Opioid Consumption After Discharge From Total Knee and Hip Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Pain is challenging after recovery from total knee arthroplasty (TKA) and total hip arthroplasty (THA) procedures, and patients often receive prescription opioids. However, opioid consumption by patients remains unclear, and unused opioids may lead to risks including misuse and diversion. The objective of this systematic review and meta-analysis was to compare prescription size versus patient-reported consumption of opioids after discharge following TKA and THA. METHODS: PubMed and Embase were systematically searched for publications published between 2015 and 2022 on patient-reported consumption of opioids after TKA and THA. The primary outcome was opioid use in oxycodone 5-mg equivalents. Team members independently reviewed studies for screening, inclusion, data extraction, and risk of bias. RESULTS: Among the 17 included studies (15 TKA and 11 THA), discharge opioid prescribing exceeded consumption for both TKA (88.4 versus 65.0 pills at 6 weeks) and THA (64.0 versus 29.8 pills at 12 weeks). For both TKA and THA, the range of opioids prescribed varied significantly, by 1.6-fold for TKA and 2.8-fold for THA. Most studies reported pain outcomes (89%) and the use of nonopioid medications (72%). Of the 4 studies offering prescribing recommendations, the amounts ranged from 50 to 104 pills for TKA and 30 to 45 pills for THA. CONCLUSIONS: Opioid prescribing exceeds the amount consumed following TKA and THA. These findings serve as a call to action to tailor prescribing guidelines to how much patients actually consume while emphasizing the use of nonopioid medications to better optimize recovery from surgery.

Hidden within a pandemic: how is international funding supporting mental health during COVID-19?

Background: The coronavirus disease 2019 (COVID-19) pandemic is bringing to light the long-neglected area of mental health. Current evidence demonstrates an increase in mental, neurological and substance use conditions globally. Although long-established as a leading cause of disease burden, mental health has been historically grossly underfunded. This analysis seeks to demonstrate the extent to which funding for mental health has been prioritised within the international COVID-19 response. Methods: The authors analysed the development and humanitarian funding through data provided by the International Aid Transparency Initiative. Project-level COVID-19 data from January 2020 to March 2021 were reviewed for mental health relevance. Relevant projects were then classified into categories based on populations of concern for mental health and the degree of COVID-19 involvement. Financial information was assessed through project transaction data in US Dollars. Results: Of the 8319 projects provided, 417 were mental health relevant. Mental health-relevant funding accounted for less than 2% of all COVID-19 development and humanitarian funding. Target populations which received the majority of mental health relevant funding were children and humanitarian populations, and 46% of funding went towards activities which combined COVID-19 responses with general humanitarian actions. Over half of mental health relevant funding was received by ten countries, and ten donor organisations provided almost 90% of funding. Conclusion: This analysis shows that the international donor community is currently falling short in supporting mental health within and beyond the COVID-19 pandemic. As the pandemic continues, sustainable country-led awareness, treatment, and prevention for mental, neurological and substance use conditions must be prioritised.

Chronic Ethanol Metabolism Inhibits Hepatic Mitochondrial Superoxide Dismutase via Lysine Acetylation.

BACKGROUND: Chronic ethanol (EtOH) consumption is a major cause of liver disease worldwide. Oxidative stress is a known consequence of EtOH metabolism and is thought to contribute significantly to alcoholic liver disease (ALD). Therefore, elucidating pathways leading to sustained oxidative stress and downstream redox imbalances may reveal how EtOH consumption leads to ALD. Recent studies suggest that EtOH metabolism impacts mitochondrial antioxidant processes through a number of proteomic alterations, including hyperacetylation of key antioxidant proteins. METHODS: To elucidate mechanisms of EtOH-induced hepatic oxidative stress, we investigate a role for protein hyperacetylation in modulating mitochondrial superoxide dismutase (SOD2) structure and function in a 6-week Lieber-DeCarli murine model of EtOH consumption. Our experimental approach includes immunoblotting immunohistochemistry (IHC), activity assays, mass spectrometry, and in silico modeling. RESULTS: We found that EtOH metabolism significantly increased the acetylation of SOD2 at 2 functionally relevant lysine sites, K68 and K122, resulting in a 40% decrease in enzyme activity while overall SOD2 abundance was unchanged. In vitro studies also reveal which lysine residues are more susceptible to acetylation. IHC analysis demonstrates that SOD2 hyperacetylation occurs near zone 3 within the liver, which is the main EtOH-metabolizing region of the liver. CONCLUSIONS: Overall, the findings presented in this study support a role for EtOH-induced lysine acetylation as an adverse posttranslational modification within the mitochondria that directly impacts SOD2 charge state and activity. Last, the data presented here indicate that protein hyperacetylation may be a major factor contributing to an imbalance in hepatic redox homeostasis due to chronic EtOH metabolism.

Chronic ethanol consumption induces mitochondrial protein acetylation and oxidative stress in the kidney.

In this study, we present the novel findings that chronic ethanol consumption induces mitochondrial protein hyperacetylation in the kidney and correlates with significantly increased renal oxidative stress. A major proteomic footprint of alcoholic liver disease (ALD) is an increase in hepatic mitochondrial protein acetylation. Protein hyperacetylation has been shown to alter enzymatic function of numerous proteins and plays a role in regulating metabolic processes. Renal mitochondrial targets of hyperacetylation include numerous metabolic and antioxidant pathways, such as lipid metabolism, oxidative phosphorylation, and amino acid metabolism, as well as glutathione and thioredoxin pathways. Disruption of protein lysine acetylation has the potential to impair renal function through metabolic dysregulation and decreased antioxidant capacity. Due to a significant elevation in ethanol-mediated renal oxidative stress, we highlight the acetylation of superoxide dismutase, peroxiredoxins, glutathione reductase, and glutathione transferase enzymes. Since oxidative stress is a known factor in ethanol-induced nephrotoxicity, we examined biochemical markers of protein hyperacetylation and oxidative stress. Our results demonstrate increased protein acetylation concurrent with depleted glutathione, altered Cys redox potential, and the presence of 4-HNE protein modifications in our 6-week model of early-stage alcoholic nephrotoxicity. These findings support the hypothesis that ethanol metabolism causes an influx of mitochondrial metabolic substrate, resulting in mitochondrial protein hyperacetylation with the potential to impact mitochondrial metabolic and antioxidant processes.