Predictors of persistent opioid use in Australian primary care: A retrospective cohort study, 2018-2022.

OBJECTIVE: To examine the predictors of persistent opioid use ('persistence') in people initiating opioids for non-cancer pain in Australian primary care. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: People prescribed opioid analgesics between 2018-2022, identified through the Population Level Analysis and Reporting (POLAR) database. METHODS: Persistence was defined as receiving opioid prescriptions for at least 90 days with a gap of less than 60 days between subsequent prescriptions. Multivariable logistic regression was used to examine the predictors of persistent opioid use. RESULTS: The sample consisted of 343,023 people initiating opioids for non-cancer pain; of these, 16,527 (4.8%) developed persistent opioid use. Predictors of persistence included older age (≥75 vs 15-44 years: Adjusted odds ratio: 1.67, 95% CI: 1.58-1.78), concessional beneficiary status (1.78, 1.71-1.86), diagnosis of substance use disorder (1.44, 1.22-1.71) and chronic pain (2.05, 1.85-2.27), initiation of opioid therapy with buprenorphine (1.95, 1.73-2.20) and long-acting opioids (2.07, 1.90-2.25), provision of higher quantity of opioids prescribed at initiation (total OME of ≥ 750mg vs < 100mg: 7.75, 6.89-8.72), provision of repeat/refill opioid prescriptions at initiation (2.94, 2.77-3.12), and prescription of gabapentinoids (1.59, 1.50-1.68), benzodiazepines (1.43, 1.38-1.50) and z-drugs (e.g., zopiclone, zolpidem; 1.61, 1.46-1.78). CONCLUSIONS: These findings add to the limited evidence of individual-level factors associated with persistent opioid use. Further research is needed to understand the clinical outcomes of persistent opioid use in people with these risk factors to support the safe and effective prescribing of opioids.

Factors Associated with an Increased Risk of Opioid Misuse Among Patients with Non-Cancer Pain in Malaysian Pain Clinic Settings.

This study examined the factors associated with a high risk of opioid misuse among patients receiving opioid treatment for their non-cancer pain in Malaysian pain clinics. The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), a validated instrument for predicting the risk of aberrant drug-related behaviors, were used as a proxy to indicate risk of opioid misuse. Data analysis was stratified into high-risk and low-risk patient groups. Patient factors assessed included pain intensity, pain interference with daily activities, and health-related quality of life. Prescription opioid exposure was examined via patient medical and prescription records review. Among the 61 patients recruited, 62.3% scored ≥18 on the SOAPP-R, which indicates a high risk for opioid misuse. Factors associated with a high risk of opioid misuse were found to be high level of pain interference with daily activities, poorer mental health, and younger age. High-risk patients were found to be prescribed a lower mean daily opioid dose of <20 mg/day compared to low-risk patients (20-49 mg/day). This highlights the need for further research to distinguish aberrant drug-related behaviors due to inadequate pain management from that of actual prescription opioid misuse among non-cancer pain patients attending pain clinics.

Recommendations for managing adults with chronic non-cancer pain in primary care: A systematic clinical guideline review.

RATIONALE: Chronic non-cancer pain (CNCP) is a leading driver of disability. Primary care clinicians treat most patients with CNCP. Yet, they are often unable to identify appropriate pain treatments, mainly due to concerns about the safety and effectiveness of available medications. Clinical practice guidelines (CPGs) can be useful tools to guide primary care clinicians in selecting pain treatments based on the best available evidence. OBJECTIVES: To undertake a systematic review of CPGs that address the management of adults with CNCP, regardless of underlying condition type, in primary care. METHOD: We systematically reviewed and synthesised current CPGs for managing adults with CNCP in primary care (2013-2023). We followed a stepwise systematic process to synthesise key CPG recommendations: extracted and analysed each recommendation, synthesised by compiling similar recommendations using a thematic analysis approach, and assessed the strength of CPG recommendations to create a final, unified set of recommendations. We focused on identifying CPGs containing recommendations on the following topics: (a) opioid pain management, (b) non-opioid pharmacological pain management, (c) non-pharmacological pain management, and (d) patient-centred communication around pain management, prevention, and organisation of care. RESULTS: We included 13 CPGs, 8 of which focused solely on use of opioids, emphasising the lack of long-term effectiveness and safety concerns, being mainly based on the expert consensus. As an exception, high-quality evidence recommended referring patients with suspected opioid use disorder to specialist addiction services for medication-assisted treatment. Recommendations for non-opioid pain management were often contradictory and based on the expert consensus. Patient-centred pain management combined with exercise-based interventions and psychological therapies are appropriate strategies for managing patients with CNCP. CONCLUSION: Most CPGs focused on opioid management, with contradictory recommendations for non-opioid management based on low-quality evidence. Additional research is needed to strengthen the evidence for using non-opioid and non-pharmacological interventions to manage patients with CNCP.

Overall and cause-specific mortality among patients diagnosed with gastric precancerous lesions in Sweden between 1979 and 2014: an observational cohort study.

BACKGROUND: The Correa's cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa's cascade are scarce. METHODS: We compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979-2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison. RESULTS: A total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08-1.14) for the normal mucosa group to 1.54 (95% CI 1.46-1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa's cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for "infectious diseases and parasitic diseases", "respiratory system diseases", and "digestive system disease", when using the normal mucosa group as reference. CONCLUSIONS: Increased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted.

Prospect and Challenges of Volatile Organic Compound Breath Testing in Non-Cancer Gastrointestinal Disorders.

Breath analysis, despite being an overlooked biomatrix, has a rich history in disease diagnosis. However, volatile organic compounds (VOCs) have yet to establish themselves as clinically validated biomarkers for specific diseases. As focusing solely on late-stage or malignant disease biomarkers may have limited relevance in clinical practice, the objective of this review is to explore the potential of VOC breath tests for the diagnosis of non-cancer diseases: (1) Precancerous conditions like gastro-esophageal reflux disease (GERD) and Barrett's esophagus (BE), where breath tests can complement endoscopic screening; (2) endoluminal diseases associated with autoinflammation and dysbiosis, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease, which currently rely on biopsy and symptom-based diagnosis; (3) chronic liver diseases like cirrhosis, hepatic encephalopathy, and non-alcoholic fatty liver disease, which lack non-invasive diagnostic tools for disease progression monitoring and prognostic assessment. A literature search was conducted through EMBASE, MEDLINE, and Cochrane databases, leading to an overview of 24 studies. The characteristics of these studies, including analytical platforms, disorder type and stage, group size, and performance evaluation parameters for diagnostic tests are discussed. Furthermore, how VOCs can be utilized as non-invasive diagnostic tools to complement existing gold standards is explored. By refining study designs, sampling procedures, and comparing VOCs in urine and blood, we can gain a deeper understanding of the metabolic pathways underlying VOCs. This will establish breath analysis as an effective non-invasive method for differential diagnosis and disease monitoring.

Non-cancer-related Deaths in Cancer Survivors: A Nationwide Population-Based Study in Japan.

BACKGROUND: Advancements in cancer care have improved survivorship, potentially leading to changes in mortality causes. This study aimed to investigate the causes of death among cancer survivors, specially focusing on non-cancer-related mortality. METHODS: This nationwide population-based cohort study analyzed the causes of death based on the time since cancer diagnosis using data from the National Cancer Registry in Japan between January 2016 and December 2019. Non-cancer-related deaths were identified, and mortality risks associated with non-cancer diseases were compared to those of the Japanese general population using standardized mortality ratios (SMRs) with 95% confidence intervals (CIs). Follow-up period was up to 4 years after cancer diagnosis. RESULTS: A total of 3,990,661 patients (45.8%, women) were included in the analysis, yielding 6,237,269 person-years of follow-up. Of these, 1,001,857 (25.1%) patients died during the study period. Cancer-related and non-cancer-related causes accounted for 86.6% and 13.4% of deaths, respectively. The proportion of non-cancer-related deaths increased from 10.2% at 6 months to 31.6% at 4 years after cancer diagnosis. Heart disease (21.8%), cerebrovascular disease (9.8%), and pneumonia (9.1%) were the leading cause of non-cancer-related deaths: The SMRs for these diseases were 2.69 (95% CI, 2.66-2.72), 2.07 (95% CI, 2.03-2.10), and 2.41 (95% CI, 2.36-2.45), respectively. The SMR for suicide was 1.81 (95% CI, 1.74-1.89); however, it lost significance in males and females 2 and 2.5 years after cancer diagnosis, respectively. CONCLUSIONS: The proportion of non-cancer-related deaths among cancer patients has increased over time, emphasizing the need to manage cancer and its comorbidities carefully.

Determinants of successful opioid deprescribing: Insights from French pain physicians-A qualitative study.

BACKGROUND: Long-term use of opioids does not result in significant clinical improvement and has shown more adverse than beneficial effects in chronic pain conditions. When opioids cause more adverse effects than benefits for the patient, it may be necessary to initiate a process of deprescribing. AIM: To explore the perceptions of French pain physicians regarding the process of opioid deprescribing in patients experiencing chronic non-cancer and to generate an understanding of the barriers and levers to the deprescribing process. METHODS: We conducted a multicentric observational study with qualitative approach. Individual semi-structured interviews exploring pain physicians' perceptions, beliefs, and representations to assess the determinants of opioid deprescribing with an interview guide were used. After checking the transcripts, an inductive and independent thematic analysis of the interviews was to extract meaningful themes from the dataset. RESULTS: Twelve pain physicians were interviewed. The main obstacles to deprescribing revolved around patient-specific attributes, characteristics of the opioids themselves, and limitations within the current healthcare system, that hinder optimal patient management. Conversely, patient motivation and education, recourse to hospitalization in a Pain Department with multidisciplinary care, follow-up by the general practitioner, and training and information dissemination among patients and clinicians emerged as facilitative elements for opioid deprescribing. CONCLUSION: This study underscores the needs to improve the training of healthcare professionals, the effective communication of pertinent information to patients, and the establishment of a therapeutic partnership with the patient. It is therefore essential to carry out the deprescribing process in a collaborative and interprofessional manner, encompassing both pharmaceutical and non-pharmaceutical strategies.

Utilizing topological indices in QSPR modeling to identify non-cancer medications with potential anti-cancer properties: a promising strategy for drug repurposing.

The exploration of non-cancer medications with potential anti-cancer activity offers a promising avenue for drug repurposing, accelerating the development of new oncological therapies. This study employs Quantitative Structure-Property Relationship (QSPR) modeling to identify and predict the anti-cancer efficacy of various non-cancer drugs, utilizing topological indices as key descriptors. Topological indices, which capture the molecular structure's geometric and topological characteristics, provide critical insights into the pharmacological interactions relevant to anti-cancer activity. By analyzing a comprehensive dataset of non-cancer medications, this research establishes robust QSPR models that correlate topological indices with anti-cancer activity. The models demonstrate significant predictive power, highlighting several non-cancer drugs with potential anti-cancer properties. Further, we will use linear, quadratic and logarithmic regression to understand the structures of anti-cancer drugs and strengthen our ability to manipulate the molecular structures. The findings underscore the utility of topological indices in drug repurposing strategies and pave the way for further experimental validation and clinical trials. This integrative approach enhances our understanding of drug action mechanisms and offers a cost-effective strategy for expanding the repertoire of anti-cancer agents.

Estimating cure and risk of death from other causes of cancer patients: EUROCARE-6 data on head & neck, colorectal, and breast cancers.

BACKGROUND: To estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population. METHODS: A new modelling approach, that corrects for patients' extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40-79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries. FINDINGS: Young male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4. INTERPRETATION: Not considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients' quality of life.

Use of CYP2D6 substrates and inhibitors during pain management with analgesic opioids: Drug-drug interactions that lead to lack of analgesic effectiveness.

BACKGROUND: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes. MATERIALS AND METHODS: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded. RESULTS: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present. CONCLUSION: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.

Pain in people seeking and receiving opioid agonist treatment: A systematic review and meta-analysis of prevalence and correlates.

BACKGROUND AND AIMS: People with opioid use disorder (OUD) commonly experience pain including chronic pain. Despite the high prevalence, few studies have systematically examined the prevalence and correlates of pain among people seeking or receiving opioid agonist treatment (OAT) for OUD. This review aimed to determine the prevalence of pain in this population globally, and estimate the association between chronic pain and other demographic and clinical characteristics. METHODS: Electronic searches were conducted in three databases (Medline, Embase and PsycINFO) from the inception until October 2022. Eligible studies reported prevalence rates of current and/or chronic pain. Meta-analyses examining the main prevalence estimates were conducted by Stata SE 18.0, and comorbid clinical conditions were analysed by Review Manager 5.4. RESULTS: Fifty-six studies (n participants = 35 267) from sixty-seven publications were included. Prevalence estimates of current and chronic pain were reported in 27 (48.2%) and 40 studies (71.4%), respectively. Most studies were conducted in North America (71.4%, n = 40) and used cross-sectional designs (64.3%, n = 36). Meta-analyses revealed a pooled prevalence of 60.0% (95% confidence interval [CI]: 52.0-68.0) for current pain and 44.0% [95% CI: 40.0-49.0] for chronic pain. Chronic pain was positively associated with older age (mean deviation of mean age: 2.39 years, 95% CI: 1.40-3.37; I2 = 43%), unemployment (odds ratio [OR] = 0.57, 95% CI: 0.42-0.76; I2 = 78%), more severe mental health symptoms (e.g. more severe depression (standardised mean difference [SMD] of mean scores: 0.45, 95% CI: 0.20-0.70; I2 = 48%) and anxiety symptoms (SMD: 0.52, 95% CI: 0.17-0.88; I2 = 67%), and hepatitis C (OR = 1.41, 95% CI: 1.03-1.94; I2 = 0%). No association was observed between chronic pain and the onset and type of OAT, geographic location, study design, survey year, participant age or use of specific pain assessment tools. CONCLUSIONS: There appears to be a high prevalence of pain among people seeking or receiving opioid agonist treatment for opioid use disorder compared with the general population, with positive associations for older age, unemployment, hepatitis C and the severity of some mental health symptoms.

A Kernelized Classification Approach for Cancer Recognition Using Markovian Analysis of DNA Structure Patterns as Feature Mining.

Nucleotide-based molecules called DNA and RNA are essential for several biological processes that affect both normal and cancerous cells. They contain the critical genetic material needed for normal cell growth and functioning. The DNA structure patterns that make up the genetic code affect cells' growth, behavior, and control. Different DNA structure patterns indicate different physiological effects in the cell. Knowledge of these patterns is necessary to identify the molecular origins of cancer and other disorders. Analyzing these patterns can help in the early detection of diseases, which is essential for the effectiveness of cancer research and therapy. The novelty of this study is to examine the patterns of dinucleotide structure in many genomic regions, including the non-coding region sequence (N-CDS), coding region sequence (CDS), and whole raw DNA sequence (W.R. sequence). It provides an in-depth discussion of dinucleotide patterns related to these diverse genetic environments and contains malignant and non-malignant DNA sequences. The Markovian modeling that predicts dinucleotide probabilities also reduces feature complexity and minimizes computational costs compared to the approaches of Kernelized Logistic Regression (KLR) and Support Vector Machine (SVM). This technique is effectively evaluated in essential case studies, as indicated by accuracy metrics and 10-fold cross-validation. The classifier and feature reduction, which are generated by Markovian probability, operate well together and can help predict cancer. Our findings successfully distinguish DNA sequences related to cancer from those diagnostics of non-cancerous diseases by analyzing the W.R. DNA sequence as well as its CDS and N-CDS regions.

Groundwater in the coastal areas of Ghana: Quality and associated health risks.

Self-supply water sources, particularly groundwater sources, play key roles in the water supply ecosystem of developing countries. Recent studies indicate that groundwater sources in coastal communities in Ghana are under threat from improper waste management practices, seawater intrusion and atmospheric aerosol deposition. In this study, Water Quality Index (WQI) and Nemerow's Pollution Index (NPI) were employed to assess groundwater quality in four coastal communities of Ghana. The health risks associated with metal pollution of groundwater were investigated using incremental life cancer risk and hazard quotient. pH of groundwater in all the studied communities were acidic during the rainy season. Electrical conductivity ranged from 0.44 to 2.61 mS/cm in the rainy season and from 0.43 to 2.45 mS/cm in the dry season for the four studied locations. Results also showed brackish conditions and mineralization of groundwater in Winneba, Accra, and Keta. Mean nitrate concentrations in Winneba and Accra were higher than the WHO standards for both the rainy and the dry season. Arsenic was higher than the acceptable level in Accra and Keta during the dry season, while iron was higher than the acceptable levels in Accra in both the rainy and dry seasons. Principal Component Analyses showed that Pb, As, and Fe had the highest loading in the first component in Essiama, while PO4 3-and Pb had the highest loading in the second component in Accra. WQI showed that the quality of groundwater in all the studied communities ranged from marginal to poor indicating that groundwater in the coastal communities often or usually departs from desirable quality. NPI revealed that NO3- , As, and Fe contribute to groundwater deterioration. Health risk assessment showed that As posed a high cancer risk in Accra and potential cancer risk in Essiama, Winneba, and Keta during the dry season. As also posed potential cancer risk in Accra during the rainy season. Non-cancer health risk was observed for As in Accra and Keta. The findings of this study suggest urgent regulations and monitoring strategies to improve groundwater quality in the coastal communities of Ghana.

A Conceptual Analysis of Opioid Use Disorder in Chronic Noncancer Pain Using Rodger's Evolutionary Approach.

OBJECTIVE: This study aims to examine the complex nature of opioid use disorder (OUD) in chronic noncancer pain (CNCP) by exploring its antecedents, attributes, consequences, and interrelated concepts. DESIGN: A systematic literature review was conducted to gather relevant studies published between 2015 and 2022, utilizing the CINAHL, MEDLINE, PsycINFO, and PubMed databases. DATA SOURCES: The selected databases provided a comprehensive range of articles related to OUD in CNCP, ensuring a comprehensive topic analysis. METHODS: Twenty-two articles meeting the inclusion criteria were included in the analysis. These articles were critically reviewed and analyzed to identify key themes and concepts related to OUD in CNCP. RESULTS: The findings of this study shed light on the multifaceted aspects of OUD in CNCP, including its antecedents, such as goals of physical function improvement, prescription of opioids for CNCP, social influences, and mental health dynamics. The attributes of OUD in CNCP were identified as chronic pain, noncancer pain, opioid use, misuse, and abuse. OUD's consequences in CNCP include impaired functioning, increased health risks, psychological distress, social challenges, and economic burden. CONCLUSION: Understanding the complexity of OUD in CNCP is crucial for improving patient outcomes. Collaborative efforts among healthcare systems, regulatory bodies, and professional organizations are needed to develop policies promoting safe and effective pain management while mitigating risks associated with opioid use in CNCP. IMPLICATIONS FOR PRACTICE: Implementing policy recommendations derived from this study enhances care and outcomes for individuals with CNCP. By addressing complex issues of OUD in CNCP and adopting evidence-based practices, healthcare providers can optimize pain management and promote well-being in CNCP patients.

Public Perceptions of Opioid Use for Chronic Non-Cancer Pain.

Background: Chronic non-cancer pain affects 20% of Americans. This is significantly impacted by the ongoing opioid crisis and reduced opioid dispensing. Public perceptions additionally shape pain management strategies. Purpose: This study explores public attitudes toward prescription opioids for chronic non-cancer pain. We aim to understand how public attitudes are influenced by the evolving opioid crisis and shifting opioid use patterns. Methods: In Michigan, 823 adults participated in a Qualtrics survey on attitudes toward nonmedical and medical prescription opioid use. Multivariable logistic regression was performed to identify factors associated with beliefs that doctors prescribe opioids for too long (Model 1) and chronic pain patients should transition to alternative treatments (Model 2). Results: About half (49.4%) of respondents believed doctors keep patients on prescription opioids for too long, while two-thirds (65.7%) agreed chronic pain patients should be tapered off medications. Knowing someone who misused opioids and perceptions of substance use (e.g. perceived risk of prescription opioid misuse, stigma toward chronic pain patients, perceived prevalence of prescription opioid misuse, and awareness of fentanyl) were associated with greater odds of believing doctors keep patients on opioids too long. Demographics (age and education), substance use histories and perceptions (e.g. perceived risk and stigma) were associated with greater odds of believing patients should be tapered off their medication. Conclusions: These findings inform strategies to correct public misperceptions, emphasizing the importance of personal experience, perceived risks, and stigmatization of chronic pain patients. This insight can guide effective pain management for those with chronic non-cancer pain.

Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond.

tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs originating from mature or precursor tRNAs (pre-tRNA), typically spanning 14 to 30 nt. The Mitogen-activated protein kinases (MAPK) pathway orchestrates cellular responses, influencing proliferation, differentiation, apoptosis, and transformation. tsRNAs influence the expression of the MAPK signaling pathway by targeting specific proteins within the pathway. Presently, four MAPK-linked tsRNAs have implications in gastric cancer (GC) and high-grade serous ovarian cancer (HGSOC). Notably, tRF-Glu-TTC-027 and tRF-Val-CAC-016 modulate MAPK-related protein expression, encompassing p38, Myc, ERK, CyclinD1, CyclinB, and c-Myc, hindering GC progression via MAPK pathway inhibition. Moreover, tRF-24-V29K9UV3IU and tRF-03357 remain unexplored in specific mechanisms. KEGG analysis posits varied tsRNAs in MAPK pathway modulation for diverse non-cancer maladies. Notably, high tRF-36-F900BY4D84KRIME and tRF-23-87R8WP9IY expression relates to varicose vein (VV) risk. Elevated tiRNA-Gly-GCC-001, tRF-Gly-GCC-012, tRF-Gly-GCC-013, and tRF-Gly-GCC-016 target spinal cord injury (SCI)-related brain-derived neurotrophic factor (BDNF), influencing MAPK expression. tRF-Gly-CCC-039 associates with diabetes foot sustained healing, while tRF-5014a inhibits autophagy-linked ATG5 in diabetic cardiomyopathy (DCM). Additionally, tsRNA-14783 influences keloid formation by regulating M2 macrophage polarization. Upregulation of tRF-Arg-ACG-007 and downregulation of tRF-Ser-GCT-008 are associated with diabetes. tsRNA-04002 alleviates Intervertebral disk degeneration (IDD) by targeting PRKCA. tsRNA-21109 alleviates Systemic lupus erythematosus (SLE) by inhibiting macrophage M1 polarization. The upregulated tiNA-Gly-GCC-002 and the downregulated tRF-Ala-AGC-010, tRF-Gln-CTG-005 and tRF-Leu-AAG-001 may be involved in the pathogenesis of Lupus nephritis (LN) by affecting the expression of MAPK pathway. Downregulation of tsRNA-1018, tsRNA-3045b, tsRNA-5021a and tsRNA-1020 affected the expression of MAPK pathway, thereby improving Acute lung injury (ALI). This review comprehensively dissects tsRNA roles in MAPK signaling across cancers and other diseases, illuminating a novel avenue for translational medical exploration.

Two-year Opioid Prescription Trends in Local Sanitary Agency Naples 3 South, Campania Region, Italy. Descriptive Analyses and AI-based Translational Perspectives.

Aims: This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed. Methods: From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD). Results: The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( p < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs. Conclusion: Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.

Exposure to benzene, toluene, ethylbenzene, and xylene (BTEX) at Nigeria's petrol stations: a review of current status, challenges and future directions.

Introduction: In Nigeria, because of increasing population, urbanization, industrialization, and auto-mobilization, petrol is the most everyday non-edible commodity, and it is the leading petroleum product traded at the proliferating Nigeria's petrol stations (NPSs). However, because of inadequate occupational health and safety (OHS) regulatory measures, working at NPSs exposes petrol station workers (PSWs) to a large amount of hazardous benzene, toluene, ethylbenzene, and xylene (BTEX) compounds. Methods: Studies on BTEX exposures among Nigerian PSWs are scarce. Thus, constraints in quantifying the health risks of BTEX limit stakeholders' ability to design practical risk assessment and risk control strategies. This paper reviews studies on the OHS of Nigerian PSWs at the NPSs. Results: Although knowledge, attitude, and practices on OHS in NPSs vary from one Nigeria's study setting to another, generally, safety practices, awareness about hazards and personal protective equipment (PPE), and the use of PPE among PSWs fell below expectations. Additionally, air quality at NPSs was poor, with a high content of BTEX and levels of carbon monoxide, hydrogen sulfide, particulate matter, and formaldehyde higher than the World Health Organization guideline limits. Discussion: Currently, regulatory bodies' effectiveness and accountability in safeguarding OHS at NPSs leave much to be desired. Understanding the OHS of NPSs would inform future initiatives, policies, and regulations that would promote the health and safety of workers at NPSs. However, further studies need to be conducted to describe the vulnerability of PSWs and other Nigerians who are occupationally exposed to BTEX pollution. More importantly, controlling air pollution from hazardous air pollutants like BTEX is an essential component of OHS and integral to attaining the Sustainable Development Goals (SDG) 3, 7, and 11.