High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews.

BACKGROUND: This overview was originally published in 2017, and is being updated in 2022.  Chronic pain is typically described as pain on most days for at least three months. Chronic non-cancer pain (CNCP) is any chronic pain that is not due to a malignancy. Chronic non-cancer pain in adults is a common and complex clinical issue, for which opioids are prescribed by some physicians for pain management. There are concerns that the use of high doses of opioids for CNCP lacks evidence of effectiveness, and may increase the risk of adverse events. OBJECTIVES: To describe the evidence from Cochrane Reviews and overviews regarding the efficacy and safety of high-dose opioids (defined as 200 mg morphine equivalent or more per day) for CNCP. METHODS: We identified Cochrane Reviews and overviews by searching the Cochrane Database of Systematic Reviews in The Cochrane Library. The date of the last search was 21 July 2022. Two overview authors independently assessed the search results. We planned to analyse data on any opioid agent used at a high dose for two weeks or more for the treatment of CNCP in adults. MAIN RESULTS: We did not identify any reviews or overviews that met the inclusion criteria. The excluded reviews largely reflected low doses or titrated doses, where all doses were analysed as a single group; we were unable to extract any data for high-dose use only. AUTHORS' CONCLUSIONS: There is a critical lack of high-quality evidence, in the form of Cochrane Reviews, about how well high-dose opioids work for the management of CNCP in adults, and regarding the presence and severity of adverse events.  No evidence-based argument can be made on the use of high-dose opioids, i.e. 200 mg morphine equivalent or more daily, in clinical practice. Considering that high-dose opioids have been, and are still being used in clinical practice to treat CNCP, knowing about the efficacy and safety of these higher doses is imperative.

Optimising the integration of technology-enabled solutions to enhance primary mental health care: a service mapping study.

BACKGROUND: Despite the widely acknowledged potential for health information technologies to improve the accessibility, quality and clinical safety of mental health care, implementation of such technologies in services is frequently unsuccessful due to varying consumer, health professional, and service-level factors. The objective of this co-design study was to use process mapping (i.e. service mapping) to illustrate the current consumer journey through primary mental health services, identify barriers to and facilitators of quality mental health care, and highlight potential points at which to integrate the technology-enabled solution to optimise the provision of care based on key service performance indicators. METHODS: Interactive, discussion-based workshops of up to six hours were conducted with representative stakeholders from each participating service, including health professionals, service managers and administrators from Open Arms - Veterans & Families Counselling Service (Sydney), a counselling service for veterans and their families, and five headspace centres in the North Coast Primary Health Network, primary youth mental health services. Service maps were drafted and refined in real time during the workshops. Through both group discussion and the use of post-it notes, participants worked together to evaluate performance indicators (e.g. safety) at each point in the consumer journey (e.g. intake) to indicate points of impact for the technology-enabled solution, reviewing and evaluating differing opinions in order to reach consensus. RESULTS: Participants (n=84 across participating services) created service maps illustrating the current consumer journey through the respective services and highlighting barriers to and facilitators of quality mental health care. By consensus, the technology-enabled solution as facilitated by the InnoWell Platform was noted to enable the early identification of risk, reduce or eliminate lengthy intake processes, enable routine outcome monitoring to revise treatment plans in relation to consumer response, and serve as a personal data record for consumers, driving person-centred, coordinated care. CONCLUSIONS: Service mapping was shown to be an effective methodology to understand the consumer's journey through a service and served to highlight how the co-designed technology-enabled solution can optimise service pathways to improve the accessibility, quality and clinical safety of care relative to key service performance indicators, facilitating the delivery of the right care.

Characteristics and Prognostic Factors for Return to Work in Public Safety Personnel with Work-Related Posttraumatic Stress Injury Undergoing Rehabilitation.

PURPOSE: Public safety personnel (PSP) are at risk of developing posttraumatic stress injury (PTSI) due to exposure to traumatic experiences and accidents. Rehabilitation programs are available, but their success varies. We studied: (1) characteristics of PSP undergoing PTSI rehabilitation in comparison to non-PSP workers; and (2) predictive value of various factors for return to work. Methods A population-based cohort study was conducted using data on injured workers undergoing PTSI rehabilitation. Of the 488 workers included, 131 were PSP. Outcome measures were: (1) return to pre-accident work at rehabilitation discharge; (2) days receiving wage replacement benefits in the year following rehabilitation. Results PSP were mainly employed (90.8%), male (59.5%), paramedics/ambulance workers (58.0%); a minority (43.5%) returned to pre-accident work after rehabilitation. Compared to non-PSP workers, PSP were more likely to initially be diagnosed with psychological injuries (94.7% versus 59.4%, p < 0.001) rather than musculoskeletal injuries. Return to pre-accident work was predicted by shorter injury duration, having a primary mental health diagnosis, working at time of admission, and not having symptoms requiring treatment in a complex rehabilitation program. PSPs were slower to experience full recovery in the year after rehabilitation. Factors predicting fewer benefit days included not having a secondary psychological injury, being employed, and working at time of admission. Conclusions Most PSP did not return to work in full after PTSI rehabilitation. Outcomes are likely to improve by starting treatment earlier and maintaining connections with the workplace.

Random drug and alcohol testing for preventing injury in workers.

BACKGROUND: Drug- and alcohol-related impairment in the workplace has been linked to an increased risk of injury for workers. Randomly testing populations of workers for these substances has become a practice in many jurisdictions, with the intention of reducing the risk of workplace incidents and accidents. Despite the proliferation of random drug and alcohol testing (RDAT), there is currently a lack of consensus about whether it is effective at preventing workplace injury, or improving other non-injury accident outcomes in the work place. OBJECTIVES: To assess the effectiveness of workplace RDAT to prevent injuries and improve non-injury accident outcomes (unplanned events that result in damage or loss of property) in workers compared with no workplace RDAT. SEARCH METHODS: We conducted a systematic literature search to identify eligible published and unpublished studies. The date of the last search was 1 November 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, two other databases, Google Scholar, and three trials registers. We also screened the reference lists of relevant publications known to us. SELECTION CRITERIA: Study designs that were eligible for inclusion in our review included randomised controlled trials (RCTs), cluster-randomised trials (CRTs), interrupted time-series (ITS) studies, and controlled before-after (CBA) studies. Studies needed to evaluate the effectiveness of RDAT in preventing workplace injury or improving other non-injury workplace outcomes. We also considered unpublished data from clinical trial registries. We included employees working in all safety-sensitive occupations, except for commercial drivers, who are the subject of another Cochrane Review. DATA COLLECTION AND ANALYSIS: Independently, two review authors used a data collection form to extract relevant characteristics from the included study. They then analysed a line graph included in the study of the prevalence rate of alcohol violations per year. Independently, the review authors completed a GRADE assessment, as a means of rating the quality of the evidence. MAIN RESULTS: Although our searching originally identified 4198 unique hits, only one study was eligible for inclusion in this review. This was an ITS study that measured the effect of random alcohol testing (RAT) on the test positivity rate of employees of major airlines in the USA from 1995 to 2002. The study included data from 511,745 random alcohol tests, and reported no information about testing for other substances. The rate of positive results was the only outcome of interest reported by the study. The average rate of positive results found by RAT increased from 0.07% to 0.11% when the minimum percentage of workers who underwent RAT annually was reduced from 25% to 10%. Our analyses found this change to be a statistically significant increase (estimated change in level, where the level reflects the average percentage points of positive tests = 0.040, 95% confidence interval 0.005 to 0.075; P = 0.031). Our GRADE assessment, for the observed effect of lower minimum testing percentages associating with a higher rate of positive test results, found the quality of the evidence to be 'very low' across the five GRADE domains. The one included study did not address the following outcomes of interest: fatal injuries; non-fatal injuries; non-injury accidents; absenteeism; and adverse effects associated with RDAT. AUTHORS' CONCLUSIONS: In the aviation industry in the USA, the only setting for which the eligible study reported data, there was a statistically significant increase in the rate of positive RAT results following a reduction in the percentage of workers tested, which we deem to be clinically relevant. This result suggests an inverse relationship between the proportion of positive test results and the rate of testing, which is consistent with a deterrent effect for testing. No data were reported on adverse effects related to RDAT. We could not draw definitive conclusions regarding the effectiveness of RDAT for employees in safety-sensitive occupations (not including commercial driving), or with safety-sensitive job functions. We identified only one eligible study that reflected one industry in one country, was of non-randomised design, and tested only for alcohol, not for drugs or other substances. Our GRADE assessment resulted in a 'very low' rating for the quality of the evidence on the only outcome reported. The paucity of eligible research was a major limitation in our review, and additional studies evaluating the effect of RDAT on safety outcomes are needed.

Co-designing the InnoWell Platform to deliver the right mental health care first time to regional youth.

OBJECTIVE: Building upon earlier research, a person-centred technology-enabled solution (the InnoWell Platform) is being co-designed and implemented into regional youth primary mental health services to improve clinical safety and service quality. DESIGN: Co-design methodologies of service pathway mapping and participatory design workshops as well as usability testing guide the development and implementation of the InnoWell Platform. SETTING AND PARTICIPANTS: headspace centres on the North Coast of New South Wales and their associated communities. MAIN OUTCOME MEASURES: Participation in co-design methodologies, implementation and uptake, identification of youth mental health care needs, and service provision. RESULTS: Nine service pathway mapping (N = 81 participants) and 10 participatory design (N = 48) workshops and usability testing sessions (N = 30) with youth, their supportive others, health professionals, service managers and administrators have been conducted. Four headspace centres have implemented the InnoWell Platform. To date, 120 youth are using the platform and 96 have completed an initial multidimensional assessment. Of these, the majority reported moderate-to-high psychological distress and a quarter reported experiencing high suicidal thoughts and behaviours with subsequent earlier provision of care. Young people have independently commenced recommended online tools and collaborated on clinical care options with their health professionals. CONCLUSIONS: Preliminary findings support co-design methodologies for the development of person-centred technology-enabled solutions embedded within youth primary mental health services in regional Australia. The findings further demonstrate that such solutions may improve clinical safety and service quality, which in turn may facilitate the delivery of the right care, first time!

Birth risks according to maternal height and weight - an analysis of the German Perinatal Survey.

Objective To investigate the variability in the prevalences of selected birth risks in women of different heights and weights. Methods Data from the German Perinatal Survey of 1998-2000 were analyzed: 503,468 cases contributed to our analysis of the prevalences of selected birth risks specified according to maternal weight groups, 502,562 cases contributed to our analysis according to maternal height groups and 43,928 cases contributed to our analysis of birth risks in women with a body mass index (BMI) of 21-23 kg/m2 but different heights and weights. Data analysis was performed using SPSS version 22. Results Some birth risks varied substantially by maternal height in women with a "normal" BMI of 21-23 kg/m2: the prevalence of post-term birth increased from 8.7% in women with a height of 150 cm to 13.5% in 185 cm tall women, the prevalence of preterm birth decreased from 5.9% (150 cm tall women) to 3.1% (185 cm tall women), a pathologic cardiotocography (CTG) or poor fetal heart sounds on auscultation occurred in 19.4% of the 150 cm tall women but only in 9.2% of 185 cm tall women and cephalopelvic disproportion decreased from 12.3% (150 cm tall women) to 1.2% (185 cm tall women). Analyses of women in different body height and weight groups (without restriction of BMI) likewise showed differences in the prevalences of some birth risks. Conclusion Birth risks may vary by height and weight in women with the same, "normal" BMI. BMI should not be the only way by which the impact of maternal height and weight is assessed with regard to perinatal outcomes such as birth risks.

High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews.

BACKGROUND: Chronic pain is typically described as pain on most days for at least three months. Chronic non-cancer pain (CNCP) is any chronic pain that is not due to a malignancy. Chronic non-cancer pain in adults is a common and complex clinical issue where opioids are routinely used for pain management. There are concerns that the use of high doses of opioids for chronic non-cancer pain lacks evidence of effectiveness and may increase the risk of adverse events. OBJECTIVES: To describe the evidence from Cochrane Reviews and Overviews regarding the efficacy and safety of high-dose opioids (here defined as 200 mg morphine equivalent or more per day) for chronic non-cancer pain. METHODS: We identified Cochrane Reviews and Overviews through a search of the Cochrane Database of Systematic Reviews (The Cochrane Library). The date of the last search was 18 April 2017. Two review authors independently assessed the search results. We planned to analyse data on any opioid agent used at high dose for two weeks or more for the treatment of chronic non-cancer pain in adults. MAIN RESULTS: We did not identify any reviews or overviews meeting the inclusion criteria. The excluded reviews largely reflected low doses or titrated doses where all doses were analysed as a single group; no data for high dose only could be extracted. AUTHORS' CONCLUSIONS: There is a critical lack of high-quality evidence regarding how well high-dose opioids work for the management of chronic non-cancer pain in adults, and regarding the presence and severity of adverse events. No evidence-based argument can be made on the use of high-dose opioids, i.e. 200 mg morphine equivalent or more daily, in clinical practice. Trials typically used doses below our cut-off; we need to know the efficacy and harm of higher doses, which are often used in clinical practice.

Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: an overview of Cochrane Reviews.

BACKGROUND: Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'. OBJECTIVES: To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults. METHODS: We searched the Cochrane Database of Systematic Reviews (the Cochrane Library) Issue 3, 2017 on 8 March 2017 to identify all Cochrane Reviews of studies of medium- or long-term opioid use (2 weeks or more) for CNCP in adults aged 18 and over. We assessed the quality of the reviews using the AMSTAR criteria (Assessing the Methodological Quality of Systematic Reviews) as adapted for Cochrane Overviews. We assessed the quality of the evidence for the outcomes using the GRADE framework. MAIN RESULTS: We included a total of 16 reviews in our overview, of which 14 presented unique quantitative data. These 14 Cochrane Reviews investigated 14 different opioid agents that were administered for time periods of two weeks or longer. The longest study was 13 months in duration, with most in the 6- to 16-week range. The quality of the included reviews was high using AMSTAR criteria, with 11 reviews meeting all 10 criteria, and 5 of the reviews meeting 9 out of 10, not scoring a point for either duplicate study selection and data extraction, or searching for articles irrespective of language and publication type. The quality of the evidence for the generic adverse event outcomes according to GRADE ranged from very low to moderate, with risk of bias and imprecision being identified for the following generic adverse event outcomes: any adverse event, any serious adverse event, and withdrawals due to adverse events. A GRADE assessment of the quality of the evidence for specific adverse events led to a downgrading to very low- to moderate-quality evidence due to risk of bias, indirectness, and imprecision.We calculated the equivalent milligrams of morphine per 24 hours for each opioid studied (buprenorphine, codeine, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, levorphanol, methadone, morphine, oxycodone, oxymorphone, tapentadol, tilidine, and tramadol). In the 14 Cochrane Reviews providing unique quantitative data, there were 61 studies with a total of 18,679 randomised participants; 12 of these studies had a cross-over design with two to four arms and a total of 796 participants. Based on the 14 selected Cochrane Reviews, there was a significantly increased risk of experiencing any adverse event with opioids compared to placebo (risk ratio (RR) 1.42, 95% confidence interval (CI) 1.22 to 1.66) as well as with opioids compared to a non-opioid active pharmacological comparator, with a similar risk ratio (RR 1.21, 95% CI 1.10 to 1.33). There was also a significantly increased risk of experiencing a serious adverse event with opioids compared to placebo (RR 2.75, 95% CI 2.06 to 3.67). Furthermore, we found significantly increased risk ratios with opioids compared to placebo for a number of specific adverse events: constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus, and vomiting.There was no data on any of the following prespecified adverse events of interest in any of the included reviews in this overview of Cochrane Reviews: addiction, cognitive dysfunction, depressive symptoms or mood disturbances, hypogonadism or other endocrine dysfunction, respiratory depression, sexual dysfunction, and sleep apnoea or sleep-disordered breathing. We found no data for adverse events analysed by sex or ethnicity. AUTHORS' CONCLUSIONS: A number of adverse events, including serious adverse events, are associated with the medium- and long-term use of opioids for CNCP. The absolute event rate for any adverse event with opioids in trials using a placebo as comparison was 78%, with an absolute event rate of 7.5% for any serious adverse event. Based on the adverse events identified, clinically relevant benefit would need to be clearly demonstrated before long-term use could be considered in people with CNCP in clinical practice. A number of adverse events that we would have expected to occur with opioid use were not reported in the included Cochrane Reviews. Going forward, we recommend more rigorous identification and reporting of all adverse events in randomised controlled trials and systematic reviews on opioid therapy. The absence of data for many adverse events represents a serious limitation of the evidence on opioids. We also recommend extending study follow-up, as a latency of onset may exist for some adverse events.

Mindfulness-based Practices in Workers to Address Mental Health Conditions: A Systematic Review.

The effectiveness of mindfulness techniques in addressing mental health conditions in workers is uncertain. However, it could represent a therapeutic tool for workers presenting with such conditions. Our objective was to assess the effects of mindfulness-based practices for workers diagnosed with mental health conditions. We conducted a systematic review of randomized controlled trials. Participants included were workers with a mental health condition. Interventions included any mindfulness technique, compared to any nonmindfulness interventions. Outcomes were scores on validated psychiatric rating scales. A total of 4,407 records were screened; 202 were included for full-text analysis; 2 studies were included. The first study (Finnes et al., 2017) used Acceptance and Commitment Therapy (ACT) associated or not with Workplace Dialogue Intervention (WDI), compared to treatment as usual. At 9 months follow-up, for the ACT group, depression scores improved marginally (standardized mean difference [SMD]: -0.06, p = 0.021), but anxiety scores were worse (SMD: 0.15, p = 0.036). Changes in mental health outcomes were not statistically significant for the ACT + WDI group. In the second study (Grensman et al., 2018), no statistically significant change in mental health scales has been observed after completion of mindfulness-based cognitive therapy compared to cognitive behavioral therapy. Substantial heterogeneity precluded meta-analysis. This systematic review did not find evidence that mindfulness-based practices provide a durable and substantial improvement of mental health outcomes in workers diagnosed with mental health conditions.

Risk Factors for Developing Concurrent Posttraumatic Stress Injury After Work-Related Musculoskeletal Injury: A Case-Control Study.

OBJECTIVE: This study aimed to study risk factors for developing concurrent posttraumatic stress injury (PTSI) among workers experiencing work-related musculoskeletal injury (MSI). METHODS: A case-control study was conducted using workers' compensation data on injured workers undergoing rehabilitation programs for concurrent MSI and PTSI (cases) and MSI only (controls). A variety of measures known at the time of the compensable injury were entered into logistic regression models. RESULTS: Of the 1948 workers included, 215 had concurrent MSI and PTSI. Concurrent MSI and PTSI were predicted by type of accident (adjusted odds ratio [OR], 25.8), experiencing fracture or dislocation fracture or dislocation (adjusted OR, 3.7), being public safety personnel (adjusted OR, 3.1), and lower level of education (adjusted OR, 1.9). CONCLUSIONS: Experiencing a concurrent PTSI diagnosis with MSI after work-related accident and injury appears related to occupation, type of accident, and educational background.

Technology-Enabled Solutions for Australian Mental Health Services Reform: Impact Evaluation.

BACKGROUND: Health information technologies (HITs) are becoming increasingly recognized for their potential to provide innovative solutions to improve the delivery of mental health services and drive system reforms for better outcomes. OBJECTIVE: This paper describes the baseline results of a study designed to systematically monitor and evaluate the impact of implementing an HIT, namely the InnoWell Platform, into Australian mental health services to facilitate the iterative refinement of the HIT and the service model in which it is embedded to meet the needs of consumers and their supportive others as well as health professionals and service providers. METHODS: Data were collected via web-based surveys, semistructured interviews, and a workshop with staff from the mental health services implementing the InnoWell Platform to systematically monitor and evaluate its impact. Descriptive statistics, Fisher exact tests, and a reliability analysis were used to characterize the findings from the web-based surveys, including variability in the results between the services. Semistructured interviews were coded using a thematic analysis, and workshop data were coded using a basic content analysis. RESULTS: Baseline data were collected from the staff of 3 primary youth mental health services (n=18), a counseling service for veterans and their families (n=23), and a helpline for consumers affected by eating disorders and negative body image issues (n=6). As reported via web-based surveys, staff members across the services consistently agreed or strongly agreed that there was benefit associated with using technology as part of their work (38/47, 81%) and that the InnoWell Platform had the potential to improve outcomes for consumers (27/45, 60%); however, there was less certainty as to whether their consumers' capability to use technology aligned with how the InnoWell Platform would be used as part of their mental health care (11/45, 24% of the participants strongly disagreed or disagreed; 15/45, 33% were neutral; and 19/45, 42% strongly agreed or agreed). During the semistructured interviews (n=3) and workshop, participants consistently indicated that the InnoWell Platform was appropriate for their respective services; however, they questioned whether the services' respective consumers had the digital literacy required to use the technology. Additional potential barriers to implementation included health professionals' digital literacy and service readiness for change. CONCLUSIONS: Despite agreement among participants that HITs have the potential to result in improved outcomes for consumers and services, service readiness for change (eg, existing technology infrastructure and the digital literacy of staff and consumers) was noted to potentially impact the success of implementation, with less than half (20/45, 44%) of the participants indicating that their service was ready to implement new technologies to enhance mental health care. Furthermore, participants reported mixed opinions as to whether it was their responsibility to recommend technology as part of standard care.

Classification of aerosol-generating procedures: a rapid systematic review.

In the context of covid-19, aerosol generating procedures have been highlighted as requiring a higher grade of personal protective equipment. We investigated how official guidance documents and academic publications have classified procedures in terms of whether or not they are aerosol-generating. We performed a rapid systematic review using preferred reporting items for systematic reviews and meta-analyses standards. Guidelines, policy documents and academic papers published in english or french offering guidance on aerosol-generating procedures were eligible. We systematically searched two medical databases (medline, cochrane central) and one public search engine (google) in march and april 2020. Data on how each procedure was classified by each source were extracted. We determined the level of agreement across different guidelines for each procedure group, in terms of its classification as aerosol generating, possibly aerosol-generating, or nonaerosol-generating. 128 documents met our inclusion criteria; they contained 1248 mentions of procedures that we categorised into 39 procedure groups. Procedures classified as aerosol-generating or possibly aerosol-generating by ≥90% of documents included autopsy, surgery/postmortem procedures with high-speed devices, intubation and extubation procedures, bronchoscopy, sputum induction, manual ventilation, airway suctioning, cardiopulmonary resuscitation, tracheostomy and tracheostomy procedures, non-invasive ventilation, high-flow oxygen therapy, breaking closed ventilation systems, nebulised or aerosol therapy, and high frequency oscillatory ventilation. Disagreements existed between sources on some procedure groups, including oral and dental procedures, upper gastrointestinal endoscopy, thoracic surgery and procedures, and nasopharyngeal and oropharyngeal swabbing. There is sufficient evidence of agreement across different international guidelines to classify certain procedure groups as aerosol generating. However, some clinically relevant procedures received surprisingly little mention in our source documents. To reduce dissent on the remainder, we recommend that (a) clinicians define procedures more clearly and specifically, breaking them down into their constituent components where possible; (b) researchers undertake further studies of aerosolisation during these procedures; and (c) guideline-making and policy-making bodies address a wider range of procedures.

Binding to Elongin C inhibits degradation of interacting proteins in yeast.

Elongin C is a highly conserved, low molecular weight protein found in a variety of multiprotein complexes in human, rat, fly, worm, and yeast cells. Among the best characterized of these complexes is a mammalian E3 ligase that targets proteins for ubiquitination and subsequent degradation by the 26 S proteasome. Despite its crucial role as a component of such E3 ligases and other complexes, the specific function of Elongin C is unknown. In yeast, Elongin C is a non-essential gene and there is no obvious phenotype as associated with its absence. We previously reported that in Saccharomyces cerevisiae Elongin C (Elc1) interacts specifically and strongly with a class of proteins loosely defined as stress response proteins. In the present study, we examined the role of yeast Elc1 in the turnover of two of these binding partners, Snf4 and Pcl6. Deletion of Elc1 resulted in decreased steady-state levels of Snf4 and Pcl6 as indicated by Western blot analysis. Northern blot analysis of mRNA prepared from elc1 null and wild type strains revealed no difference in mRNA levels for Snf4 and Pcl6 establishing that the effects of Elc1 are not transcriptionally mediated. Reintroduction of either yeast or human Elongin C into Elc1 null strains abrogated this effect. Taken together, these data document that the levels of Snf4 and Pcl6 are dependent on the presence of Elc1 and that binding to Elc1 inhibits the degradation of these proteins. The results suggest a new function for yeast Elongin C that is distinct from a direct role in targeting proteins for ubiquitination and subsequent proteolysis.