role, we also created a model after exclusion of the HA factor: Predicted CNC phoneme score with CI2 (%) = 82 - (0.17 * length of hearing loss before CI2 (years)) - (0.27 * PTA in second implanted ear before CI2 (0.5, 1, 2 kHz)) + (0.20 * CNC phoneme score with CI1 (%)). CONCLUSION: Advanced age or a long interval between implantations does not necessarily lead to poor CI2 results. Patients who are successful HA users before CI2, who have a low PTA before CI2, a high CNC phoneme score with CI1 and a limited length of hearing loss before CI2, are likely to be successful CI2 recipients.

Predicting Sequential Cochlear Implantation Performance: A Systematic Review.

This systematic review of the literature reveals which pre-operative factors affect sequential cochlear implantation outcomes in adults. The findings can help health care prof-essionals provide evidence-based advice on the expected benefits from a second cochlear implant (CI). We searched PubMed, EMBASE, and the Cochrane database from November 1977 to August 26, 2017, using the terms "sequential cochlear implantation"; the most frequently cited predictors for unilateral cochlear implantation performance and other potential predictors for sequential implantation outcome; and "speech perception," "localization" as well as synonyms of all of the above. Ten studies were included. The effects of age, duration of hearing loss, time between implantations, preoperative hearing, etiology of hearing loss, hearing aid use and duration of follow-up on sequential cochlear implantation performance were studied. The literature has shown that duration of deafness, age at onset of deafness, etiology of hearing loss, and preoperative speech perception score are (inversely) related to unilateral cochlear implantation outcome in adults. One would expect that these factors would also affect sequential bilateral implantation outcome. However, the best available evidence to date shows that advanced age, a long duration of deafness, or a long interval between implantations should not be considered negative factors when considering sequential bilateral cochlear implantation.

The risk of bias in randomized controlled trials in otorhinolaryngology: hardly any improvement since 1950.

BACKGROUND: Randomized Controlled Trials (RCTs) represent the most valuable study design to evaluate the effectiveness of therapeutic interventions. However, flaws in design, conduct, analysis, and reporting of RCTs can cause the effect of an intervention to be under- or overestimated. These biased RCTs may be included in literature reviews. To make the assessment of Risk of Bias (RoB) consistent and transparent, Cochrane published a RoB tool, with which RoB is assessed per item as "low", "unclear" or "high". Our objective was to provide an overview of RoB assessments of RCTs in otorhinolaryngology over time, and to identify items where improvement is still warranted. METHODS: We retrieved Cochrane reviews in the otorhinolaryngologic research field published in 2012 and 2013. We used all judgments per item as assessed by the review authors of the included RCTs. We evaluated the association between "low RoB" vs. "unclear and high RoB" and the year of publication (time strata: '<1990', '1990-1995', '1996-2000', '2001-2005', '2006-2012') per item using binary logistic regression. RESULTS: We extracted the RoB assessments from 42 Cochrane reviews that had included 402 RCTs (median number of RCTs per review: 7, range 1-40). In total 2,356 items were assessed (mean number of assessed items per RCT: 5.9, standard deviation 1.8). On binary logistic regression, RCTs published in 2006-2012, compared with those published before 1990, were more likely to have a low RoB for two items: random sequence generation (odds ratio 6.09 [95% confidence interval: 3.11-11.95]) and allocation concealment (3.59 [1.87-6.90]). On all other items, there was no significant increase in the proportion of low RoB when comparing RCTs published in 2006-2012 with RCTs published before 1990. CONCLUSION: Although there were some positive developments in the RoB assessments in otorhinolaryngology, a further decrease in RoB is still warranted on several items. Currently, biased RCTs are included in Cochrane reviews and effects of therapeutic interventions can be under- or overestimated, with implications for clinical patient care.

Correlation between subjective and objective hearing tests after unilateral and bilateral cochlear implantation.

BACKGROUND: There are many methods for assessing hearing performance after cochlear implantation. Standard evaluations often encompass objective hearing tests only, while patients' subjective experiences gain importance in today's healthcare. The aim of the current study was to analyze the correlation between subjective (self-reported questionnaires) and objective (speech perception and localization) hearing test results in adult cochlear implant (CI) users. Secondary, the correlation between subjective and objective hearing tests was compared between bilateral and unilateral CI patients. METHODS: Data for this study were prospectively collected as part of a multicentre randomized controlled trial. Thirty-eight postlingually deafened adult patients were randomly allocated to receive either unilateral (n = 19) or bilateral (n = 19) cochlear implantation. We used data gathered after one year of follow-up. We studied the correlation between objectively measured speech perception and localization skills on the one hand and related domains of the Speech, Spatial and Qualities of Hearing Scale (SSQ) and Nijmegen Cochlear Implant Questionnaire (NCIQ) on the other hand. We also compared these correlations between unilateral and bilateral CI users. RESULTS: We found significant weak to moderate negative correlations between the subjective test results (speech domain of the SSQ and the advanced speech perception domain of the NCIQ) and the related objective speech perception in noise test results (r = -0.33 to -0.48). A significant moderate correlation was found between the subjective test results (spatial domain of the SSQ) and the related objective localization test results (r = 0.59). The correlations in the group of bilateral CI patients (r = -0.28 to -0.54) did not differ significantly from the correlations in the group of unilateral CI patients (r = 0.15 to -0.40). CONCLUSIONS: Current objective tests do not fully reflect subjective everyday listening situations. This study elucidates the importance and necessity of questionnaires in the evaluation of cochlear implantation. Therefore, it is advised to evaluate both objective and subjective tests in CI patients on a regular basis. TRIAL REGISTRATION: This trial was registered on March 11, 2009 in the Dutch Trial Register. Trial registration number: NTR1722.

Incorporating ceiling effects during analysis of speech perception data from a paediatric cochlear implant cohort.

OBJECTIVE: To compare speech perception between children with a different age at cochlear implantation. DESIGN: We evaluated speech perception by comparing consonant-vowel-consonant (auditory) (CVC(A)) scores at five-year follow-up of children implanted between 1997 and 2010. The proportion of children from each age-at-implantation group reaching the 95%CI of CVC(A) ceiling scores (>95%) was calculated to identify speech perception differences masked by ceiling effects. STUDY SAMPLE: 54 children implanted between 8 and 36 months. RESULTS: Although ceiling effects occurred, a CVC(A) score difference between age-at-implantation groups was confirmed (H (4) = 30.36; p < 0.001). Outperformance of early (<18 months) compared to later implanted children was demonstrated (p <0.001). A larger proportion of children implanted before 13 months compared to children implanted between 13 and 18 months reached ceiling scores. Logistic regression confirmed that age at implantation predicted whether a child reached a ceiling score. CONCLUSIONS: Ceiling effects can mask thorough delineation of speech perception. However, this study showed long-term speech perception outperformance of early implanted children (<18 months) either including or not accounting for ceiling effects during analysis. Development of long-term assessment tools not affected by ceiling effects is essential to maintain adequate assessment of young implanted infants.

Influence of FDG-PET on primary nodal target volume definition for head and neck carcinomas.

BACKGROUND: The role of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in routine diagnostic staging remains controversial. In case of discordance between FDG-PET and CT, a compromise has to be made between the risk of false positive FDG-PET and the risk of delaying appropriate salvage intervention. Second, with intensity modulated radiation therapy (IMRT), smaller radiation fields allow tissue sparing, but could also lead to more marginal failures. METHODS: We retrospectively studied 283 patients with head and neck carcinoma scheduled for radiotherapy between 2002 and 2010. We analyzed the influence of FDG-PET/CT versus CT alone on defining nodal target volume definition and evaluated its long-term clinical results. Second, the location of nodal recurrences was related to the radiation regional dose distribution. RESULTS: In 92 patients, CT and FDG-PET, performed in mold, showed discordant results. In 33%, nodal staging was altered by FDG-PET. In 24%, FDG-PET also led to an alteration in nodal treatment, including a nodal upstage of 18% and downstage of 6%. In eight of these 92 patients, a regional recurrence occurred. Only two patients had a recurrence in the discordant node on FDG-PET and CT and both received a boost (high dose radiation). CONCLUSION: These results support the complementary value of FDG-PET/CT compared to CT alone in defining nodal target volume definition for radiotherapy of head and neck cancer.

A Systematic Review to Define the Speech and Language Benefit of Early (<12 Months) Pediatric Cochlear Implantation.

OBJECTIVE: This review aimed to evaluate the additional benefit of pediatric cochlear implantation before 12 months of age considering improved speech and language development and auditory performance. MATERIALS AND METHODS: We conducted a search in PubMed, EMBASE and CINAHL databases and included studies comparing groups with different ages at implantation and assessing speech perception and speech production, receptive language and/or auditory performance. We included studies with a high directness of evidence (DoE). RESULTS: We retrieved 3,360 articles. Ten studies with a high DoE were included. Four articles with medium DoE were discussed in addition. Six studies compared infants implanted before 12 months with children implanted between 12 and 24 months. Follow-up ranged from 6 months to 9 years. Cochlear implantation before the age of 2 years is beneficial according to one speech perception score (phonetically balanced kindergarten combined with consonant-nucleus-consonant) but not on Glendonald auditory screening procedure scores. Implantation before 12 months resulted in better speech production (diagnostic evaluation of articulation and phonology and infant-toddler meaningful auditory integration scale), auditory performance (Categories of Auditory Performance-II score) and receptive language scores (2 out of 5; Preschool Language Scale combined with oral and written language skills and Peabody Picture Vocabulary Test). CONCLUSIONS: The current best evidence lacks level 1 evidence studies and consists mainly of cohort studies with a moderate to high risk of bias. Included studies showed consistent evidence that cochlear implantation should be performed early in life, but evidence is inconsistent on all speech and language outcome measures regarding the additional benefit of implantation before the age of 12 months. Long-term follow-up studies are necessary to provide insight on additional benefits of early pediatric cochlear implantation.