Hearing Benefit in Middle Ear Reconstructive Surgery: A Comparative Study of the Current Methods

INTRODUCTION: Discharging ear and deafness are perpetual source of misery to humankind. Chronic suppurative otitis media is found to be the single major cause of conductive deafness manifesting in 66.3% of cases. The other causes being trauma, otosclerosis, congenital malformations, neoplastic causes etc. Auditory sensation is one of the vital sensations for existence. Deafness upsets the tranquility of life. When such a great vital sensation is lost, life naturally loses its charm. In last 50 years, various researches have been carried out for repair of ossicular chain defects alone or those associated with tympanic membrane perforations. A number of materials have been used with varying results. Right from Hall and Rytzer of 1957 till today, several pioneers have revolutionized the outlook of ossiculoplasty. Several materials have been used for ossiculoplasty. Some of the materials are autograft/homograft ossicles, autograft/homograft cartilage, teflon, hydroxyapatite, titanium, gold, bioglass etc. The goal of otologists performing middle ear surgery to correct conductive hearing loss is to improve hearing as well as to provide a functional benefit to the patient. Unilateral conductive hearing loss is associated with various disabilities including difficulty in sound localization and in hearing and understanding speech. Traditionally, otologists have reported the results of middle ear surgery as the closure of the air - bone gap or the reduction in air conduction thresholds. The closure of the air-bone gap refers to improvement of the air conduction thresholds (involving conductive and sensorineural components) to the level of the bone conduction thresholds (sensorineural component). While these provide a measure of the technical success of the operation, they may not always translate into real life benefit for the patient. Hence standardization of results of treatment should be by a method based on subjective perception which benefits patients in real life. Other methods have been used to evaluate the effectiveness of middle ear surgery including questionnaires that evaluate a patient's subjective benefit from surgery. Using questionnaires to evaluate benefit is complicated by the fact that both surgeons and patients want to believe that the operation has succeeded. The two most common methods found in the otologic literature to evaluate benefit from middle ear surgery are the Belfast 15/30 dB rule of thumb and the Glasgow benefit plot. These methods facilitates the assessment of subjective benefit as well as objective achievement, we have employed these two most common methods to estimate patient benefit from middle ear surgery in our study. AIMS AND OBJECTIVES: 1. To compare two methods of predicting the level of hearing benefit following middle ear surgery, namely Glasgow benefit plot and Belfast 15/30 dB rule of Thumb. 2. To correlate hearing benefit as measured by using the above methods with patients' self assessment of his/her hearing status 3. To analyze the differences in hearing improvement by various ossiculoplasties like incus interposition, tragal/ conchal cartilage and autograft malleus. 4. To compare the success rates with surgery on dry and wet ears. 5. To compare success rates with cavity mastoidectomy cases versus those without cavity. MATERIALS AND METHODS: Sixty patients undergoing middle ear surgery were selected at random with no age or sex bias. Only patients with conductive hearing loss were selected. The minimum age was 11 years and maximum age was 48 years. Those cases requiring myringoplasty were excluded from the study. Any allergic or septic focus was ruled out preoperatively. Cases with bilateral ear disease were also taken up and revision cases were also subjected to surgery on 7 occassions. Both wet and dry ears were taken up. Patients were admitted one day before the surgery. Mastoid shaving and local preparation were done in the ward. All cases were operated under general anaesthesia. The types of surgery included in the study were mastoid exploration, tympanoplasty and ossiculoplasty. Apart from a detailed case history, patients were assessed clinically with the help of otoscopy, tuning fork tests, pure tone audiometry, free field hearing tests, X-ray Mastoids and CT Temporal bone were done where applicable. A detailed questionnaire was used (separately to be filled in by the patient and the close first relative of the patient) pre and post operatively, to assess the level of hearing. Patients were followed post operatively for 3 & 6 months. RESULTS AND OBSERVATIONS: There were 38 males and 22 females. Age range was from 11-48 years. The younger patients were more aware of their hearing loss and consisted of 76.6 % of all the patients. The commonest disease was CSOM - tubotympanic (14 cases) and atticoantral (46 cases). Group 1 : Unilateral hearing impairment, asymmetric threshold 12 patients were included in this group. All had pure tone average above 30 dB in one ear; all had interaural difference of more than 10 dB. Preoperative self assessment of hearing loss by patients : Patients presented with varying degrees of subjective hearing impairment, such as diminished hearing from a distance, in group conversation, on telephone, discharge and diminished hearing. Post operatively: Hearing from operated and non-operated ear was same in 6 patients (3 patients had inter aural difference of 12, 12 & 18 dB but claimed symmetric hearing). Group 2 : Bilateral hearing impairment, asymmetric threshold. 40 patients were included in this group and 37 patients had pure tone averages above 30 dB in both ears. 29 patients had inter aural difference of more than 10dB. Patients claimed significant benefit post operatively. Hearing from operated and non-operated ear was same in 33 patients. The prediction by both methods in this group was 100%. 19 patients fell in category 'c' and claimed significant benefit. Group 3 : Bilateral hearing impairment - symmetric threshold 8 patients were included in this group. Pure tone average was less than 30 dB in six cases and interaural difference within 10 dB in 2 cases and 12,12,15,16,25,28,26 dB in 6 patients. They had significant benefit following surgery and claimed that the operated ear was the better hearing ear. As per audiometry, 2 patients fell in category 'c' and claimed significant benefit. As per subjective benefit all these patients claimed significant benefit. Comparing the same with 15/30 dB rule of thumb as per audiometry, the overall positive predictive value was 80% and as per subjective benefit 84%. Applying Z test for significance of difference between the predictive values by pure Tone Audiometry and subjective benefit in both the methods, the difference is not significant since Z is <1.96 at 95% confidence interval. 10 out of 12 patients (83%) in Group I had no difficulty in localizing sound, as only one ear is actually sufficient to localize sound. According to Browning GG (1993), minor head movement can achieve the necessary variation in speech perception level. In Group 3, 8 patients had bilateral symmetric hearing loss as per pure tone audiometry. Pure tone averages in the 0.5,1,2 kHz were same in both ears. This correlates with observations of G.G.Browning (1993), audiometric tests do not measure all aspects of hearing; hence the ear being operated upon should be as per patient's choice. CONCLUSION: 1. The overall success rate of ossiculoplasty in the present study is 80%. 2. In this study its found that Glasgow benefit plot is more sophisticated, graphical, providing a good visual impression whereas Belfast Rule of thumb is easy and simple to use, but, it suffers from the disadvantages of 'all or none phenomenon' with no place for marginal benefit. 3. Hearing improvement with Incus transposition is better followed by tragal and conchal cartilage ossiculoplasty, Homograft Malleus (in descending order). 4. Hearing improvement is better when minimal ossicular disruption is present. (All present > Incus absent > M-I-> M-I-S-) 5. Hearing improvement is better when cholesteatoma is absent (when compared to cholesteatoma cases). 6. Hearing improvement is better with dry ears. 7. Hearing improvement is better when cavity mastoidectomy was not done (when compared to cavity mastoidectomy cases.) 8. Fresh cases do better than revision cases. 9. Cases without granulations do better than those with granulations

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62-0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce progression of chronic kidney disease and the risk of cardiovascular morbidity and mortality in a wide range of patients. However, their effects on kidney disease progression in some patients with chronic kidney disease are unclear because few clinical kidney outcomes occurred among such patients in the completed trials. In particular, some guidelines stratify their level of recommendation about who should be treated with SGLT2 inhibitors based on diabetes status and albuminuria. We aimed to assess the effects of empagliflozin on progression of chronic kidney disease both overall and among specific types of participants in the EMPA-KIDNEY trial. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA), and included individuals aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 20 to less than 45 mL/min per 1·73 m2, or with an eGFR of 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher. We explored the effects of 10 mg oral empagliflozin once daily versus placebo on the annualised rate of change in estimated glomerular filtration rate (eGFR slope), a tertiary outcome. We studied the acute slope (from randomisation to 2 months) and chronic slope (from 2 months onwards) separately, using shared parameter models to estimate the latter. Analyses were done in all randomly assigned participants by intention to treat. EMPA-KIDNEY is registered at ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and then followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroups of eGFR included 2282 (34·5%) participants with an eGFR of less than 30 mL/min per 1·73 m2, 2928 (44·3%) with an eGFR of 30 to less than 45 mL/min per 1·73 m2, and 1399 (21·2%) with an eGFR 45 mL/min per 1·73 m2 or higher. Prespecified subgroups of uACR included 1328 (20·1%) with a uACR of less than 30 mg/g, 1864 (28·2%) with a uACR of 30 to 300 mg/g, and 3417 (51·7%) with a uACR of more than 300 mg/g. Overall, allocation to empagliflozin caused an acute 2·12 mL/min per 1·73 m2 (95% CI 1·83-2·41) reduction in eGFR, equivalent to a 6% (5-6) dip in the first 2 months. After this, it halved the chronic slope from -2·75 to -1·37 mL/min per 1·73 m2 per year (relative difference 50%, 95% CI 42-58). The absolute and relative benefits of empagliflozin on the magnitude of the chronic slope varied significantly depending on diabetes status and baseline levels of eGFR and uACR. In particular, the absolute difference in chronic slopes was lower in patients with lower baseline uACR, but because this group progressed more slowly than those with higher uACR, this translated to a larger relative difference in chronic slopes in this group (86% [36-136] reduction in the chronic slope among those with baseline uACR <30 mg/g compared with a 29% [19-38] reduction for those with baseline uACR ≥2000 mg/g; ptrend<0·0001). Interpretation: Empagliflozin slowed the rate of progression of chronic kidney disease among all types of participant in the EMPA-KIDNEY trial, including those with little albuminuria. Albuminuria alone should not be used to determine whether to treat with an SGLT2 inhibitor. Funding: Boehringer Ingelheim and Eli Lilly