Persistent opioid use after hospital admission due to trauma: a population-based cohort study.

ABSTRACT: Persistent opioid use (POU) is a common marker of harm related to opioid use after trauma. This study determined the incidence and risk factors for POU after hospitalisation due to trauma in New Zealand, among opioid-naïve patients. This was a population-based, retrospective cohort study, using linked data, involving all trauma patients of any age admitted to all NZ hospitals between 2007 and 2019. We included all patients who received opioids after discharge and were considered opioid naïve, defined as not having received opioids or not having a prior diagnosis of opioid-use disorder up to 365 days preceding the discharge date. The primary outcome was the incidence of POU defined as opioid use after discharge between 91 and 365 days. We used a multivariable logistic regression to identify independent risk factors for POU. A total of 177,200 patients were included in this study. Of these, 15.3% (n = 27,060) developed POU based on criteria used for the primary analysis, with sensitivity analyses showing POU incidence ranging from 14.3% to 0.8%. The opioid exposure risk factors associated with POU included switching between different opioids (adjusted odds ratio [aOR] 2.62; 95% confidence interval [CI] 2.51-2.73), prescribed multiple opioids (vs codeine, aOR 1.44; 95% CI 1.37-1.53), slow-release opioid formulations (aOR 1.32; 95% CI 1.26-1.39), and dispensed higher total doses of on the initial discharge prescription (aOR 1.26; 95% CI 1.20-1.33). Overall, 1 in 7 opioid-naïve patients who were exposed to opioids after trauma developed POU. Our findings highlight clinicians should be aware of these factors when continuing opioids on discharge.

Rate and predictors of postoperative opioid use and high opioid exposure after surgery in New Zealand: a retrospective study.

BACKGROUND: Although excessive opioid use is a significant global health issue, there is a lack of literature on the prescribing patterns for postoperative opioid use and exposure after discharge among surgical patients. This study aimed to examine the rate and predictors of opioid dispensing and high opioid exposure after hospital discharge from surgery in New Zealand (NZ) between January 2007 to December 2019. METHODS: This is a retrospective population-based cohort study inclusive of all ages and surgical specialties. Data were obtained from the NZ Ministry of Health's national health databases. RESULTS: 1 781 059 patients were included in the study and 20.9% (n = 371 882) of surgical patients received opioids within 7 days after hospital discharge. From those who were dispensed with opioids after hospital discharge, 36.6% (n = 134 646) had high opioid exposure. Orthopaedic surgery (AOR 6.97; 95% CI 6.82-7.13) and history of opioid use (AOR 3.18; 95% CI 2.86-3.53) increased the odds of postoperative opioid dispensing and high opioid exposure respectively. Severe multi-morbidity burden (AOR 0.76; 95% CI 0.73-0.78) and alcohol misuse (AOR 0.84; 95% CI 0.77-0.93) lowered the odds of postoperative opioid dispensing and high opioid exposure respectively. CONCLUSIONS: Our findings suggest a concerning rate of high opioid exposure among surgical patients after discharge. The predictors for postoperative opioid dispensing and high opioid exposure identified in our study provide insight into opioid prescribing patterns in NZ and inform future postoperative pain management.

Persistent Opioid Use After Hospital Admission From Surgery in New Zealand: A Population-Based Study.

BACKGROUND: Persistent opioid use (POU) is common after surgery and is associated with an increased risk of mortality and morbidity. There have been no population-based studies exploring POU in opioid-naïve surgical patients in New Zealand (NZ). This study aimed to determine the incidence and risk factors for POU in opioid-naïve patients undergoing surgery in all NZ hospitals. METHOD: We included all opioid-naïve patients who underwent surgery without a concomitant trauma diagnosis and received opioids after discharge from any NZ hospital between January 2007 and December 2019. Patients were considered opioid naïve if no opioids had been dispensed to them or if they did not have a prior diagnosis of an opioid-use disorder up to 365 days preceding the index date. The primary outcome was the incidence of POU, defined a priori as opioid use after discharge between 91 and 365 days. We used a multivariable logistic regression to identify risk factors for POU. RESULTS: We identified 1789,407 patients undergoing surgery with no concomitant diagnosis of trauma; 377,144 (21.1%) were dispensed opioids and 260,726 patients were eligible and included in the analysis. Of those included in the final sample, 23,656 (9.1%; 95% confidence interval [CI], 9.0%-9.2%) developed POU. Risk factors related to how opioids were prescribed included: changing to different opioid(s) after discharge (adjusted odds ratio [aOR], 3.21; 95% CI, 3.04-3.38), receiving multiple opioids on discharge (aOR, 1.37; 95% CI, 1.29-1.45), and higher total oral morphine equivalents (>400 mg) (aOR, 1.23; 95% CI, 1.23-1.45). Conversely, patients who were coprescribed nonopioid analgesics on discharge had lower odds of POU (aOR, 0.91; 95% CI, 0.87-0.95). Only small differences were observed between different ethnicities. Other risk factors associated with increased risk of POU included undergoing neurosurgery (aOR, 2.02; 95% CI, 1.83-2.24), higher comorbidity burden (aOR, 1.90; 95% CI, 1.75-2.07), preoperative nonopioid analgesic use (aOR, 1.65; 95% CI, 1.60-1.71), smoking (aOR, 1.44; 95% CI, 1.35-1.54), and preoperative hypnotics use (aOR, 1.35; 95% CI, 1.28-1.42). CONCLUSIONS: Approximately 1 in 11 opioid-naïve patients who were dispensed opioids on surgical discharge, developed POU. Potentially modifiable risk factors for POU, related to how opioids were prescribed included changing opioids after discharge, receiving multiple opioids, and higher total dose of opioids given on discharge. Clinicians should discuss the possibility of developing POU with patients before and after surgery and consider potentially modifiable risk factors for POU when prescribing analgesia on discharge after surgery.

Metagenomic analysis of intestinal microbial function and key genes responsive to acute high-salinity stress in Nile tilapia (Oreochromis niloticus).

The intestinal microbiota is increasingly recognized as playing an important role in aquatic animals. To investigate the functional roles and mechanisms of the intestinal microbial genes/enzymes responding to salinity stress or osmotic pressure in fish, metagenomic analysis was carried out to evaluate the response of intestinal microbiota and especially their functional genes/enzymes from freshwater (the control group) to acute high salinity stress (the treatment group) in Nile tilapia. Our results showed that at the microbial community level, the intestinal microbiota in Nile tilapia generally underwent significant changes in diversity after acute high salinity stress. Among them, the shift in the bacterial community (mainly from Actinobacteria to Proteobacteria) dominated and had a large impact, the fungal community showed a very limited response, and other microbiota, such as phages, likely had a negligible response. At the functional level, the intestinal bacteriadecreased the normal physiological demand and processes, such as those of the digestive system and nervous system, but enhanced energy metabolism. Furthermore, at the gene level, some gene biomarkers, such as glutathione S-transferase, myo-inositol-1(or 4)-monophosphatase, glycine betaine/proline transport system permease protein, and some families of carbohydrate-active enzymes (GT4, GT2), were significantly enriched. However, GH15, GH23 and so on were significantly reduced. Exploring the functional details of the intestinal microbial genes/enzymes that respond to salinity stress in Nile tilapia sheds light on the mechanism of action of the intestinal microbiota with respect to the salinity adaptation of fish.

Bleeding risk of oral anticoagulants in liver cirrhosis.

AIM: The safety of dabigatran is poorly studied in patients with liver cirrhosis and has rarely been compared to warfarin in terms of bleeding risks. METHOD: We undertook a retrospective cohort study across three tertiary centres in Auckland, New Zealand, between 2008 to 2020. Adults 18 years and over and those with a clinically confirmed diagnosis of cirrhosis were included. Data collected included demographic data and clinical characteristics, baseline medication and comorbidities. The primary outcome measure was the incidence of any bleeding event that resulted in hospital admission. RESULTS: Overall, 100 patients were included in this study. A total of 52 patients took warfarin, and 48 took dabigatran. Baseline characteristics for both groups were generally similar. The incidence rate of bleeds for patients taking warfarin was 14.4 per 100 person-years (95% CI, 8.8-23.5) compared to 9.1 per 100 person-years (95% CI, 4.5-18.1) for patients taking dabigatran. The incidence rate ratio comparing dabigatran to warfarin was 0.63 (95% CI, 0.23-1.60), p=0.25. CONCLUSION: Our study found that patients on dabigatran may have a lower bleeding risk than patients taking warfarin, but this was not statistically significant.

Study on the spectroscopy and transition properties of TeCl.

For the first time, the spectroscopy data of TeCl+ ion and the transition data between low excited states are systematically calculated. The potential energy curves of 22 Λ-S states and 51 Ω states are calculated by the internally contracted multiconfiguration interaction and Davidson correction method. By solving the one-dimensional radial Schrödinger equation, the spectroscopy data of Λ-S states and Ω states are obtained. The phenomenon of avoided crossing in Ω state is analyzed in detail, which is mainly concentrated in the region of 20000 cm-1 to 35000 cm-1. The Franck-Condon factors, Einstein coefficients and spontaneous radiative lifetimes of [Formula: see text] transitions are calculated. According to the calculation results, it is preliminarily judged that the direct laser cooling of TeCl+ ion is not feasible.

500 metagenome-assembled microbial genomes from 30 subtropical estuaries in South China.

As a unique geographical transition zone, the estuary is considered as a model environment to decipher the diversity, functions and ecological processes of microbial communities, which play important roles in the global biogeochemical cycle. Here we used surface water metagenomic sequencing datasets to construct metagenome-assembled genomes (MAGs) from 30 subtropical estuaries at a large scale along South China. In total, 500 dereplicated MAGs with completeness ≥ 50% and contamination ≤ 10% were obtained, among which more than one-thirds (n = 207 MAGs) have a completeness ≥ 70%. These MAGs are dominated by taxa assigned to the phylum Proteobacteria (n = 182 MAGs), Bacteroidota (n = 110) and Actinobacteriota (n = 104). These draft genomes can be used to study the diversity, phylogenetic history and metabolic potential of microbiota in the estuary, which should help improve our understanding of the structure and function of these microorganisms and how they evolved and adapted to extreme conditions in the estuarine ecosystem.

Postdischarge opioid use and persistent use after general surgery: A retrospective study.

BACKGROUND: Opioid overprescribing after surgery is a significant public health issue in most developed countries, including New Zealand. However, there is a lack of literature on the patterns and risk factors for postoperative opioid use among general surgical patients in New Zealand. This study aimed to examine opioid use in patients undergoing general surgery at Auckland District Health Board between January and December 2019 and to identify factors associated with opioid use after surgery and persistent opioid use (defined as having filled ≥1 opioid prescription in the 91 to 180 days after surgery). METHODS AND MATERIALS: This is a retrospective cohort study. Data from patients' electronic clinical records and community pharmacy dispensing records were extracted to obtain data on sociodemographics, surgical characteristics, comorbidities, co-prescribed medications, and opioid use. RESULTS: A total of 1,110 patients were included in the study, with 42.4% dispensed an opioid following discharge after surgery. Of opioid-naïve patients who filled opioids after surgery (n = 401), 9.5% became persistent opioid users. Preoperative use of nonopioid analgesics, longer hospital stays, higher operation severity, procedure type, and higher pain scores were positively associated with opioid use, whereas older age was a negative predictor. Longer hospital stays, an initial discharge prescription with high opioid load, and female sex increased the risk of persistent opioid use. Conversely, a higher severity of surgery was associated with lower risk of persistent opioid use. CONCLUSION: The findings suggest that a considerable proportion of patients become persistent opioid users after surgery. The risk factors identified can guide clinicians to prescribe in a manner that reduces opioid-related adverse outcomes and help guide future interventions.

Metagenomic profiles of the resistome in subtropical estuaries: Co-occurrence patterns, indicative genes, and driving factors.

Estuaries are resistome hotspots owing to resistome accumulation and propagation at these locations from surrounding rivers, yet the large-scale biogeographic pattern of resistome, especially biocide and metal resistance genes (BMRGs) and its driving mechanisms in estuarine waters remains to be elucidated. Here, a metagenomics-based approach was firstly used to investigate resistome and mobilome profiles in waters from 30 subtropical estuaries, South China. The Pearl River estuaries had a higher diversity and abundance of antibiotic resistance genes (ARGs), BMRGs, and mobile genetic elements (MGEs) when compared with estuaries from east and west regions. Genes resistant to multiple antibiotics, metals, and biocides were the most abundant gene types in the resistome. The abundance of MGEs (e.g., intI1, IS91, and tnpA) was highly associated with the total abundance of resistance genes, suggesting their utility as potential indicators for quantitative estimations of the resistome contamination. Further, MGEs contributed more than bacterial communities in shaping the resistome in subtropical estuaries. Physicochemical factors (e.g., pH) regulated MGE composition and stochastic assembly, which mediated the co-selection of ARGs and BMRGs via horizontal gene transfer. Our findings have important implications and provide a reference on the management of ARGs and BMRGs in subtropical estuarine ecosystems.

Persistent opioid use and opioid-related harm after hospital admissions for surgery and trauma in New Zealand: a population-based cohort study.

INTRODUCTION: Opioid use has increased globally for the management of chronic non-cancer-related pain. There are concerns regarding the misuse of opioids leading to persistent opioid use and subsequent hospitalisation and deaths in developed countries. Hospital admissions related to surgery or trauma have been identified as contributing to the increasing opioid use internationally. There are minimal data on persistent opioid use and opioid-related harm in New Zealand (NZ), and how hospital admission for surgery or trauma contributes to this. We aim to describe rates and identify predictors of persistent opioid use among opioid-naïve individuals following hospital discharge for surgery or trauma. METHODS AND ANALYSIS: This is a population-based, retrospective cohort study using linked data from national health administrative databases for opioid-naïve patients who have had surgery or trauma in NZ between January 2006 and December 2019. Linked data will be used to identify variables of interest including all types of hospital surgeries in NZ, all trauma hospital admissions, opioid dispensing, comorbidities and sociodemographic variables. The primary outcome of this study will be the prevalence of persistent opioid use. Secondary outcomes will include mortality, opioid-related harms and hospitalisation. We will compare the secondary outcomes between persistent and non-persistent opioid user groups. To compute rates, we will divide the total number of outcome events by total follow-up time. Multivariable logistic regression will be used to identify predictors of persistent opioid use. Multivariable Cox regression models will be used to estimate the risk of opioid-related harms and hospitalisation as well as all-cause mortality among the study cohort in a year following hospital discharge for surgery or trauma. ETHICS AND DISSEMINATION: This study has been approved by the Auckland Health Research Ethics Committee (AHREC- AH1159). Results will be reported in accordance with the Reporting of studies Conducted using Observational Routinely collected health data statement (RECORD).

Current Perspectives on the Role of Nrf2 in 5-Fluorouracil Resistance in Colorectal Cancer.

BACKGROUND: The antimetabolite, 5-Fluorouracil (5-FU), is the only chemotherapeutic drug to significantly improve 12-month survival rates of patients with Colorectal Cancer (CRC). However, resistance to 5-FU is a major obstacle to effective treatment. The mechanism of 5-FU resistance has been discovered but is not fully known. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a master regulator of cellular defense against oxidative and electrophilic stresses, is considered a major factor in 5-FU resistance. OBJECTIVE: The current study was conducted to discuss the role and mechanisms of Nrf2 in 5-FU resistance and to search for medicines or compounds that can reverse Nrf2-mediated 5-FU resistance. METHODS: Literature was obtained by defining specific search terms and searching several databases. RESULTS: Previous study suggested that overactivation of Nrf2 contributed to 5-FU resistance by regulating many cytoprotective genes. Interestingly, several medicines and compounds can repress 5-FU resistance mediated of Nrf2. CONCLUSION: This review describes the major 5-FU-resistance mechanisms of Nrf2 and summarizes the medicines/ compounds that can overcome them.

Systematic review and meta-analysis of oral paracetamol versus combination oral analgesics for acute musculoskeletal injuries.

OBJECTIVE: The aim of this systematic review and meta-analysis was to determine if a combination of analgesics conveys any significant clinical benefit over paracetamol alone in managing acute musculoskeletal injuries. METHODS: Two reviewers independently searched MEDLINE (via PubMed), EMBASE and Cochrane electronic databases. Randomised controlled trials comparing paracetamol with paracetamol plus other oral analgesics in managing acute musculoskeletal injuries (e.g. sprains, contusions) were identified. Outcomes were reduction in pain score, adverse events and need for additional analgesia. Studies were critiqued using the Cochrane Risk of Bias Assessment Tool and data analysed using RevMAN meta-analysis software. RESULTS: Six studies were included (n = 1254). No paediatric studies were identified. Five studies compared paracetamol to paracetamol plus NSAID. One study also included an opioid in the combination group. There was no clinically important difference between groups for reduction in pain score in the first 2 h, 24 h or 72 h. At 2 h the mean difference in reduction in pain score at rest on 100 mm VAS was 0.72 mm (-1.36, 2.79), P = 0.5. On activity it was -1.79 mm (-4.08, 0.49), P = 0.12. The risk of adverse events in ED was -0.00 (-0.04, 0.03). More patients receiving combination therapy required additional analgesia in the first 2 h: -0.03 (-0.06, -0.01), P = 0.01. CONCLUSION: Paracetamol monotherapy is a reasonable first-line analgesic for acute musculoskeletal injuries as combining additional oral agents does not result in any significant additional analgesic effect.

Graft-vs-Host Disease After Liver Transplantation: A Diagnostic and Management Challenge.

A 65-year-old White man underwent deceased donor liver transplant for decompensated liver cirrhosis secondary to alpha-1-antitrypsin deficiency. He developed diarrhea and diffuse maculopapular rash 2 months post-transplant. Skin biopsy revealed necroinflammatory changes related to the superficial dermis. Pancytopenia ensued, complicated by neutropenic sepsis. Chimerism studies confirmed the presence of donor T-lymphocyte macrochimerism (63%). The patient was diagnosed with graft-vs-host disease. After extensive multidisciplinary collaboration, basiliximab was initiated. This resulted in complete symptom resolution and a gradual reduction in T-lymphocyte macrochimerism (12%). The patient was later transitioned to oral ruxolitinib and currently remains in stable condition 16 months after being diagnosed with graft-vs-host disease.

Oral Paracetamol Versus Combination Oral Analgesics for Acute Musculoskeletal Injuries.

STUDY OBJECTIVE: We compare paracetamol with a combination of paracetamol, ibuprofen, and codeine for pain relief in acute minor musculoskeletal injuries. METHODS: This was a prospective, double-blind, randomized, active-controlled, parallel-arm study at an urban tertiary hospital emergency department. Participants were aged 18 to 65 years and had acute (<48 hours) closed limb or trunk injuries with moderate pain (greater than 3/10). A single dose of 1 g of paracetamol, 400 mg of ibuprofen, and 60 mg of codeine was compared with a single dose of 1 g of paracetamol, placebo ibuprofen, and placebo codeine. The minimum detectable difference in pain was taken as 1.3. RESULTS: Baseline characteristics and pain were similar. There were clinically detectable reductions in pain at rest at 60 minutes for paracetamol: -1.6; 95% confidence interval (CI) -2.2 to -1.1); n=59 and the combination -2.0; 95% CI -2.5 to -1; n=59; difference -0.4; 95% CI -1.1 to 0.29; P=.26. At 120 minutes, the reduction in pain was -2.4; 95% CI -3.2 to -1.6 for paracetamol (n=30) and -2.9; 95% CI -3.7 to -2.2 for the combination (n=35); difference -0.5; 95% CI -1.6 to 0.5; P=.32. Rescue analgesia was required by 4 of 59 patients in the paracetamol group and 5 of 60 in the combination group (P>.99). More participants in the combination group had adverse events: 14 of 60 versus 5 of 59 in the paracetamol group, relative risk 2.8; 95% CI 1.1 to 7.2. No adverse events were serious. CONCLUSION: Combining oral paracetamol, ibuprofen, and codeine as the initial treatment for pain associated with acute musculoskeletal injuries was not superior to paracetamol alone for pain reduction at 60 minutes or need for rescue analgesia, with more adverse events in the combination group.

Realizing stable operation of anaerobic ammonia oxidation at low temperatures treating low strength synthetic wastewater.

The low activity of Anammox bacteria at low temperatures and competition from nitrite oxidation bacteria (NOB) when treating low strength wastewater have been major bottlenecks in implementing Anammox in mainstream wastewater treatment. By intermittent high strength feeding (IHSF) and stepwise temperature reduction, stable operation of a granular Anammox reactor was realized at low temperatures (down to 15°C) for 28days when treating low strength synthetic wastewater. The nitrogen loading rate reached 1.23-1.34kgN/m3/day, and the total nitrogen removal rate reached 0.71-0.98kgN/m3/day. The IHSF enriched the Anammox sludge in high strength cycles and compensated for sludge loss in low strength cycles, and the high concentration of ammonium in high strength cycles inhibited NOB. The 16SrRNA gene sequencing results revealed that Candidatus Kuenenia was predominant in the reactor at low temperatures.