Cochrane Corner: Hearing aids for mild to moderate hearing loss in adults

This Cochrane Corner features the review entitled “Hearing aids for mild to moderate hearing loss in adults” published in 2017. In their review, Ferguson et al. identified five randomised controlled trials (RCTs) involving 825 participants, with moderate quality of evidence shown for all domains except adverse effects. Results showed a large beneficial effect of hearing aids on hearing-specific health-related quality of life and listening ability, and a small yet significant beneficial effect on overall health related quality of life. Ferguson et al. concluded that according to the available evidence, 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 supports the widespread provision of hearing aids as the first-line clinical management for those seeking help for hearing difficulties

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

SCCRO3 (DCUN1D3) Antagonizes the Neddylation and Oncogenic Activity of SCCRO (DCUN1D1)

The activity of cullin-RING type ubiquitination E3 ligases is regulated by neddylation, a process analogous to ubiquitination that culminates in covalent attachment of the ubiquitin-like protein Nedd8 to cullins. As a component of the E3 for neddylation, SCCRO/DCUN1D1 plays a key regulatory role in neddylation and, consequently, cullin-RING ligase activity. The essential contribution of SCCRO to neddylation is to promote nuclear translocation of the cullin-ROC1 complex. The presence of a myristoyl sequence in SCCRO3, one of four SCCRO paralogues present in humans that localizes to the membrane, raises questions about its function in neddylation. We found that although SCCRO3 binds to CAND1, cullins, and ROC1, it does not efficiently bind to Ubc12, promote cullin neddylation, or conform to the reaction processivity paradigms, suggesting that SCCRO3 does not have E3 activity. Expression of SCCRO3 inhibits SCCRO-promoted neddylation by sequestering cullins to the membrane, thereby blocking its nuclear translocation. Moreover, SCCRO3 inhibits SCCRO transforming activity. The inhibitory effects of SCCRO3 on SCCRO-promoted neddylation and transformation require both an intact myristoyl sequence and PONY domain, confirming that membrane localization and binding to cullins are required for in vivo functions. Taken together, our findings suggest that SCCRO3 functions as a tumor suppressor by antagonizing the neddylation activity of SCCRO

Supplementary Figure 1 from Oncogenic Function of SCCRO5/DCUN1D5 Requires Its Neddylation E3 Activity and Nuclear Localization

PDF file - 918K, A, Schematic representation of domain structures of SCCRO and its paralogues. B, Alignment of PONY domain of SCCRO and its paralogues. SCCRO5 residues critical for binding to neddylation components are shown.</p

Supplementary Figure Legend from Oncogenic Function of SCCRO5/DCUN1D5 Requires Its Neddylation E3 Activity and Nuclear Localization

PDF file - 77K</p

Supplementary Tables 1 - 7 from Oncogenic Function of SCCRO5/DCUN1D5 Requires Its Neddylation E3 Activity and Nuclear Localization

PDF file - 113K, Supplementary Table S1. Oral squamous cell carcinoma- patient and tumor characteristics. Supplementary Table S2. Lung squamous cell carcinoma -patient and tumor characteristics. Supplementary Table S3. Thyroid Carcinoma -patient and tumor characteristics. Supplementary Table S4. Lung neuroendocrine carcinoma -patient and tumor characteristics. Supplementary Table S5. Sequences of the real-time PCR primers for SCCRO5 and housekeeping gene GAPDH (in 5'-3' direction) Supplementary Table S6. Sequences of the DNA mutation analysis primers for SCCRO5 Supplementary Table S7. Sequences of the primers used for SCCRO5 PCR for deletion and mutagenesis.</p