Association of Carotid Atherosclerosis With Hearing Loss: A Cross-sectional Analysis of the Atherosclerosis Risk in Communities Study.

Objective: To describe the association between midlife carotid atherosclerosis and late-life hearing loss among participants in the Atherosclerosis Risk in Communities (ARIC) study. Design, Setting, and Participants: For this cross-sectional study and temporal analysis of a cohort within the ongoing ARIC prospective cohort study, participants were recruited from 4 communities in the US. The analysis evaluated information on mean carotid intima-media thickness (cIMT), from visit 1 (1987-1989) to visit 4 (1994-1996), carotid plaque presence at visit 4, and audiometric data from visit 6 (2016-2017). The cIMT measures were calculated from ultrasonography recordings by trained readers at the ARIC Ultrasound Reading Center. At each visit, cIMT was computed as the average of 3 segments: the distal common carotid, the carotid artery bifurcation, and the proximal internal carotid arteries. Presence of carotid plaque was determined based on an abnormal wall thickness, shape, or wall texture. Audiometric 4-frequency pure tone average (PTA) was measured and calculated for the better-hearing ear and modeled as a continuous variable. Linear regression estimated the association between cIMT and carotid plaque with hearing, adjusting for age, sex, race and study center, education level, body mass index (calculated as weight in kilograms divided by height in meters squared), smoking status, hypertension, cholesterol levels, diabetes, and exposure to occupational noise. Missing data (exposure and covariates) were imputed with multiple imputation by chained equations. Data analyses were performed from April 6 to July 13, 2022. Main Outcomes and Measures: Hearing loss assessed using 4-frequency (0.5, 1.0, 2.0, and 4.0 kilohertz) PTA for both ears and carotid plaque at visit 4 and mean cIMT from visit 1 to visit 4. Results: Among a total of 3594 participants (mean [SD] age at visit 4, 59.4 [4.6] years; 2146 [59.7%] female; 819 [22.8%] Black and 2775 [77.2%] White individuals), fully adjusted models indicated that an additional 0.1 mm higher mean cIMT was associated with 0.59 dB (95% CI, 0.17 to 1.02 dB) higher PTA. Compared with participants without carotid plaque, plaque presence was associated with 0.63 dB (95% CI, -0.57 to 1.84 dB) higher PTA. Conclusion and Relevance: The findings of this cross-sectional study with temporal analyses of a cohort with the ongoing ARIC study found that subclinical atherosclerosis in midlife was associated with worse hearing in older adulthood. Prevention and control of carotid atherosclerosis during middle age may positively affect the hearing health of older adults.

Prospective Studies Comparing Structured vs Nonstructured Diagnostic Protocol Evaluations Among Patients With Fever of Unknown Origin: A Systematic Review and Meta-analysis.

Importance: Patients meeting the criteria for fever of unknown origin (FUO) can be evaluated with structured or nonstructured approaches, but the optimal diagnostic method is unresolved. Objective: To analyze differences in diagnostic outcomes among patients undergoing structured or nonstructured diagnostic methods applied to prospective clinical studies. Data Sources: PubMed, Embase, Scopus, and Web of Science databases with librarian-generated query strings for FUO, PUO, fever or pyrexia of unknown origin, clinical trial, and prospective studies identified from January 1, 1997, to March 31, 2021. Study Selection: Prospective studies meeting any adult FUO definition were included. Articles were excluded if patients did not precisely fit any existing adult FUO definition or studies were not classified as prospective. Data Extraction and Synthesis: Abstracted data included years of publication and study period, country, setting (eg, university vs community hospital), defining criteria and category outcome, structured or nonstructured diagnostic protocol evaluation, sex, temperature threshold and measurement, duration of fever and hospitalization before final diagnoses, and contribution of potential diagnostic clues, biochemical and immunological serologic studies, microbiology cultures, histologic analysis, and imaging studies. Structured protocols compared with nonstructured diagnostic methods were analyzed using regression models. Main Outcomes and Measures: Overall diagnostic yield was the primary outcome. Results: Among the 19 prospective trials with 2627 unique patients included in the analysis (range of patient ages, 10-94 years; 21.0%-55.3% female), diagnoses among FUO series varied across and within World Health Organization (WHO) geographic regions. Use of a structured diagnostic protocol was not significantly associated with higher odds of yielding a diagnosis compared with nonstructured protocols in aggregate (odds ratio [OR], 0.98; 95% CI, 0.65-1.49) or between Western Europe (Belgium, France, the Netherlands, and Spain) (OR, 0.95; 95% CI, 0.49-1.86) and Eastern Europe (Turkey and Romania) (OR, 0.83; 95% CI, 0.41-1.69). Despite the limited number of studies in some regions, analyses based on the 6 WHO geographic areas found differences in the diagnostic yield. Western European studies had the lowest percentage of achieving a diagnosis. Southeast Asia led with infections at 49.0%. Noninfectious inflammatory conditions were most prevalent in the Western Pacific region (34.0%), whereas the Eastern Mediterranean region had the highest proportion of oncologic explanations (24.0%). Conclusions and Relevance: In this systematic review and meta-analysis, diagnostic yield varied among WHO regions. Available evidence from prospective studies did not support that structured diagnostic protocols had a significantly better rate of achieving a diagnosis than nonstructured protocols. Clinicians worldwide should incorporate geographical disease prevalence in their evaluation of patients with FUO.

Association of Cigarette Smoking Patterns Over 30 Years With Audiometric Hearing Impairment and Speech-in-Noise Perception: The Atherosclerosis Risk in Communities Study.

IMPORTANCE: The implications of cigarette smoking and smoking cessation for hearing impairment remain unknown. Many studies on this topic have failed to account for attrition among smokers in their findings. OBJECTIVE: To assess the association of cigarette smoking patterns with audiometric and speech-in-noise hearing measures among participants of the Atherosclerosis Risk in Communities Study. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included participants of the Atherosclerosis Risk in Communities Study from 4 US communities. The analysis includes data from visit 1 (1987-1989) through visit 6 (2016-2017); data were analyzed from March 16 through June 25, 2021. Audiometric hearing and speech-in-noise testing was offered to all participants at visit 6. Participants with incomplete audiometric data or missing data for educational level, body mass index, drinking status, a diabetes or hypertension diagnosis, or occupational noise were excluded. In addition, individuals were excluded if they self-reported as having other than Black or White race and ethnicity, or if they self-reported as having Black race or ethnicity and lived in 2 predominantly White communities. MAIN OUTCOMES AND MEASURES: Smoking behavior was classified from visit 1 (1987-1989) to visit 6 (2016-2017) using group-based trajectory modeling based on self-reported smoking status at each clinic visit. Hearing was assessed at visit 6. An audiometric 4-frequency (0.5, 1, 2, 4 kHz) pure-tone average (PTA) was calculated for the better-hearing ear and modeled as a continuous variable. Speech-in-noise perception was assessed via the Quick Speech-in-Noise Test (QuickSIN) and modeled continuously. Attrition during the 30 years of follow-up was addressed by inverse probability of attrition weighting. RESULTS: A total of 3414 participants aged 72 to 94 years (median [IQR] age, 78.8 [76.0-82.9] years; 2032 [59.5%] women) when hearing was measured at visit 6 (2016-2017) were included in the cohort; 766 (22.4%) self-identified as Black and 2648 (77.6%) as White individuals. Study participants were classified into 3 smoking groups based on smoking behavior: never or former smoking at baseline (n = 2911 [85.3%]), quit smoking during the study period (n = 368 [10.8%]), and persistent smoking (n = 135 [4.0%]). In fully adjusted models, persistent smoking vs never or former smoking was associated with an average 2.69 (95% CI, 0.56-4.81) dB higher PTA (worse hearing) and 1.42 (95% CI, -2.29 to -0.56) lower QuickSIN score (worse performance). Associations were stronger when accounting for informative attrition during the study period (3.53 [95% CI, 1.14-5.93] dB higher PTA; 1.46 [95% CI, -2.52 to -0.41] lower QuickSIN scores). Smoking cessation during the study (vs never or former smoking) was not associated with changes in hearing. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, persistent smoking was associated with worse audiometric hearing and speech-in-noise perception. Hearing measures among participants who quit smoking during the study period did not differ from those for never or former smokers, indicating that smoking cessation (as opposed to persistent smoking) may have benefits for hearing health.

Prevalence of Tympanic Membrane Perforations Among Adolescents, Adults, and Older Adults in the United States.

Tympanic membrane (TM) perforations can occur at any age, but limited population-level data are available. Using data from the National Health and Nutrition Examination Survey, we performed a cross-sectional analysis of the prevalence and population estimates for TM perforations among individuals ≥12 years old in the United States. Overall, TM perforations have a prevalence of 2.1% (95% CI, 1.7%-2.6%), corresponding to 5.8 million Americans. Across the life course, older adults have the highest prevalence of TM perforations at 6.1% (95% CI, 4.7%-7.6%), corresponding to nearly 3 million Americans, as opposed to a prevalence of 0.6% (95% CI, 0.3%-0.9%) in adolescents, which equates to 0.2 million Americans. Males and females have a similar prevalence at 2.3% (95% CI, 1.6%-3.0%) among males and 2.0% (95% CI, 1.4%-2.6%) among females. These prevalence and population estimates provide the first US-based population estimates of the burden of TM perforations over the life course.

Association Between Microvascular Retinal Signs and Age-Related Hearing Loss in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

Importance: Given that age-related hearing loss is highly prevalent and treatable, understanding its causes may have implications for disease prevention. Objective: To investigate whether microvascular retinal signs are associated with age-related hearing loss attributable to a hypothesized underlying shared pathologic entity involving microvascular disease. Design, Setting, and Participants: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) is a community-based prospective cohort study of 15 792 men and women aged 45 to 64 years at baseline. The ARIC-NCS participants returned for a fifth clinic visit in 2011-2013 and a sixth clinic visit in 2016-2017. Participants were recruited from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). Participants included a subset of the ARIC-NCS cohort with complete covariate data who underwent retinal fundus photography at visit 5 (2011-2013) and completed hearing assessment at visit 6 (2016-2017) (N = 1458). Overall, 453 participants had diabetes; of those, 68 had retinopathy. Of 1005 participants without diabetes, 42 had retinopathy. Exposures: Microvascular retinal signs included retinopathy, arteriovenous (AV) nicking, and generalized arteriolar narrowing measured using the central retinal arteriolar equivalent (CRAE). Main Outcomes and Measures: Hearing was measured using the better-hearing ear pure-tone average (PTA) of air conduction speech thresholds (0.5, 1, 2, and 4 kHz). Multivariable-adjusted linear and ordered logistic regression was used to estimate the association between microvascular retinal signs and age-related hearing loss to describe the precision of the estimates and provide a plausible range for the true association. Results: After full adjustment among 1458 individuals in the analytic cohort (mean [SD] age, 76.1 [5.0] years [age range, 67-90 years]; 825 women [56.6%]; 285 black [19.5%]), the difference in PTA per dB hearing level in persons with and without retinopathy was 2.21 (95% CI, -0.22 to 4.63), suggesting that retinopathy is associated with poorer hearing, although the width of the 95% CI prevents definitive conclusions about the strength of the observed association. Restricting the analysis to participants without diabetes, the difference in PTA associated with retinopathy was even greater (4.14; 95% CI, 0.10-8.17 dB hearing level), but the large width of the 95% CI prevents definitive conclusions about the association. In analyses quantifying the mean differences in hearing thresholds at individual frequencies by retinopathy status, the estimates trended toward retinopathy being associated, contrary to expectation, with better high-frequency hearing. At 8 kHz, the estimated difference in hearing thresholds in persons with retinopathy vs those without was -4.24 (95% CI, -7.39 to -1.09). Conclusions and Relevance: In this population-based study, an association between the presence of microvascular retinal signs and hearing loss was observed, suggesting that retinopathy may have the potential to identify risk for hearing loss in persons without diabetes. The precision of these estimates is low; therefore, additional epidemiologic studies are needed to better define the degree of microvascular contributions to age-related hearing loss.

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial.

BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.

MVP™ Micro Vascular Plug Systems for the Treatment of Pulmonary Arteriovenous Malformations.

PURPOSE: To describe our institutional experience with MVP™ micro vascular plug systems for the treatment of pulmonary arteriovenous malformations (PAVMs). MATERIALS AND METHODS: We performed a retrospective medical record review of 52 patients with 119 PAVMs treated exclusively with MVP™ systems (69 procedures/153 MVP™ systems) between July 2014 and July 2018. All patients had PAVMs with feeding artery diameters ≥ 2 mm. MVP™ systems were deployed according to physician preference. We collected patient demographic information; procedural data (including size of feeding artery, size and number of embolics used per PAVM, fluoroscopy time, contrast administration), technical success rates, complications, and persistence. Persistence was assessed using computed tomography angiography (CTA) performed 1-3 months and 3-5 years after embolization per clinical protocol. RESULTS: All procedures were technically successful without major complications. Mean feeding artery diameter was 3.3 ± 1.2 mm. Mean fluoroscopy time per procedure and contrast volume administered per procedure were 35 ± 16 min and 217 ± 101 mL, respectively. A mean of 1.3 ± 0.8 MVP™ systems was used per PAVM. There were no instances of persistence during a mean follow-up time of 328 ± 258 days (range 26 to 914 days). CONCLUSIONS: For PAVMs with feeding artery diameters of 2 to 7.9 mm (mean 3.3 ± 1.2 mm), MVP™ systems are safe and effective given their high technical success rates and lack of persistence. Further prospective work will be required to elucidate the advantages and disadvantages of these MVP™ systems for PAVM embolization. LEVEL OF EVIDENCE: Level III.