Popping pills in youth elite sports - fact or fiction? A 36-week prospective cohort study of analgesic use in 1195 youth elite athletes and student controls.

OBJECTIVE: To investigate analgesic use in a cohort of Danish youth elite athletes, and compare weekly analgesic use over 36 weeks to student controls. We also investigated and compared reasons for analgesic use and types of analgesics used. DESIGN: Prospective cohort study. METHODS: 690 youth elite athletes (44% females) and 505 student controls (59% females) (age 15-20 years) provided weekly reports on analgesic use over 36 weeks. We asked about number of days with analgesic use, reasons for use, and types of analgesics used. Prevalence and frequency of analgesic use was compared between youth elite athletes and student controls using mixed effects logistic regression and mixed effects Poisson regression models. Reasons for and types of analgesics used was compared between groups using Chi-square tests. Subgroup analyses were performed, stratified by sex. RESULTS: Overall, athletes had lower odds of analgesic use (OR 0.78, 95% CI 0.64 to 0.95) compared with student controls. The overall usage rate was similar between the groups (IRR 1.04, 95% CI 0.99 to 1.11). Subgroup analyses suggested no statistically significant differences in the odds of analgesic use. Significantly more athletes reported using analgesics to prevent or treat pain or injury in relation to sports participation and to use topical gels compared with student controls. CONCLUSION: Participating in youth elite sports was associated with lower odds of analgesic use compared to student controls, but usage rate was similar between the groups. Reasons for use and types of analgesics use differed between athletes and student controls.

Analgesic efficacy of stellate ganglion block in head and neck cancer pain: A case series.

Patients with head and neck cancer (HNC) have ongoing pain but Stellate ganglion block which is a sympatholytic block may be a viable therapy for treating it. The data were retrospectively collected from five histopathologically confirmed HNC patients who had completed chemotherapy and radiation doses. Stellate ganglion block was given to these patients and was subsequently monitored for 3 months to assess pain alleviation and overall satisfaction. Over a 3-month period, there was a decrease in the pain levels with a better quality of life so the stellate ganglion block can be a promising modality for reducing the pain of HNC.

Relationship between intraoperative requirement for anesthetics and postoperative analgesic consumption in laparoscopic colectomy: a randomized controlled double-blinded study.

BACKGROUND: This study investigated the relationship between intraoperative requirement for an inhalational anesthetic (sevoflurane) or an opioid (remifentanil) and postoperative analgesic consumption. METHODS: The study included 200 adult patients undergoing elective laparoscopic colectomy. In the sevoflurane group, the effect-site concentration of remifentanil was fixed at 1.0 ng/ml, while the inspiratory sevoflurane concentration was adjusted to maintain an appropriate anesthetic depth. In the remifentanil group, the end-expiratory sevoflurane concentration was fixed at 1.0 vol.%, and the remifentanil concentration was adjusted. Pain scores and cumulative postoperative analgesic consumptions were evaluated at 2, 6, 24, and 48 h after surgery. RESULTS: Average end-tidal concentration of sevoflurane and effect-site concentration of remifentanil were 2.0 ± 0.4 vol.% and 3.9 ± 1.4 ng/ml in the sevoflurane and remifentanil groups, respectively. Cumulative postoperative analgesic consumption at 48 h postoperatively was 55 ± 26 ml in the sevoflurane group and 57 ± 33 ml in the remifentanil group. In the remifentanil group, the postoperative cumulative analgesic consumptions at 2 and 6 h were positively correlated with intraoperative remifentanil requirements (2 h: r = 0.36, P < 0.001; 6 h: r = 0.38, P < 0.001). However, there was no significant correlation in the sevoflurane group (r = 0.04, P = 0.691). CONCLUSIONS: The amount of intraoperative requirement of short acting opioid, remifentanil, is correlated with postoperative analgesic consumption within postoperative 6 h. It may be contributed by the development of acute opioid tolerance. However, intraoperative sevoflurane requirement had no effect on postoperative analgesic consumption.

Opioid-free anesthesia using a combination of ketamine and dexmedetomidine in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Opioids administered as bolus doses or continuous infusions are widely used for major and daycare surgeries. Opioid-free anesthesia is multimodal anesthesia and analgesia that does not use opioids, benefiting patients from opioid-related adverse effects. We compared the postoperative analgesic requirements of patients scheduled for elective laparoscopic cholecystectomy under opioid-free and opioid-based anesthesia. METHODS: Study included 88 patients aged 18-60 years with American Society of Anesthesiologists physical status 1 and 2 who underwent elective laparoscopic cholecystectomy. Participants were randomly divided into two groups with 44 in each. The opioid-free group was administered an intravenous bolus of ketamine and dexmedetomidine, whereas fentanyl was used in opioid group. Primary outcome was to compare the total amount of fentanyl consumed by both groups during 6 h postoperative period. Episodes of postoperative nausea and vomiting (PONV) and vital signs were noted throughout the postoperative period to analyze the secondary outcomes. RESULTS: Both groups had similar demographic characteristics. The opioid-free group required lesser analgesia within the first 2 h (61.4 ± 17.4 vs. 79.0 ± 19.4 of fentanyl, P < 0.001), which was statistically significant. However, fentanyl consumption was comparable between the groups at 6 h (152 ± 28.2 vs. 164 ± 33.4, P = 0.061). Compared with 4.5% of the participants in the opioid-free group, 34% of those in the opioid-based group developed moderate PONV. CONCLUSIONS: Opioid-free anesthesia in patients undergoing laparoscopic cholecystectomy reduced the requirement of analgesia in first two-hour postoperative period and was associated with decreased PONV.

[Pain therapy in urology-overview of current S3 guideline recommendations]. / Schmerztherapie in der Urologie ­ Überblick zu aktuellen Empfehlungen der S3-Leitlinen.

Dealing efficiently with patients suffering from pain is a central medical task. Pain, as an important function in developmental physiology, warns against damage to the body caused by external noxious agents as well as internal malfunctions and requires special attention in modern medicine. Peri- and postoperative pain is known to have a negative influence on postoperative convalescence. Treatment of tumor-related pain represents another relevant challenge in uro-oncology and palliative medicine. The updated guideline on perioperative pain therapy and palliative medicine for patients with incurable diseases or cancer is dedicated to these two topics.

Advances in the Synthesis of Biologically Active Quaternary Ammonium Compounds.

This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review highlights examples of quaternary ammonium compounds exhibiting activity against protozoa and herbicidal effects, as well as analgesic and anesthetic derivatives. The article also embraces the quaternary-ammonium-containing cholinesterase inhibitors and muscle relaxants. QACs, marked by their inherent permanent charge, also find widespread usage across diverse domains such as fabric softeners, hair conditioners, detergents, and disinfectants. The effectiveness of QACs hinges greatly on finding the right equilibrium between hydrophilicity and lipophilicity. The ideal length of the alkyl chain varies according to the unique structure of each QAC and its biological settings. It is expected that this review will provide comprehensive data for medicinal and industrial chemists to design and develop novel QAC-based products.

Alcohol Use Disorder and Chronic Pain: An Overlooked Epidemic.

Alcohol use disorder (AUD) and chronic pain disorders are pervasive, multifaceted medical conditions that often co-occur. However, their comorbidity is often overlooked, despite its prevalence and clinical relevance. Individuals with AUD are more likely to experience chronic pain than the general population. Conversely, individuals with chronic pain commonly alleviate their pain with alcohol, which may escalate into AUD. This narrative review discusses the intricate relationship between AUD and chronic pain. Based on the literature available, the authors present a theoretical model explaining the reciprocal relationship between AUD and chronic pain across alcohol intoxication and withdrawal. They propose that the use of alcohol for analgesia rapidly gives way to acute tolerance, triggering the need for higher levels of alcohol consumption. Attempts at abstinence lead to alcohol withdrawal syndrome and hyperalgesia, increasing the risk of relapse. Chronic neurobiological changes lead to preoccupation with pain and cravings for alcohol, further entrenching both conditions. To stimulate research in this area, the authors review methodologies to improve the assessment of pain in AUD studies, including self-report and psychophysical methods. Further, they discuss pharmacotherapies and psychotherapies that may target both conditions, potentially improving both AUD and chronic pain outcomes simultaneously. Finally, the authors emphasize the need to manage both conditions concurrently, and encourage both the scientific community and clinicians to ensure that these intertwined conditions are not overlooked given their clinical significance.

Long-Term Use of Rimegepant 75 mg for the Acute Treatment of Migraine is Associated with a Reduction in the Utilization of Select Analgesics and Antiemetics.

Purpose: To examine use of concomitant analgesics and antiemetics during treatment with rimegepant in adults with migraine. Patients and Methods: This was a post hoc analysis of a long-term, open-label, safety study in adults with a history of 2-14 moderate or severe migraine attacks per month. Participants self-administered rimegepant 75 mg (1) up to once daily as needed (PRN) for 52 weeks or (2) every other day plus PRN (EOD+PRN) for 12 weeks. The PRN cohort was further divided based on baseline attack frequency, with PRN (2-8) and PRN (9-14) cohorts having a history of 2-8 or 9-14 attacks per month, respectively. Use of select analgesics and antiemetics was analyzed during a 30-day pre-treatment observation period (OP) and during rimegepant treatment. Results: Overall, 1800 rimegepant-treated participants (PRN n = 1514, EOD+PRN n = 286) were included in the analysis. Select analgesics or antiemetics were used by 80.1% of participants during the OP. Among 1441 participants using analgesics or antiemetics during the OP, the proportion who did not use any analgesics or antiemetics following initiation of rimegepant treatment increased during weeks 1-4 (36.9%), 5-8 (52.6%), and 9-12 (56.5%). The mean number of days per month using analgesics or antiemetics was also significantly reduced over time in all cohorts beginning at weeks 1-4 (P < 0.001 vs OP). This pattern of reduced analgesic or antiemetic use was consistent for all rimegepant cohorts, but was most pronounced in the EOD+PRN cohort in which 74.8% of participants reported ≥50% reduction in analgesic/antiemetic days at weeks 9-12. Reduction in use was maintained over time, with 61.3% of participants not using any analgesics or antiemetics during weeks 49-52 of PRN treatment. Conclusion: Long-term treatment with oral rimegepant was associated with reduced analgesic and antiemetic use. Clinicaltrials.gov: NCT03266588.

Associations between over-the-counter analgesics usage and symptoms of anxiety and depression in adolescents: a network analysis.

BACKGROUND: The use of over-the-counter analgesics (OTCA) is common among adolescents and has been linked with increased symptoms of anxiety and depression. However, little is known about which specific symptoms are most strongly connected to OTCA usage. The current study assessed which anxiety and depression symptoms were most closely associated with OTCA usage in a large sample of adolescents and examined whether this differed across genders. METHOD: The present study was based on data from 626,581 participants from the Ungdata survey in Norway. Associations between OTCA and anxiety and depression symptoms were examined using network analysis. Non-regularized partial-correlation networks were constructed to estimate the conditional dependent relations between the use of OTCA and symptoms while controlling for pain. Gender-specific networks were created for comparison. RESULTS: OTCA usage was associated with most symptoms, even after controlling for pain, with the strongest associations with "sleep problems", "stiff or tense", "everything is a struggle" and "suddenly scared". There were some gender differences, showing that "sleep problems" and "hopeless" were more strongly related to OTCA usage in females, whereas "stiff or tense" was more strongly related to OTCA usage in males. CONCLUSION: Overall, the somatic symptoms of anxiety and depression displayed the strongest associations with OTCA usage. When examining the gender-specific networks, both showed similar trends, although males exhibited slightly stronger associations between OTCA usage and somatic symptoms.

Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. MATERIAL AND METHODS: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. RESULTS: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. CONCLUSIONS: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

The use of opioids nine months after surgery for Crohn's disease - a nationwide cohort study.

BACKGROUND: The risk of chronic opioid use after surgery for Crohn's disease (CD) is not known. AIM: The aim of this study is to examine the chronic opioid use after surgery according to age at time of surgery and to opioid use prior to surgery. METHODS: This nationwide cohort study included patients with a first surgery for CD (January 1, 1996 through 2021). We examined prescribed opioids 9 months after surgery and estimated adjusted odds ratios (OR) for chronic opioid use in elderly (≥60 years), adults (≥40 and <60 years), and young adults (≥18 and <40 years) according to opioid use prior to surgery. Chronic opioid use was defined as prescriptions in at least two of three consecutive quarters. RESULTS: A total of 797 patients had surgery as elderly, 1603 as adults, and 2786 as young adults. Across all age groups, 18%-38% received opioid prescriptions throughout 9 months after surgery, if opioids were prescribed prior to surgery. If opioids were not prescribed prior to surgery, the corresponding proportions were 2%-5%. If patients were prescribed opioids (≥1) prior to surgery, the adjusted ORs (95% CIs) for their chronic use after surgery in elderly, adults, and young adults were 10.37 (6.77-15.88), 10.48 (7.74-14.19), and 6.55 (4.93-8.72), respectively. CONCLUSION: Clinicians should be aware that in patients with a need for opioids before surgery, the surgery may not change the need for opioids. Future research should examine effective analgesic strategies that help minimise opioid use in this population.

Opioid analgesic exposure during the first trimester of pregnancy and the risk of major congenital malformations in infants: a systematic review and meta-analysis†.

BACKGROUND: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta-analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. METHODS: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first-trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non-Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random-effects meta-analysis. RESULTS: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98-1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96-1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92-1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38-5.16) and cleft palate (relative risk 1.57, 95%CI 0.48-5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05-1.36) following codeine exposure. CONCLUSIONS: Although the meta-analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field.

Long-term use of prescription opioids for non-cancer pain and mortality: a population-based, propensity-weighted cohort study.

OBJECTIVE: The objective of this study was to identify factors associated with long-term opioid use and to assess the association between long-term use and death. STUDY DESIGN: Retrospective cohort study combining several population-wide databases and covering a population of five million inhabitants, including all adults who were initiated on opioid treatment from 2014 to 2018 for non-cancer pain. METHODS: We used logistic regression models to identify factors associated with chronic opioid use and carried out survival analyses using multivariable Cox regression modelling for all-cause mortality during follow-up using inverse probability of treatment weighting (IPTW) and propensity scores based on the probability of using opioids chronically. RESULTS: Among 760,006 patients, 82,423 (10.85%) used opioids for 90 days or more after initiation. Initial therapy characteristics associated with higher risk for long-term use were initiating with long- and short-acting opioids (when compared to tramadol, odds ratio [OR]: 2.63, 95% confidence interval [CI]: 2.57, 2.69 and OR: 1.60, 95%CI: 1.46, 1.76, respectively), using higher daily doses (when compared to 50 morphine milligramme equivalent [MME] or less, prescribing 50 to 89 daily MME, OR: 1.76, 95%CI: 1.65, 1.87; 90 to 119 daily MME, OR: 2.44, 95%CI: 1.99, 3.01; and more than 120 daily MME, OR: 1.77, 95%CI: 1.64, 1.91), and overlapping with gabapentinoids (OR: 2.26, 95%CI: 2.20, 2.32), benzodiazepines (OR: 1.32, 95%CI: 1.30, 1.35), and antipsychotics (OR: 1.21, 95%CI: 1.16, 1.26). After IPTW, chronic opioid use was associated with higher risk of all-cause mortality when compared to short-term use (Hazard Ratio (HR): 1.37, 95%CI: 1.32, 1.42). Sensitivity analyses provided similar results. CONCLUSION: These findings may help healthcare managers to identify and address patients at higher risk of long-term use and riskier prescription patterns.

Effect of perioperative intravenous ibuprofen versus acetaminophen on postoperative opioid consumption and pain after general anesthesia: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Background: Ibuprofen and acetaminophen are widely used as adjuvant analgesics for postoperative pain. This meta-analysis compared the effects of intravenous (IV) ibuprofen and acetaminophen on postoperative opioid consumption and pain intensity after general anesthesia. Methods: PubMed/MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to May 2023. Randomized controlled trials (RCTs) comparing the effects of perioperative IV ibuprofen and acetaminophen on postoperative opioid consumption and pain after general anesthesia were included in the meta-analysis and trial sequential analysis (TSA). Results: Eight studies with 494 participants were included. Compared to IV acetaminophen, IV ibuprofen significantly reduced 24 h opioid consumption, presented as morphine equivalents (mean difference [MD]: -6.01 mg, 95% CI [-8.60, -3.42], P < 0.00001, I2 = 55%), and pain scores (on a scale of 0-10) at 4-6 h (MD: -0.83, 95% CI [-1.29, -0.37], P = 0.0004, I2 = 65%) and 12 h (MD: -0.38, 95% CI [-0.68, -0.08], P = 0.01, I2 = 11%) postoperatively. These results were statistically significant in TSA. Pain scores at 24 h postoperatively and side effects were not significantly different between the two groups in the meta-analysis, and TSA revealed that the sample size was too small to adequately evaluate the effects, requiring further studies for conclusive results. Conclusions: Perioperative IV ibuprofen reduced 24 h opioid consumption and pain severity up to 12 h postoperatively compared to acetaminophen. Additional research is required to assess pain intensity beyond 12 h and side effects.

Rectal versus intravenous administration of acetaminophen; Clinical investigation of plasma level, analgesic, and antipyretic effects on 6-month to 6-year-old children in Zabol city, Iran.

OBJECTIVES: Acetaminophen is the most widely antipyretic analgesic medicine used in adults and children worldwide. Rectal acetaminophen is widely used in children who resist or cannot take oral medications. This study was designed to compare the efficacy of rectal and IV acetaminophen in children with fever and mild to moderate pain. PATIENTS AND METHODS: total 60 children aged six months to 6-years, with fever and pain, that were treated with rectal or intravenous acetaminophen were selected and assigned in two groups. The IV group received 10 mg/kg paracetamol as an IV infusion, and the rectal group received a 15 mg/kg dose immediately after admission. Pain score was calculated using the FLACC method, and the axillary temperature was recorded at baseline and then 0.5, 1, 2, 4, and 6 hours after drug administration. Blood samples were collected at baseline and then at 30 min- intervals for the first 90 minutes. RESULTS: The trend of changes in mean pain score at different time intervals was significantly different between the two groups. Body temperature decrease was more prominent in the IV group. The plasma concentration increased in both groups significantly with time. This increase was sharper in the IV group, just in the first 60 minutes after drug administration. CONCLUSIONS: Iv acetaminophen has more rapid onset of action, while rectal dosage form control fever and pain for longer duration. Considering its favorable effects with ease of administration and lower cost, rectal acetaminophen can be a reasonable option in selected patients with pain or fever.

Relationships between self-reported prescription hydrocodone, oxycodone, and tramadol use and unintentional injuries among those with spinal cord injury.

OBJECTIVE: Identify the relationships of three frequently used prescription opioids (hydrocodone, oxycodone, and tramadol) with unintentional injuries, including fall related and non-fall related injuries among adults with chronic, traumatic spinal cord injury (SCI). DESIGN: Cross-sectional cohort study. SETTING: Community setting; Southeastern United States. PARTICIPANTS: Adult participants (N = 918) with chronic traumatic SCI were identified from a specialty hospital and state population-based registry, and completed a self-report assessment. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Self-reported fall related and non-fall related unintentional injuries serious enough to receive medical care in a clinic, emergency room or hospital within the previous 12 months. RESULTS: Just over 20% of participants reported one or more unintentional injury in the past year, with an average of 2.16 among those with at least one. Overall, 9.6% reported fall related injuries. Only hydrocodone was associated with any past year unintentional injuries. Hydrocodone taken occasionally (no more than monthly) or regularly (weekly or daily) was related to 2.63 (95% CI =1.52, 4.56) or 2.03 (95% CI =1.15, 3.60) greater odds of having at least one unintentional injury in the past year, respectfully. Hydrocodone taken occasionally was also associated with past year non-fall related injuries (OR =2.20; 95% CI =1.12, 4.31). Each of the three opioids were significantly related to fall related injuries. Taking hydrocodone occasionally was associated with 2.39 greater odds of fall related injuries and occasional use was associated with 2.31 greater odds. Regular use of oxycodone was associated with 2.44 odds of a fall related injury (95% CI = 1.20, 4.98) and regular use of tramadol was associated with 2.59 greater odds of fall related injury (95% CI = 1.13, 5.90). CONCLUSIONS: Injury prevention efforts must consider the potential impact of opioid use, particularly hydrocodone. For preventing fall related injuries, each of the three opioids must be considered.

Matching study design to prescribing intention: The prevalent new-user design for studying abuse-deterrent formulations of opioids.

PURPOSE: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. METHODS: In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. RESULTS: We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. CONCLUSIONS: Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.

Occurrence of pharmaceutically active compounds in groundwater and their effects to the human health.

Groundwater contamination by pharmaceutically active compounds (PhACs) has been considered a public health concern worldwide. Alongside the potential toxicological risk of these organic substances, many countries still rely on groundwater for drinking water supply. Thus, this study identified a priority list of seven licit PhACs, comprising acetaminophen (ACT), tramadol (TRA), carbamazepine (CBZ), erythromycin (ERY), sulfamethoxazole (SMX), metformin (MET), and oxazepam (OXZ). Consumption, concentration, and human toxicity in silico results were collected from open access databases. These three indicators were analyzed separately and grouped through a general risk index. The consumption index (data from the USA and Brazil) indicated that ACT, TRA, and MET are the most consumed. Monitoring samples from the USA and Europe (n = 816) indicated that OXZ and ERY stand out as the higher occurrence index considering both regions, but the ranking for each region showed considerable differences. When assessing toxicological risk, an index ≥ 0.5 was attributed to CBZ, MET, OXZ, SMX, and TRA. The general risk indicated the need to be attentive to MET, OXZ, and TRA as they presented ≥ 0.5 index values for at least two indicators.