BackgroundBehavioral management techniques are employed for children who are fearful and uncooperative. Pharmacologic sedation and anesthesia are frequently utilized to manage pain and anxiety in pediatric dental patients.Aim To evaluate the intraoperative and postoperative pain levels during dental treatment of children sedated with 1.5 μg/kg intranasal dexmedetomidine, 0.3 mg/kg intranasal midazolam, and nitrous oxide.Materials and methodsIn this crossover study, 24 children between the ages of five and seven years were randomly assigned to receive intranasal atomized dexmedetomidine, intranasal atomized midazolam, and inhaled nitrous oxide during three different visits. At each visit, a single pulp therapy procedure was conducted after administering the respective sedative agent, and the pain levels were documented. There was a one-week interval between each visit to allow for a washout period. The data were analyzed using IBM SPSS Statistics for Windows, Version 22.0  using the Wilcoxon signed-rank test and Kruskal-Wallis H test (p < 0.05).ResultsAll three sedative agents were equally effective in controlling postoperative and intraoperative pain. Although there was no statistically significant difference among the groups, clinically, midazolam showed lower intraoperative pain levels (mean 1.78 ± 1.42).Conclusion In pediatric dental patients, intranasal midazolam at a dosage of 0.3 mg/kg and intranasal dexmedetomidine at a dosage of 1.5 μg/kg demonstrate comparable effectiveness to nitrous oxide sedation in pain management. These options serve as effective alternatives for anxious children who may not tolerate nitrous oxide sedation. Pharmacological techniques, such as sedation, are utilized to manage children's behavior during dental procedures when non-pharmacological methods prove ineffective. Conscious sedation is often favored over general anesthesia due to its lower cost and decreased risk, but its effectiveness depends on the specific medication and delivery method employed . VariousSedative agents such as midazolam, ketamine, dexmedetomidine, and sufentanil are commonly administered through the intranasal route . DexmedeThe Council of European Dentists endorses nitrous oxide-oxygen sedation, commonly referred to as "laughing gas," as the recommended standard method of sedation . It provIn order to overcome the drawbacks associated with nitrous oxide-oxygen sedation and capitalize on the benefits of intranasal dexmedetomidine and midazolam, a comparative study was carried out to evaluate the levels of pain experienced during and after dental procedures in children who were sedated with atomized intranasal dexmedetomidine (1.5 μg/kg), atomized intranasal midazolam (0.3 mg/kg), and nitrous oxide-oxygen sedation. The null hypothesis states that there is no difference in the intraoperative and postoperative pain levels during dental procedures in children who were sedated with atomized intranasal dexmedetomidine (1.5 μg/kg), atomized intranasal midazolam (0.3 mg/kg), and nitrous oxide-oxygen sedation.Study design and protocolThis clinical trial was a randomized, three-armed crossover study that commenced after obtaining ethical clearance from an institution (IHEC/SDC/PEDO-2001/21/334). To detect any discrepancies between the groups, the study required a sample size of 20 participants with 85% statistical power at a significance level of 0.05. To accommodate a potential loss to follow-up of up to 20%, an additional four children were included, resulting in a total of 24 participants. Eligible children were between the ages of five and seven years, exhibiting "negative" behavior according to the Frankl scale and having an American Society of Anesthesiologists I (ASA I) physical status, who required pulp therapy in at least three lower molars. Exclusion criteria included children with known hypersensitivity to benzodiazepines, any systemic disease, special needs, or any condition that increased the risk of airway obstruction. The children were randomly divided following a computer-generated sequence of random numbers. The allocation was done using opaque, sealed brown envelopes. The study protocol, including the treatment's associated risks and benefits, was meticulously communicated to the parents following which informed consent was obtained. Before inclusion, attempts were made to implement basic behavior modification techniques, and only children who did not respond to these techniques were included in the study. Additionally, a comprehensive evaluation of the general health of all patients was carried out by the anesthetist at the hospital prior to their enrollment. The fasting protocol, as outlined by the American Academy of Pediatric Dentistry, was diligently followed before every visit . On the ProcedureA mucosal atomization device  attached to a 1 ml syringe was used to administer either 1.5 μg/kg of dexmedetomidine  or 0.3 mg/kg of midazolam hydrochloride  intranasally to each patient. The sedation levels were monitored to assess their effectiveness. To provide analgesia, a relative analgesia machine  was utilized, delivering a mixture of 30% nitrous oxide and 70% oxygen. The flow rate was determined by initiating the administration with 100% oxygen for two to three minutes. Following the procedure, the patients received 100% oxygen for five minutes.Once the child demonstrated signs of relaxation, topical anesthesia was sprayed onto the injection site, followed by the administration of local anesthesia. Local infiltration of articaine with adrenaline 1:100,000 (Septanest) was performed near the specific tooth of interest before proceeding with pulp therapy. The child was continuously monitored by the anesthetist throughout the entire dental procedure. This treatment protocol was consistent across all arms of the trial, with a one-week washout period between visits. Since the methods of inducing dexmedetomidine and midazolam differ from those of nitrous oxide and can be easily distinguished, both the operator and evaluator were unable to be blinded  score during the administration of local anesthesia.Statistical analysisDescriptive statistics were conducted using IBM SPSS Statistics for Windows, Version 22.0 . The data normality of pain scores was assessed using the Shapiro-Wilk test, which indicated that the scores followed a skewed distribution. To compare intraoperative pain scores, the Kruskal-Wallis H test was utilized. Intragroup comparisons of subjective pain before and after treatment were made using the Wilcoxon signed-rank test. A significance level of p < 0.05 was considered statistically significant for all analyses.The present study recruited a total of 24 children, of which 14 were female and 10 were male. However, two children did not report for all arms of the study and were therefore excluded from the analysis. Table The intragroup analysis showed that there was no statistically significant difference in the preoperative and postoperative pain scores in any of the groups (p > 0.05) Table . Figure Intraoperatively, the intranasal midazolam group showed a lower mean pain score when compared to the nitrous oxide and dexmedetomidine group. However, this was found to be statistically insignificant Table .The current study is a randomized clinical trial that compares the postoperative and intraoperative pain levels during pediatric dental treatment under the influence of intranasal midazolam, intranasal dexmedetomidine, and nitrous oxide. Our findings reveal that there is no statistically significant difference among the three groups.Midazolam, when administered orally, has limitations such as its bitter taste and variable sedative effects due to insufficient drug ingestion . TherefoAll three sedative agents used in the study possess analgesic properties, which may explain the lack of significant variation in intraoperative pain scores. Additionally, consistent application of topical anesthetic prior to administering articaine may have contributed to the uniformity in intraoperative pain levels. Individual patient factors, including anxiety levels, pain threshold, and response to sedation, can also influence perceived pain during dental procedures .Intranasal midazolam acts on the central nervous system by enhancing the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This mechanism of action produces sedative, anxiolytic, and muscle relaxant effects, which collectively contribute to pain reduction . NitrousContrary to our findings, Takkar et al. observed a notable decrease in pain scores when administering an inferior alveolar nerve block with nitrous oxide-oxygen sedation . SimilarThe strength of this study lies in its design as a three-arm crossover trial, minimizing intersubject variability, and the standardized treatment protocol for each visit to reduce bias. However, limitations included longer treatment times due to the required one-week washout period between visits, potentially introducing a carryover effect. Further research is needed to explore the underlying mechanisms and patient-specific factors that contribute to the differential efficacy of intranasal midazolam, dexmedetomidine, and nitrous oxide sedation in pain management during pediatric dental treatment.In the realm of pain management for pediatric dental treatment, the use of intranasal midazolam at a dosage of 0.3 mg/kg and intranasal dexmedetomidine at a dosage of 1.5 μg/kg has demonstrated efficacy comparable to the established gold standard of nitrous oxide sedation. By employing intranasal midazolam and dexmedetomidine, dental practitioners can provide effective pain management while minimizing the potential challenges associated with nitrous oxide inhalation. These alternative methods can be especially advantageous for children who experience anxiety and are unwilling to wear the nasal mask used with nitrous oxide administration.


Opioid administration is extremely common in the inpatient setting, yet we do not know how the administration of opioids varies across different medical conditions and patient characteristics on internal medicine services. Our goal was to assess racial, ethnic, and language-based inequities in opioid prescribing practices for patients admitted to internal medicine services.  We conducted a retrospective cohort study of all adult patients admitted to internal medicine services from 2013 to 2021 and identified subcohorts of patients treated for the six most frequent primary hospital conditions  and three select conditions typically associated with pain . We conducted a negative binomial regression analysis to determine how average administered daily opioids, measured as morphine milligram equivalents (MMEs), were associated with race, ethnicity, and language, while adjusting for additional patient demographics, hospitalization characteristics, medical comorbidities, prior opioid therapy, and substance use disorders. Discussion. There are notable inequities in opioid prescribing based on patient race, ethnicity, and language status for those admitted to inpatient internal medicine services across all conditions and in the subcohorts of the six most frequent hospital conditions and three pain-associated conditions. This represents an institutional and societal opportunity for quality improvement initiatives to promote equitable pain management. The study cohort included 61,831 patient hospitalizations. In adjusted models, we found that patients with limited English proficiency received significantly fewer opioids  compared to English-speaking patients . Asian , Latinx , and multi-race/ethnicity patients  received significantly fewer opioids compared to white patients . American Indian/Alaska Native  patients received significantly more opioids. Significant inequities were also identified across race, ethnicity, and language groups when analyses were conducted within the subcohorts. Most notably, Asian and Latinx patients received significantly fewer MMEs and American Indian/Alaska Native patients received significantly more MMEs compared to white patients for the top six most frequent conditions. Most patients from minority groups also received fewer MMEs compared to white patients for three select pain conditions.  The opioid epidemic continues to grow, with a record 107,270 drug overdose deaths in 2021, up from 92,478 in 2020 . ResearcMultiple studies to date have identified notable differences in opioid prescribing practices in emergency medicine care for patients with limited English proficiency (LEP) with traumatic injuries  and in cThe objective of our study was to assess whether race, ethnicity, and language status were associated with opioid prescriptions for patients hospitalized on an internal medicine service across all medical conditions, the most frequent treated conditions, and common pain-associated conditions.We utilized electronic health record (EHR) data from the University of California San Francisco (UCSF) Helen Diller Medical Center, a 785-bed urban academic teaching hospital, to conduct a retrospective cohort study among hospitalized adults discharged from the internal medicine services from January 2013 to September 2021. All data were extracted from our local EHR, Epic, with specific data pulled from Clarity, the relational database that stores Epic data. This included patient demographic and clinical data, including time-stamped opioid medication administration. This study was approved by the UCSF Institutional Review Board with a waiver of informed consent.All admissions for patients aged 18 years or older occurring during the study period were included in the overall cohort. The data were inclusive of each unique admission and included cases of recurrent hospitalizations as the primary hospital conditions and circumstances of each admission can be unique. Both patients who received and did not receive opioids were included. Additional subcohorts included patients whose primary hospital conditions were one of the six most frequent primary hospital conditions  and three pain-associated primary hospital conditions . A patient's primary hospital condition is designated in the EHR by the discharging clinician and linked to an ICD-10 code. This approach of selecting specific, common, hospital conditions and the most common pain-associated conditions was to reduce confounding by medical condition. For the subcohort of pain-associated conditions, abdominal pain and acute back pain have been previously identified in the literature and pancreatitis was selected as a prominent pain condition by the authors . The proThe primary outcome of interest was the average amount of daily opioids administered to patients, calculated by oral morphine milliequivalents (MMEs), rounded to the nearest integer value. MMEs are used to compare equivalent dosages across different opioid medications and create a standardized metric for analyses.We had two primary predictors. The first predictor was limited English proficiency status, defined as patients with a primary language other than English who also required an interpreter. The second predictor was race/ethnicity. This was categorized at time of admission based on patients' self-assignment to one or more racial categories per the U.S. Census Bureau and National Institutes of Health reporting standards , with additional categories of “multi-race/ethnicity” and “other/unknown.” Patients were classified as ethnically Hispanic/Latinx if Hispanic was their self-reported identity, irrespective of their racial designation. Race/ethnicity categorizations reflect socially, not genetically, designated groupings and serve as a proxy for racism , 16.Additional patient demographic and hospitalization characteristics variables used in the regression analysis included patient age, gender identity, insurance coverage, history of opioid therapy prior to admission, documented history of substance use disorder, methadone or buprenorphine therapy, medical comorbidities, care in the intensive care unit during admission, comfort care/end of life status, pain service or palliative care consultation, year of study, and primary medical team. Opioid therapy prior to admission was determined from the EHR as any opioid medications on admission medication reconciliation. The EHR did not include the specific indication for opioids prescribed prior to admission, but this variable was included because of its close association with the presence of pain-related conditions and need for inpatient analgesia. Substance use was determined in the EHR as a diagnosis included in the hospital problems across all medical center encounters or billing ICD coding. This was included given the strong association substance use disorders have with concurrent pain and opioid prescriptions. Methadone/buprenorphine therapy variables were collected in our EHR based on prescription from two years preceding to six hours after discharge. Insurance status was categorized as Medicare, Medical, Private, Self-Pay, and Other. Primary team was divided between teaching resident medicine services and attending hospitalist-only services. Medical comorbidity was calculated via the Elixhauser index .Analyses were performed using Stata software version 17. Patient demographics, hospitalization characteristics, and mean daily MME were stratified by the six most frequent primary hospital conditions and top three pain-associated diagnoses, as well as for each of the individual diagnoses in the latter two groups. Next, we fit a series of negative binomial regression models to examine the association between race, ethnicity, and LEP status and mean daily MME, while adjusting for the patient demographics, hospitalization factors, opioid therapy prior to admission, substance use history, methadone or buprenorphine therapy, year of study, insurance status, and medical comorbidities. For each regression, we also tested for the interaction between race/ethnicity and LEP status. To accomplish this, we assessed goodness of fit for each model and ultimately included the interaction term in the overall model and the models for the six most frequent conditions as there was a significant improvement in model fit when the interaction term was included. There was no improvement in goodness of fit when the interaction between race/ethnicity and LEP status was included for the select pain condition models. Cluster robust variance by medical record number was applied to address readmissions for the same patients within the study period. The negative binomial regression approach was selected as there was a widely dispersed distribution of MMEs, including many patients who did not receive opioid medications during their admission , 19. ForOur study cohort included 61,831 patient hospitalizations. There were 36,237 (59%) patients who received opioid medications during their hospitalization. We included 13,062 patients in the subcohort of the top six most frequent primary hospital conditions and 1,944 patients in the subcohort of the three pain-associated primary hospital conditions . These sAcross all conditions, patients received an average of 68.8 MMEs per day. Patients from the subcohort of top six most frequent primary hospital conditions received an average of 52.7 MMEs per day, and patients from the subcohort of the three select pain-associated diagnoses received an average of 130.88 MMEs per day . There ap < 0.05 level.Each model adjusted for patient demographics, hospitalization factors, opioid therapy prior to admission, substance use history, methadone or buprenorphine therapy, year of study, insurance status, and medical comorbidities. All significance testing was performed at the White patients received an average of 103 daily MMEs (95% CI: 94–112). Asian , Latinx , and multi-racial/ethnic  patients received significantly fewer opioids compared to white patients. American Indian/Alaska Native  patients received significantly more daily average opioids compared to white patients. Patients without LEP received an average of 101 daily MMEs (95% CI: 91–111), while patients with LEP received significantly fewer daily opioids .White patients received an average of 175 daily MMEs (95% CI: 142–207). Asian  and Latinx  patients received significantly fewer opioids compared to white patients. American Indian/Alaska Native patients received significantly more opioids  compared to white patients. Non-LEP patients received an average of 155 daily MMEs (95% CI: 129–182), while patients with LEP received significantly less, an average of 114 daily MMEs (95% CI: 85–144).White patients received an average of 157 MMEs (95% CI: 138–175). Asian , black , Latinx , Native Hawaiian and Other Pacific Islander , and patients categorized as other  received significantly fewer opioids compared to white patients. Non-LEP patients received an average of 141 daily MMEs (95% CI: 129–154), while patients with LEP received significantly fewer daily opioids .Forest plots of the average marginal effects across race/ethnicity from the negative binomial regression are available in In this study, we found notable racial, ethnic, and language-based inequities in opioid prescribing for patients hospitalized on internal medicine services. Patients with LEP received significantly fewer opioids in general, when treated for the most frequent conditions and when treated for conditions typically associated with pain such as abdominal pain, acute back pain, and pancreatitis. Asian and Latinx patients received significantly fewer opioids than white patients in the overall cohort and in the subcohorts of the six most frequent primary hospital conditions and three select pain-associated conditions. Notably, black patients did not receive significantly different opioid medications than white patients in the overall cohort but received significantly fewer opioid medications in the subcohort of the select pain-associated conditions.Our findings suggest that differences in prescribing practices by race, ethnicity, and language persist even after controlling for factors such as intensive care admission, consultation with a pain or palliative care service, comorbidities, opioid use prior to admission, and methadone or buprenorphine therapy. Importantly, our regression models also incorporated interaction terms to accurately reflect the complex relationships that exist between the variables in our models. Patients with LEP often have lower quality and satisfaction of care and understanding of treatment plans and experience a higher incidence of medical errors –25. Langn = 61,831), top 6 conditions , and 3 select pain conditions  allows for a more nuanced understanding of where inequities are most prevalent in the inpatient setting. This granular approach can help to identify areas for practice change and quality improvement. For example, we found that black patients did not receive significantly different opioids across all conditions in the overall cohort, but for the top three pain-related conditions, they received substantially fewer compared to white patients. We found that patients with LEP received fewer opioids compared to non-LEP patients in the overall cohort, for the top 6 conditions and the three select pain conditions. Using pancreatitis as a case example, black patients received nearly 40% fewer opioids for a pancreatitis admission compared to white patients. Patients with LEP received an average of 30.8 MMEs/day while English-speaking patients received 136.2 MMEs/day, a more than fourfold difference. These are clinically meaningful differences. A standard tablet of 5 mg oxycodone is equivalent to 7.5 MMEs. Patients with LEP and pancreatitis in the above example, on average, would receive the equivalent of 14 fewer 5 mg tablets of oxycodone per day. Collecting these data at an institutional or departmental level enables clinicians to identify tangible targets for improvement to promote equity. Furthermore, focusing on specific diagnoses or groupings of diagnoses that have the most pronounced inequities can enable the formulation of more equitable guidelines for pain management and quality improvement measures for institutions.These findings build on our previous research demonstrating racial and ethnic inequities in discharge opioid prescribing across all conditions on internal medicine services . We haveFinally, there is an argument that fewer opioids for certain patient groups may be a positive or protective finding . While wThere are limitations to our study. First, our data were collected from a single center. While our medical center is diverse, we recognize that practice patterns differ across the nation and some institutions may have pain pathways that promote more standardized care. We do however have nine years of data, with a substantial number of patients, which drives the power behind our findings. Second, our dataset did not allow us to adjust for the reported pain scores and administration of other nonopioid pain medications like acetaminophen and NSAIDs, which can impact opioid medicine prescriptions in the inpatient setting. Third, as we identified the primary hospital conditions for the subgroups, there is a possibility of misclassification in the assignment of primary hospital condition. While our analysis adjusted for comorbidities, opioid, methadone, and buprenorphine use on admission, we are unable to determine the specific indication for each individual opioid administration from the EHR. For example, while a patient may be admitted for cellulitis, a one-time administration of hydromorphone for back pain would not be discernible from our EHR. Non-LEP patients in our cohort received more daily opioids associated with a primary hospital condition of pneumonia than patients with LEP did for abdominal pain, but it is unclear what specific diagnosis or underlying pathophysiology is driving that difference. While our approach of looking at progressively smaller subcohorts is an improvement on previous study designs, there can still be even more granular ways of assessing opioids by indication for specific conditions and even individual clinicians. Fourth, while the regression analyses adjust for comorbidities, our model inherently cannot account for the sum total of hospital problems a patient is being treated for and the complexity of pain that can result from multiple conditions. Fifth, we do not have access to interpreter use data. It would be helpful to know whether the actual use of an interpreter was associated with different medication management for patients with LEP or if there was another mechanism for this inequity.Our study demonstrates that racial, ethnic, and language-based inequities in opioid prescribing practices, previously identified in subspeciality and outpatient settings, and on discharge, are also prevalent for patients while hospitalized. To our knowledge, this is the first study to examine opioid prescriptions in the inpatient setting for medicine patients across multiple common medical- and pain-related diagnoses. This contributes to a better understanding of how opioid medications are prescribed for hospitalized patients and how prescribing practices may be optimized to effectively manage pain while minimizing overprescribing and inequitable prescriptions.Our findings offer directions for future research and quality improvement work to further understand and better address clear inequities in patient care. Within our institution, these findings represent an opportunity to explore the etiology of these inequities and the impact of implicit bias. Our next steps will include a qualitative examination of patients and providers to better understand differences and identify root causes of inequities in pain assessment and management. The identification of specific patient groups  and specific diagnoses  can serve as a starting point for the development of pain management guidelines, like postsurgical care plans in other fields. Expanding work to include analyses beyond our institution will be important to validate these findings across different practice settings and patient populations. Finally, examining the relationship between administered opioid prescriptions and documented pain assessments by nurses and clinicians, incorporating linear mixed and cross-classified multi-level modeling, and differences in scheduled vs. as needed opioids would help to better elucidate causal pathways. In this future approach, we will also explore the possibility of predictive machine learning analyses.


Background and Objectives: Pain is still undertreated among ICU patients, especially cognitively impaired patients. Nurses play a crucial role in their management. However, previous studies found that nurses had insufficient knowledge about pain assessment and management. Some nurses’ socio-demographic characteristics, such as being female; age; years of experience; type of unit, either medical or surgical; education level; years of nursing experience; qualification; position; and hospital level, were found to be associated with their practices of pain assessment and management. This study aimed to examine the association between nurses’ socio-demographic characteristics and the use of pain assessment tools for critically ill patients. Materials and Methods: A convenience sample of 200 Jordanian nurses responded to the Pain Assessment and Management for the Critically Ill questionnaire to achieve the study’s aim. Results: The type of hospital, academic qualification, years of experience as a critical care nurse, and hospital affiliation were significantly associated with increased use of self-report pain assessment tools for verbal patients, while the type of hospital and hospital affiliation was significantly associated with an increased use of observational pain assessment tools for nonverbal patients. Conclusion: Examining the association between socio-demographic characteristics and the use of pain assessment tools for critically ill patients is essential for quality pain practice. Pain is a crucial problem in critically ill patients . CriticaUncontrolled pain places patients at a higher risk for adverse psychological and physiological consequences that may be life-threatening . UntreatPain is still undertreated among ICU patients, especially cognitively impaired patients . Given tPain assessment is still a key measure among critically ill ICU patients and should be performed as early as possible. Among ICUs patients, such as those who are cognitively impaired, intubated, or with dementia or communication deficits, the pain remains unrelieved and undertreated due to the inability to self-report. Nurses still feel it is somewhat unimportant to assess pain among cognitively dis-intact patients compared to those who are cognitively intact . Self-reBased on the evidence, there is a gap in knowledge regarding the association between nurses’ socio-demographic characteristics and using pain assessment tools globally. This study will help bridge this gap to see where future services in Jordan could be developed to better suit critically ill patients’ needs. The study’s results will generate principal evidence of the necessity of assessing and managing pain and developing interventions to increase awareness and knowledge and improve practices regarding pain assessment and management among nurses. Based on our knowledge, this is the first study conducted in Jordan to assess the relationship between nurses’ socio-demographic characteristics and using pain assessment tools. The study aimed to examine the association between nurses’ socio-demographic characteristics and the use of pain assessment tools for critically ill patients in Jordan.This is a descriptive correlational study. The researchers selected three Jordanian hospitals  according to their convenience for this study to recruit a convenience sample of 200 registered nurses who are working in ICU settings with a minimum clinical experience of 6 months. The teaching hospital has a total capacity of 750 beds, with three ICUs for adults: a critical care unit (CCU), a cardiac intensive care unit (CICU), and an intermediate ICU. The public hospital has a total capacity of 400 beds, with two ICUs for adults: a critical care unit (CCU) and a cardiac intensive care unit (CICU). In contrast, the private hospital has a total capacity of 150 beds, with one ICU for adults: a cardiac intensive care unit (CICU). After calculating the required sample size based on the G*Power analysis, which used a power of 0.80 and a medium effect size of 0.25, the recruited sample was sufficient for yielding significant statistical analyses and controlling for incomplete data.The Institutional Review Board (IRB) department of Jordan University of Science and Technology approved this study. Written consent was obtained from the participants before data collection. Voluntary participation was maintained throughout the whole procedure of data collection, as well as the confidentiality and privacy of collected data. The participants were informed that they could withdraw from the study at any time. No personal information about the participants was disclosed to anyone.The use of pain assessment tools among critically ill patients was measured using the four items of the Pain Assessment and Management for the Critically Ill questionnaire developed by Rose et al. . The fouRegarding the use of pain assessment tools for nonverbal critically ill patients, the nurses were categorized into the “Yes” or “No” group according to self-report responses on the relevant item in the questionnaire: “do you use an observational pain assessment tool for patients unable to communicate?” Then the nurses selected a specific observational pain tool that they used for nonverbal patients from multiple choices.The English version of the questionnaire was used in the study since English is the primary language of nursing instruction in Jordanian hospitals. Permission to reuse the instrument was granted from the developers . The queThe demographic characteristics of participants, including gender, age, academic qualification, years of clinical experience, usual shift rotation, employment status, and ICU primary specialty, were collected by a self-administered demographic questionnaire filled out by the nurses.After obtaining the IRB approval, the researchers agreed with the administrators of the selected hospitals on the dates/times for data collection according to the potential participants’ work schedules. The researcher sent an invitation email to participate to all potential participants after getting a list of their emails and discussing their eligibility with their administrators. The researchers met with all nurses who responded to the invitation email in a private and quiet room in a group of 20 to briefly describe the study’s promise and get their written consent. The nurses who gave their consent were handed a folder containing the study questionnaire and asked to drop it at the reception counter of their work department when they finished. The average time required to fill out the questionnaire was 10 min. A week later, the researcher came back to collect the completed questionnaires. The data were collected in May 2022.SPSS version 25.0 was used to analyze the data related to the study purpose. Percentages and frequency were used to describe the proportion of nurses using the pain assessment tools for their verbal and nonverbal patients. Post hoc analysis involved pairwise comparisons, using multiple z-tests with a Bonferroni correction to examine the difference in the frequency of pain assessment tools for verbal and nonverbal patients between independent nurse proportions. Binomial logistic regression analysis was performed to determine the significant predictors of using pain assessment tools for verbal and nonverbal patients.The participating nurses in the present study had an average age of 27.24 ± 3.66 years. Most of the nurses were males, holding a bachelor’s degree, working as a registered nurse for five years and above, and working in a teaching hospital. The details of nurses’ socio-demographic characteristics are outlined in p = 0.022).The post hoc analysis involved pairwise comparisons using multiple z-tests of two proportions with a Bonferroni correction  shows stp ≤ 0.001) higher than that of nurses with a diploma or master’s degree. In terms of the years of experience as a critical care nurse, the proportion of nurses who had a clinical experience of five years or less and used the pain assessment tool in patients who are able to report was statistically significantly higher than that of nurses with experience for 5–10 years or more than 10 years (p ≤ 0.001). Regarding hospital affiliation, the proportion of nurses affiliated with a teaching hospital and used the pain assessment tool in patients who are able to report was statistically significantly lower than that of nurses affiliated with a large community or moderate community hospital (p = 0.013). Other variables, including employment status, usual shift rotation, number of ICU, number of beds in the ICU, and years of experience as a registered nurse, were not significantly associated with using pain assessment tools for patients who are able to report (p ≥ 0.05).Regarding academic qualification, the proportion of nurses with a bachelor’s degree who used the pain assessment tool in patients who are able to report was statistically significantly (p < 0.001). Regarding hospital affiliation, the proportion of nurses who worked at a teaching hospital and used the pain assessment tool in patients who are unable to report was statistically significantly lower than that of nurses with a large community of ≥200 beds or a moderate community of 50–199 beds (p < 0.001).The proportion of nurses using pain assessment tools for patients who are unable to self-report symptoms was significantly different according to the type of hospital and hospital affiliations . The proOther variables, including qualification, employment status, usual shift rotation, number of ICU, number of beds in the ICU, years of experience as a registered nurse, and years of experience as a critical care nurse, were not significantly associated with the use of the pain assessment tool for patients who are unable to report.2(8) = 29.53, p < 0.0005. The model explained 29.4% (Nagelkerke R2) of the variance in using pain assessment tools and correctly classified 90.5% of cases. Of the four predictor variables, the experience as a critical care nurse was a statistically significant predictor  = 28.872, p < 0.0005. The model explained 30.5% (Nagelkerke R2) of the variance in using pain assessment tools and correctly classified 87.45% of cases. Only one of the two predictor variables was statistically significant (A binomial logistic regression was also performed to ascertain the effects of qualifications, years of experience as a critical care nurse, type of hospital, and hospital affiliation on the likelihood that participants used pain assessment tools for patients who are unable to self-report. The logistic regression model was statistically significant, χnificant . Nurses Our study found that various nurses’ socio-demographic characteristics influenced their practice toward pain among critically ill patients. Consistently, previous studies found significant differences between nurses working in private, public, and university-affiliated hospitals regarding the level of knowledge and practice, academic and clinical qualifications, job satisfaction, and patient-to-nurse ratio, which may affect pain quality of care ,22. MoreConversely, recent studies ,25 showeSeveral studies revealed that higher nurses’ experience levels facilitated adequate pain evaluation and treatment among critical care patients ,30,31,32In the current study, the proportions of nurses using pain assessment tools for verbal and nonverbal critically ill patients seem to be equal. However, nurses using observational tools for assessing pain behaviors in nonverbal patients may misunderstand or misinterpret these behaviors . The behThe study findings could be utilized to develop continuing education programs for nurses on the use of pain assessment tools for critically ill patients. Moreover, nursing scholars may benefit from the findings to create course syllabi related to pain assessment practice for critically ill patients. Moreover, the findings could contribute to changing pain practice policies in Jordanian hospitals to be tailored to the special comfort needs and challenges of critically ill patients, especially those who are unable to self-report symptoms. Further examinations of the issue of underassessment of pain in critically ill patients and how it relates to unrelieved pain among those patient groups are recommended.The current study has some limitations. The current study employed a descriptive correlational design, which fails to establish a causal relationship among the studied variables. The current study’s findings cannot be generalized to all nurses from all clinical departments since the recruited nurses are working in ICUs. Using a convenience sampling method to recruit the nurses in this study may be associated with a selection bias and threaten the internal validity of the study’s findings. Furthermore, using a self-reported questionnaire may be associated with recall bias and measurement errors. The study measured the nurses’ self-reported responses on using a pain assessment tools questionnaire, not the accuracy of using pain scales or the action taken if pain scores were high. Furthermore, the unequal sample sizes in the comparison groups may impact the results of some comparisons. The results of the t-test need to be interpreted within the context of the unequal comparison group sizes, and this may induce bias and limit the generalizability of the results. Future studies should consider a larger sample size and well-controlled research designs and statistical models. Moreover, this study evaluated the use of specific pain scales and not potential other strategies for pain assessment. More controlled and multidisciplinary research, using experimental designs, larger samples, and multisite settings, is needed to overcome the abovementioned limitations.The present study examined the association between nurses’ socio-demographic characteristics and their use of pain assessment tools for verbal and nonverbal critically ill patients. The type of hospital, academic qualification, years of experience as a critical care nurse, and hospital affiliation were significantly associated with an increased use of self-report pain assessment tools for patients who are able to self-report. In contrast, hospital affiliation was significantly associated with an increased use of observational pain assessment tools for patients who are unable to self-report. The nurses’ related factors, such as their demographic and professional characteristics and how they relate to the problem of delayed management of pain among critically ill patients, especially those unable to self-report symptoms, need future examinations to reach optimal pain management.


IntroductionOrthognathic surgical procedures include a series of surgical operations in which interventions are applied to the maxilla, mandible, or both for occlusal or aesthetic concerns due to facial skeletal development deformities. Double-jaw surgeries have the highest pain scores, in which both maxilla and mandible bones are intervened. This study aimed to compare the efficacy of individual applications of paracetamol and tenoxicam with their combined application on postoperative pain and opioid consumption in patients undergoing double-jaw surgery.MethodsIn this randomized, double-blind study, 60 patients undergoing double-jaw surgery were allocated into three groups, with each having 20 patients: the paracetamol group, the tenoxicam group, and the paracetamol-tenoxicam combination group. Pain intensity was evaluated using the visual analogue scale (VAS) at intervals of 30 minutes, 60 minutes, 120 minutes, and again at the 24th postoperative hour. Additionally, the consumption of opioids and other rescue analgesics was documented over the 24-hour postoperative period.ResultsThe VAS values at 30 minutes, 60 minutes, and 24 hours were lower in the paracetamol-tenoxicam group compared to the other groups (p<0.001). The need for a rescue analgesic drug in the first 24 hours was not observed in the tenoxicam and paracetamol-tenoxicam groups.ConclusionIt was concluded that both tenoxicam and paracetamol-tenoxicam combinations, especially the tenoxicam-paracetamol combination, were good options for postoperative analgesia in patients with double-jaw surgery. Postoperative pain generally occurs due to inflammation and edema related to tissue trauma. Many factors, such as cautery-related burns, surgical incisions, dissections, and instrumental procedures such as cutting, stretching, or compression, cause surgical tissue trauma. The transmission pathways of pain begin with specific receptors that release local mediators in the periphery. Subsequently, the pain signals are transmitted to central nervous system structures, particularly the thalamus and cerebral cortex, where they are processed and ultimately perceived as pain. This process, which starts with the reception and transmission of the pain sensation from the periphery and ends with the perception in the upper centers of the nervous system, is quite complex and is called nociception . The natOrthognathic surgical procedures include a series of surgical operations in which interventions are applied to the maxilla, mandible, or both for occlusal or aesthetic concerns due to facial skeletal development deformities. Double-jaw surgeries have the highest pain scores in which both maxilla and mandible bones are intervened . CompareThus, our hypothesis was that the combined use of paracetamol and tenoxicam could effectively manage postoperative pain, potentially reducing the need for postoperative opioid analgesics. Considering this, the primary aim of this study was to compare the effects of tenoxicam, paracetamol, and tenoxicam-paracetamol combination analgesic applications on the postoperative visual analogue scale (VAS) score of double-jaw surgery patients. In line with this aim, the primary outcome targeted was the postoperative VAS scores. The secondary aim was to investigate the effects of these interventions on the number of both opioid and rescue analgesic drug consumption postoperatively. Correspondingly, the secondary outcomes encompassed the postoperative consumption of both opioid and rescue analgesics.ClinicalTrials.gov (NCT05508451).The study was conducted by the Declaration of Helsinki and was carried out with the approval of the Ethics Committee of Erciyes University Faculty of Medicine (2018/303). Written informed consent was taken from all the patients participating in the study. Sixty patients between 18 and 50 years of age, both genders, who were scheduled for double-jaw surgery under general anesthesia and classified as American Society of Anesthesiologists (ASA) risk class I or II were included in the study. Exclusion criteria for the study patients were as follows: having liver or renal dysfunction and known coagulopathy disorder, having psychiatric or medical conditions that might impair communication or compliance with the study procedures, having allergy or contra-indications to the study drugs, and pregnancy. In addition, patients who were planned to undergo additional simultaneous surgical procedures such as genioplasty were not included in the study. The same surgery team performed all surgeries. This study was retrospectively registered on Study design, detailed methodology, and follow-upThis is a single-centered, randomized, double-blind study conducted between May 2019 and April 2021. Randomization was carried out using the coin-toss method. Prior to the study, the nurse was briefed about the study design, and she was responsible for the randomization process and setting up the groups, ensuring an unbiased allocation of participants into the three study groups. Treatments consisted of IV infusions of paracetamol 1 g, tenoxicam 20 mg, and a combination of paracetamol and tenoxicam. The nurse, who was privy to the contents of the solutions, including the drugs they contained, recorded this information. Other clinical personnel were not informed about the specific group allocations to maintain the integrity of the study. These solutions were then administered to the patients. The specific drugs contained in each solution were only revealed after the study was completed, at which point the groups were formed accordingly.Standard monitoring, including pulse oximetry, electrocardiography, and non-invasive blood pressure assessment, was performed for all patients. Anesthesia induction was achieved using fentanyl (1 microgram/kg), propofol (2 mg/kg), and rocuronium (0.5 mg/kg). Additionally, 2% sevoflurane was used for maintenance.2 were recorded at 5-minute intervals during the application of these solutions. Furthermore, an evaluation of patients' pain severity was conducted upon emergence from anesthesia, following extubation in the operating room. This was assessed using a 5-point verbal scale, with the points defined as follows: (0) none, (1) a little, (2) moderate, (3) a lot, and (4) complete. A modified Aldrete Scoring System was used in the postoperative period to assess recovery. The time to reach the modified Aldrete recovery score of 9 during recovery from anesthesia was noted for each patient.Approximately 30 minutes before the conclusion of the operation, as the mucosal closure began, intravenous solutions containing the designated analgesic drugs  were administered to the patients. These analgesics were infused continuously until the final suture was placed. These solutions were prepared by a nurse to ensure the appropriate concentration and volume for each patient. Vital signs such as heart rate, mean arterial blood pressure, and SpOPain intensity was assessed on a 100-mm VAS, where 0 = no pain and 100 = worst possible pain at 30 minutes and at the first, second, and 24th hour after surgery. The decision to include the 30th-minute evaluation was made based on our study's design and the timing of the drug administration, ensuring an accurate assessment of the initial analgesic effects. In our study, as the primary postoperative analgesic, an opioid analgesic drug, specifically 50 mg IV tramadol, was administered to the patients whenever their VAS scores reached or exceeded 40. This was to ensure immediate pain relief. However, if a patient explicitly requested additional pain relief or if the primary analgesic was not sufficient, we provided rescue analgesia. In such cases, IV paracetamol was chosen as the rescue analgesic and was administered only after a thorough pain assessment to ensure the patient's safety and comfort. The number of both opioid and rescue analgesic drugs administered based on VAS scores was recorded. Postoperative analgesic consumption was specifically monitored and recorded for the initial 24 hours following the surgery to assess the immediate pain management efficacy of the treatments. The amount of maxillo-mandibular movement for each patient was also recorded. Postoperative complications such as nausea, vomiting, arrhythmia, agitation, and surgical duration were the recorded other parameters for the study. The consort flow diagram of the current randomized study is given in Figure Statistical analysesData analysis was performed using the Statistical Package for the Social Sciences (SPSS) software Version 26 . Descriptive statistics were given several units (n), percent (%), mean ± standard deviation, median (M), minimum (min), maximum (max), and interquartile range (IQR). The normal distribution of the data of numerical variables was evaluated using the Shapiro-Wilk normality test. Pearson’s chi-square and Fisher’s exact tests were used to compare groups with categorical variables. If the results of the chi-square analysis were significant, subgroup analyses were performed using a Bonferroni-corrected two-ratio z-test. Comparison of the normally distributed variables between the groups was done using a one-way analysis of variance. Variables that did not show normal distribution were compared using the Kruskal-Wallis analysis. If the Kruskal-Wallis analysis result was significant, the Dunn-Bonferroni test was used as a multiple comparison test. A two-way analysis of variance was used in repeated measurements from general linear models to compare the groups' heart rate and blood pressure values according to the measurement times. In the study, Spearman's rho correlation coefficient was used to examine the relationship between the covariates and the study's primary outcomes, which were the VAS scores and the number of postoperative opioid consumptions. A p-value of <0.05 was considered statistically significant in all comparisons.A post hoc power analysis was conducted in accordance with the effect sizes proposed by Cohen, using G*Power . With 95Age, gender, BMI, and ASA distributions were statistically similar between the groups . Specifically, the paracetamol-tenoxicam combination group demonstrated a shorter recovery time, with a median of 5.0 minutes range: 3.0-10.0), compared to both the paracetamol group  and the tenoxicam group  guidelines . ERAS waThere are studies in which NSAIDs are included in the analgesia protocol in double-jaw surgery. As a result of these studies, it was reported that postoperative pain and opioid use were reduced in patients using NSAIDs ,19. In aParacetamol and NSAIDs have different mechanisms of action. A systematic review of randomized trials found that the combination of paracetamol with NSAIDs was more effective for postoperative pain after various surgical procedures than paracetamol or NSAIDs alone in 85% and 64% of studies, respectively . In the The application of an arch-bar and the presence of edema in the soft tissue, which is the area that also includes the respiratory tract, necessitate not performing additional applications, such as opioid applications that will trigger postoperative respiratory depression in double-jaw surgeries. For this reason, we believe that there is a need for an analgesic method to minimize and even reset the need for opioid use, which may cause sedation and respiratory depression in the postoperative period, especially in double-jaw surgeries.Tenoxicam belongs to the oxicam subgroup of the nonspecific cyclo-oxygenase (COX) inhibitor family. Analgesic and anti-inflammatory activity mainly occurs through the inhibition of prostaglandins in the COX-2 enzyme pathway. Prostaglandins in the COX-1 enzyme pathway are protective prostaglandins for the gastrointestinal and cardiovascular systems. Tenoxicam is 1.34 times more effective in inhibiting COX-2 compared to COX-1 . This meLimitationsOne limitation of our study is the absence of VAS scores collection between 120 minutes and 24 hours. However, this decision was based on specific rationales. The pharmacokinetics and dynamics of the analgesic drugs used in our study typically exhibit their peak effects within the initial hours post-administration. Therefore, by assessing the VAS scores at 30 minutes, first hour, and second hour, we aimed to capture the immediate postoperative analgesic effects provided by the drugs. This approach helped us understand the effectiveness of our pain management strategies in the early postoperative period. Another limitation of this study was that the time of the first analgesic drug administration needed to be recorded. However, according to the results of our research, it was observed that no additional analgesic drug was used according to the VAS scores evaluated up to the postoperative 2 hours of the paracetamol-tenoxicam group.In conclusion, the current study revealed that both tenoxicam and the combination of tenoxicam and paracetamol effectively reduce postoperative pain intensity and decrease opioid consumption in patients undergoing double-jaw surgery. However, the paracetamol-tenoxicam combination exhibited certain advantages over tenoxicam alone. Notably, the combined group had a higher proportion of patients experiencing no pain upon emergence from anesthesia, boasted shorter recovery times, and recorded lower VAS scores at 30 minutes, 60 minutes, and 24 hours postoperatively. These outcomes underscore the potential superiority of combining tenoxicam and paracetamol for postoperative analgesia in this patient group.


Mathematical integration of all complications from the Clavien–Dindo classification into one number called the comprehensive complication index provides a novel method to capture morbidity. This objective of this study was to compare the evaluations of complications between the novel comprehensive complication index and Clavien–Dindo classification for portal hypertension patients who underwent splenectomy plus pericardial devascularization.Patients treated with either splenectomy plus simplified pericardial devascularization or splenectomy plus traditional pericardial devascularization were included retrospectively. Correlation and logistic regression analyses of the postoperative hospital stay and total hospitalization expense were compared between the comprehensive complication index and Clavien–Dindo classification. The cumulative sum-comprehensive complication index was generated and compared between operation types.R2 values for the comprehensive complication index and Clavien–Dindo classification were 0.15 and 0.14, respectively. The cumulative sum-comprehensive complication index graph showed a steady dynamic decrease in the cumulative sum score for the individual operation type, with splenectomy plus simplified pericardial devascularization revealing a more notable decrease than splenectomy plus traditional pericardial devascularization.The Child–Pugh classification at admission, spleen thickness, and intraoperative blood loss were risk factors for high comprehensive complication index. Comprehensive complication index showed a stronger relationship with the postoperative hospital stay and total hospitalization expense than the Clavien–Dindo classification. Logistic regression analysis of the postoperative hospital stay demonstrated that the Comprehensive complication index is an excellent method to assess postoperative morbidity in portal hypertension patients. The cumulative sum-comprehensive complication index chart can better dynamically monitor and compare different operation types. Splenectomy plus simplified pericardial devascularization is better than splenectomy plus traditional pericardial devascularization at decreasing cumulative sum-comprehensive complication index. The risk factors for a high comprehensive complication index (CCI) score were the Child–Pugh classification at admission, spleen thickness, and intraoperative blood loss.The CCI had a stronger correlation with the postoperative hospital stay and total hospitalization expense than the Clavien–Dindo classification (CDC).Postoperative hospital stay was greater than that of the CDC. All operation types showed a dynamic decrease in the cumulative sum (CUSUM) score in the CUSUM–CCI model, although the decrease obtained with simplified splenectomy plus pericardial devascularization (SPD) was more notable than that obtained with traditional SPD.1 Splenectomy plus pericardial devascularization (SPD) is the main operative method for the prevention and treatment of portal hypertension. Although great progress has been made in surgical techniques and methods in recent years, the incidence of perioperative complications is still extremely high. Therefore, control and monitoring of complications are necessary.3 Unfortunately, few studies have comprehensively evaluated the postoperative complications of PH patients undergoing SPD.Portal hypertension (PH) is a major complication of cirrhosis that manifests as ascites, splenomegaly, hypersplenism, and esophageal varices. The incidence and mortality of severe esophagogastric variceal hemorrhage are extremely high and seriously threaten the life and health of patients.7 However, the CDC reports only the most severe complications and excludes other collateral complications, although typically severe complications are accompanied by various minor complications. Therefore, the CDC cannot reflect the comprehensive effect of the total complications on patients. In addition, the CDC is an ordinal and not a continuous scale; thus, the differences between 2 adjacent grades are not necessarily equal, which limits its application as an outcome variable in statistics.4To rank a complication in an objective and reproducible manner, the Clavien–Dindo classification (CDC) is conducted based on the therapy used to correct a specific complication and has been widely applied to classify complications in many fields of surgery.10 The CCI is a novel method that mathematically integrates all complications graded by the conventional CDC into one number regardless of the number and severity of the complications to capture the overall burden of an operation. Another prominent aspect of the CCI is that it is a continuous linear scale ranging from 0 (no complications) to 100 (death), can easily quantify complications and can be included in multifactor analyses. Thus, the CCI is the most attractive method for evaluation of postoperative complications. The CCI has been applied in abdominal surgery and in the context of randomized controlled trials for patients undergoing esophagectomy and has achieved better results.11 The cumulative sum (CUSUM) control technique uses a graphical tool to detect data trends and monitor surgical performances. Because the CCI represents the overall magnitude of all complications, continuous detection of the CCI can mirror the surgical performance.12Recently, the comprehensive complication index (CCI) was developed and validated in a large cohort of patients who underwent abdominal surgery. This index has higher sensitivity than the traditional evaluation method for postoperative complications.The aim of this retrospective study was to compare the evaluations of complications between the novel CCI and the conventional CDC in a large cohort of SPD patients and to identify risk factors for a high postoperative CCI score (CCI at 1 month ≥26.2). Then, we applied the CUSUM-CCI chart to monitor and compare complications between different operation types.2 The inclusion criteria were as follows: (i) PH patients with a history of upper gastrointestinal bleeding; (ii) PH patients diagnosed with esophagogastric varices and hypersplenism through clinical symptoms combined with laboratory, digestive endoscopy, or image examinations; (iii) PH patients classified as grade A or B in the Child–Pugh grading criteria or who were reduced to Child–Pugh A or B after liver preservation therapy to attain surgical indications; and (iv) patients who could tolerate general anesthesia and had no surgical contraindications. The exclusion criteria were as follows: (i) patients with acute heart failure, shock, or other vital organ diseases; (ii) patients in the acute hemorrhagic period with unstable vital signs; and (iii) patients with poor heart, lung, liver, or kidney functions. The patient characteristics, laboratory information, and perioperative characteristics were recorded from the electronic medical records. The study was reviewed and approved by the Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University (no.: 2018028). All procedures were conducted in accordance with the Declaration of Helsinki of the World Medical Association. The need to obtain written informed consent from the patients was waived due to the retrospective and anonymous nature of this study. All data were used only for statistical analysis in this study.The electronic medical record database of the Department of General Surgery at the Second Affiliated Hospital of Xi’an Jiaotong University was reviewed, and the PH patients who underwent SPD from August 2009 to March 2017 were included in this study. Two SPD types were used in our department: splenectomy plus simplified pericardial devascularization (SSPD) and splenectomy plus traditional pericardial devascularization (STPD). The surgical details were described in our previous publications.4 The CCI was the severity-weighted sum of all postoperative complications (available at http://www.assessurgery.com). The CDC grade was ascertained by the most serious complications for each patient. The range of the CCI is from 0 (no complications) to 100 (death). A CCI score greater than 26.2 (CCI ≥26.2) was considered a high CCI score based on prior studies.8Complications that occurred within 30 days after the operation were considered surgical complications, and the severity of all complications was graded using the CDC.13 In this study, the CCI of the individual operation type from 2011 to 2017 was tested in the CUSUM chart using the average CCI from August 2009 to December 2010 as the target value. To compare surgical outcomes between the 2 operation types, the combined CUSUM chart from 2011 to 2017 was presented using the average overall CCI from August 2009 to December 2010 as the target value. Finally, overall monitoring of surgical outcomes in our department from 2011 to 2017 was depicted with a target value of the average overall CCI from August 2009 to December 2010.Details of the CUSUM control technique were provided in previous publications.P < .1 were included in the multivariate analysis. The Statistical Package for the Social Sciences version 21.0  was used for all analyses. All P values are 2 sided, and P < .05 are considered significant.Continuous variables are presented as the mean ± SD. Categorical variables are expressed as frequencies and percentages. Spearman’s correlation analysis was performed to test and compare the CCI and CDC grading systems. The correlation coefficient score of the CCI for a postoperative hospital stay (PHS) was compared to the CDC score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for a high CCI score and a longer PHS. From the univariate analysis, factors with 2), and the mean model for end-stage liver disease (MELD) score at admission was 5.96 ± 0.40.A total of 659 patients were included. The baseline characteristics are displayed in The laboratory Data and the intraoperative and postoperative characteristics of the cases are shown in ρ = 0.99).As shown in P values were all lower than .1 (<.10) for the Child–Pugh grade at admission, esophageal varices grade, variceal bleeding, hemoglobin, total bilirubin, direct bilirubin, albumin, serum creatinine, albumin–bilirubin grade, operative time, intraoperative blood loss, and spleen thickness. Then, we introduced these variables into the multivariate analysis and found that the Child–Pugh grade at admission, intraoperative blood loss and spleen thickness were independent risk factors for a high CCI score.As shown in ρ = 0.2 vs. ρ = 0.15) and THE than the CDC (ρ = 0.23 vs. ρ = 0.19). The univariate and multivariate logistic regression analyses showed that the CCI and CDC were influenced by the PHS but not the THE. In the multivariate logistic regression model for the PHS, the R2 was 0.15 when we deleted the CDC and 0.14 when we deleted the CCI ,17 liver transplantation (median 37.1),18 and cytoreduction and hyperthermic intraperitoneal chemotherapy (25.3 ± 24.1)19 have been reported. According to these previous reports and our current report regarding the use of the CCI for SPD (19.22 ± 11.92), the CCI appears to be a good method to evaluate postoperative complications. To the best of our knowledge, this study is the first to report the postoperative complications of PH patients undergoing SPD using the CCI system. The CCI score ranges from 0 (no complications) to 100 (death).20 Patients with a CCI score ≥26.2 are considered to have a severe postoperative condition.21 Here, we found that >15.63% of cirrhotic patients had a postoperative CCI score >26.2. Ascites occurred in 9.56% and pneumonia in 6.37% of the patients. Portal vein thrombosis and surgical site infections occurred in 18 (2.73%) and 11 (1.67%) patients, respectively. Two patients suffered hepatic encephalopathy. Four (0.61%) patients underwent reoperation due to intra-abdominal bleeding. Four in-hospital deaths were observed in this cohort due to severe postoperative complications or organ failure. Thus, severe postoperative conditions are common in PH patients undergoing SPD.At present, reports of complications based on the CCI system are limited. In recent prospective studies, CCI values for esophagectomy of 25.74 (8.66–43.01),22 In this study, we found that a high Child–Pugh grade at admission was associated with a high CCI score after SPD. The Child–Pugh classification is a commonly used grading standard for liver reserve function, liver parenchymal damage, and prognostic predictions in cirrhotic patients. Patients with high Child–Pugh grades are more likely to experience postoperative liver dysfunction, which potentially increases the surgical risk.23 This study is the first to show the association of this measure with a high CCI score after SPD in PH patients. Spleen thickness was another risk factor for a high CCI score. Spleen thickness was associated with the severity of cirrhosis.24 Patients with thicker spleens are more likely to experience postoperative liver dysfunction and coagulation abnormalities due to the cirrhosis severity, resulting in more complications and a high CCI. Thus, other treatment options should be considered for PH patients with high Child–Pugh classifications and thicker spleens. Intraoperative blood loss was another risk factor for a high CCI score. Intraoperative blood loss is a potential complication of surgery. Studies have shown that the risk of serious morbidity and mortality from surgery increases with the increase in intraoperative blood loss.25 Severe intraoperative blood loss can lead to postoperative anemia and even shock, especially in PH patients with poor liver function. Therefore, intraoperative blood loss should be reduced as much as possible to reduce complications.Identification of the risk factors for a high CCI score is critical for the prediction and prevention of severe complications.11 In this study, the correlation analysis showed that both the CCI and CDC had positive correlations with the PHS and THE, although the CCI exhibited a stronger positive relationship with both the PHS and THE than the CDC. The univariate and multivariate logistic regression analyses showed that the CCI and CDC were both influenced by the PHS but not by the THE, which might have been due to the different types of medical insurance used by individual patients. The R2 of the multivariate analysis was 0.15 when we deleted the CDC and 0.14 when we deleted the CCI, suggesting that the CCI had a greater share of the influence on the PHS than the CDC.26A PHS and THE are considered surrogate markers that reflect the clinical outcome.2 The CUSUM chart for the overall CCI revealed a dynamic decrease in the time sequence, indicating that the total postoperative complications were decreasing.Because the CCI system is a continuous variable, it can be mathematically integrated to form the CUSUM-CCI control chart to monitor and compare the CCIs of different operation types and to monitor overall surgical outcomes. This method can continuously update complication data and be used to instantly observe the postoperative effect and finally to provide feedback for different surgical types to reassess operation procedures. In this study, the CUSUM score showed improvement in the CCI for both SSPD and STPD. In the comparison model, SSPD exhibited a more notable decrease in the CUSUM score than STPD, indicating that SSPD was superior to STPD in terms of the CCI score and was safe, effective, simple, and easy to perform.27 Second, our study was performed in a single hospital. Thus, potential information on readmission to other hospitals was not included. Third, because the follow-up time in our study was only 1 month, we could not report the longer-term postoperative outcomes of PH patients. Despite the above limitations, we believe that our study contributes to complication evaluation and monitoring of SPD for PH patients.Nevertheless, our study still has some limitations. First, this study was a retrospective study, and thus we cannot exclude potential selection bias and residual confounding due to unknown covariates that may have affected our results.In conclusion, the CCI is an effective tool to assess the overall burden of postoperative complications for PH patients undergoing SPD. The Child–Pugh classification at admission, spleen thickness, and intraoperative blood loss were associated with a high CCI score after SPD. Thus, an elevated Child–Pugh grade at admission and a thick spleen indicate that other treatment options should be considered for PH. Surgeons should make every effort to optimize surgical decision-making and minimize intraoperative blood loss. This study also found that the CCI exhibited a stronger correlation with complications and better predicted the PHS and THE than the conventional CDC. In addition, the CUSUM-CCI control model can be used to continuously monitor and compare the surgical quality among different operation types. Further, large-scale prospective studies are needed to confirm our findings.


Opioid-induced constipation (OIC), a common side effect of opioid treatment for chronic pain, affects patient health-related quality of life (HRQL) and may prompt some patients to lower the dose or alter adherence to their opioid medication, compromising pain relief. Although health care providers (HCPs) are aware of the potential for OIC, patients may not inform their HCPs of their OIC symptoms, and HCPs may not initiate conversation regarding OIC if their patients’ pain is controlled. Patients often try to address OIC symptoms on their own by using natural approaches or over-the-counter options. When OIC is discussed in an office visit, HCPs typically recommend conventional laxatives to relieve symptoms, but the efficacy of this approach is unproven and often suboptimal. In many areas of medicine, HCP perceptions of the impact of adverse effects of treatment on a patient’s HRQL do not align with the patient’s experience.To (a) describe HCP-reported understanding of his or her patients’ experiences with OIC and (b) evaluate the level of agreement or discordance in perception between patients and their HCPs of OIC’s impact on clinical outcomes.This was a prospective, longitudinal, observational cohort study conducted in the United States, Canada, Germany, and the United Kingdom (NCT01928953) in patients aged 18 to 85 years who had been receiving daily opioid therapy for ≥ 4 weeks for chronic noncancer pain with presence of OIC in the past 2 weeks. Data were collected from retrospective chart reviews, HCP questionnaires, and web-based patient surveys. Eligible patients enrolled online and completed the Patient Assessment of Constipation-Symptoms, the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem, the EuroQOL 5 Dimensions, and the Global Assessment of Treatment Benefit, Satisfaction, and Willingness to Continue standardized questionnaires. The patient-reported component included 1 baseline survey and 8 follow-up surveys over 24 weeks. HCPs completed a web-based survey at baseline and at week 24 to assess their perceptions of OIC burden, treatment patterns, laxative use, and overall treatment satisfaction. The correspondence of patient- and HCP-reported data was evaluated for all similar outcomes from these 2 databases.Patients (N = 489) reported a mean (SD) number of bowel movements (BMs) per week and spontaneous BMs per week of 3.7 (2.9) and 1.4 (2.3), respectively, at baseline. Most (87%) reported chronic pain of ≥ 2 years duration; 65% had used opioids for ≥ 2 years; and the mean pain score at baseline was 6.3, consistent with a moderate-to-severe pain population. Most (97%) patients at baseline reported any gastrointestinal-related symptom of at least moderate intensity, with 82% reporting the same intensity of any symptom at week 24. Of the 405 patients who had seen their HCPs in the past month, 63% reported that they had spoken to their HCPs about constipation, and 62% reported that their HCPs had asked them if they had constipation in the past month. The proportion of agreement between HCPs and their patients on the presence of constipation at baseline was 61%. Similar average pain ratings between HCPs and patients (5.9 vs. 6.0) at week 24 suggested clear communication regarding the level of pain experienced by the patient; however, OIC symptoms, laxative use and effectiveness, and impact of OIC on pain management and HRQL were not fully appreciated by HCPs.The importance and severity of OIC are perceived differently by patients and their HCPs, a discordance that complicates pain management and demonstrates a need for greater communication. These disparate perceptions indicate a need for clinical education and coordination of care by HCPs to improve understanding and proactively manage OIC in patients with chronic noncancer pain. What is already known about this subjectIn the United States, patient surveys and medical record reviews suggest that 17%-67% of patients experience opioid-induced constipation (OIC) as an adverse event of their opioid pain medication.In the majority of these patients, the symptoms of OIC affect activities of daily living and health-related quality of life (HRQL) and prompt patients to decrease the dose or temporarily stop using their opioid medication to relieve their constipation.Discordance between the perceptions of health care providers (HCPs) and patients is found in many areas of medicine and may compromise patient care and disease management.What this study addsThis study investigated the perceptions of patients and HCPs about the burden of OIC with regard to symptoms, adequacy of pain management, use and effectiveness of laxative therapy, and activities of daily living in patients receiving opioids for chronic noncancer pain with the presence of OIC.Similar average pain ratings between HCPs and patients (5.9 vs. 6.0) at week 24 suggested clear communication regarding the level of pain experienced by the patient.However, OIC symptoms, laxative use and effectiveness, and the negative effects of OIC on pain management and HRQL were not fully appreciated by HCPs.3 Discordance between the perceptions of HCPs and patients is found in many areas of medicine and may compromise patient care and disease management. For example, in surveys carried out to determine the impact of gastroesophageal reflux disease (GERD) on health-related quality of life (HRQL), a disconnect was noted between patients and HCPs regarding treatment of GERD, with HCPs underestimating the use of over-the-counter therapies by their patients with GERD.4 Similarly, results obtained on HRQL questionnaires completed by HCPs and their patients with melanoma who were receiving adjuvant PEGylated interferon-α2b therapy showed that HCPs significantly underestimated the HRQL impairments that their patients were experiencing.5Effective communication between patients and their health care providers (HCPs) is recognized as essential for optimal patient outcomes, but it is often difficult to achieve in today’s time-constrained health care environment.6 Data from U.S. patient surveys and medical record reviews suggest that 17%-67% of patients experience constipation as an adverse effect of their opioid pain medication.9 The absence of general agreement on the magnitude of the problem is an indication that patients may have different perceptions of when opioid-induced constipation (OIC) becomes an issue for them. This lack of agreement further underscores the importance of better understanding patient-physician communication. Patients with OIC may experience abdominal discomfort, nausea, gas, decreased appetite, reflux, bloating, straining, incomplete evacuation, and hard bowel movements (BMs).11 In the majority (≥ 80%) of patients, these symptoms affect activities of daily living and HRQL,12 with individuals receiving opioids who developed OIC reporting significantly worse HRQL than those who did not develop OIC.13Opioids are commonly used to treat chronic noncancer pain.11 Laxatives are often used to treat OIC, but they have limited efficacy.15 Laxatives exist in a variety of formulations, including surfactants that soften the stool, osmotic agents that retain water in the gastrointestinal (GI) tract, and stimulants that promote motor activity and the secretion of fluids in the GI tract.16 Bulk-forming laxatives may not be effective for the treatment of OIC because the receptors stimulated by the increased bulk are blocked by opioids.15 Safety and low cost render over-the-counter laxatives and natural remedies appropriate first choices for pharmacotherapy; however, they have no ability to block opioid actions at GI opioid receptors.15Nonpharmacologic interventions, such as increasing fluid and dietary intake of fiber, are common first-line approaches for treating OIC but are rarely sufficient to manage the condition.14 In the international, Internet-based Patient Reports of Opioid-Related Bothersome Effects (PROBE 1) survey, 33% of patients reported that they had skipped, decreased, or ceased use of opioids to facilitate having a BM.12 Thus, the inability to achieve a balance between pain relief and development of constipation impairs HRQL and compromises effective pain management.17 A better understanding of OIC or more active HCP participation in monitoring and managing OIC may help with this balance.The symptoms of OIC may prompt patients to decrease the dose or stop using their opioid medication to relieve their constipation.The objectives of this study were (a) to describe HCP-reported understanding of his or her patients’ experiences with OIC, including the symptoms experienced, adequacy of treatment, and adequacy of pain management among patients receiving chronic opioid therapy for chronic noncancer pain; and (b) to evaluate the level of agreement or discordance in perception between patients and their HCPs of OIC’s impact on clinical outcomes.17 Briefly, patients with usual-care visits to primary care, pain, or other specialty clinics  were recruited. Data were collected from web-based patient surveys, retrospective chart reviews, and HCP questionnaires. Both patients and their respective HCPs completed surveys, and the responses on the HCP survey were based on HCP knowledge of his or her patients who completed the patient survey. The protocol and informed consent forms were reviewed and approved by institutional review boards and ethics committees to meet country- and site-specific requirements.This was a prospective, longitudinal, observational cohort study conducted in the United States, Canada, Germany, and the United Kingdom (NCT01928953). A detailed description of the methods of this study has been published.Patients aged 18 to 85 years who had been receiving daily opioid therapy for ≥ 4 weeks to treat chronic noncancer pain with presence of OIC in the 2 weeks before screening were eligible for enrollment. Patients were receiving a minimum total daily dose of 30 mg oral morphine or equianalgesic amounts of 1 or more other opioid therapies and were expected to continue on opioid therapy for ≥ 6 months. Presence of OIC was based on patient-reported symptoms. Patients were required to report laxative use if the number of BMs in the past 2 weeks was ≥ 3 per week, whereas those with < 3 BMs per week in the past 2 weeks were eligible regardless of reported laxative use. Patients who did not report laxative use were required to report at least 1 symptom of OIC  in the past 2 weeks. Patients who were unable or who refused to provide informed consent, who were unable to use or were without access to a computer with Internet connectivity to complete the web-based survey, or who had a history of chronic constipation were excluded.18 with 5 additional symptom items to assess nausea, vomiting, flatulence, GERD, and headache/migraine. Other standardized questionnaires in the patient survey included the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem,19 the EuroQOL 5 Dimensions,20 and the Global Assessment of Treatment Benefit, Satisfaction, and Willingness to Continue.21 The prospective, patient-reported component contained 1 baseline survey and 8 follow-up surveys over 24 weeks. Patients were nominally remunerated for their time to complete each survey. Retrospective chart reviews assessed patient medical history, pharmacotherapy (including opioid and laxative prescriptions), and health care resource utilization at 2 points in time—at baseline, which included the 12 months leading up to the baseline visit, and at the end of the 6-month prospective study period (week 24 visit), covering a total period of 18 months ,8 months . HCPs coAll analyses were performed with SAS software package 9.4 . Owing to the extensive nature of the objectives and number of analyses, descriptive statistics were applied. Summary measures such as means and standard deviations (SDs) for continuous variables and counts, frequencies, and percentages for categorical variables were reported; no statistical significance tests were applied. The correspondence of patient- and HCP-reported data was evaluated for all similar outcomes from these 2 databases, including OIC symptoms and treatment use. All data were analyzed without imputation for missing responses.Of the 617 patients initially recruited, 500 (81%) were enrolled and completed the patient baseline survey. Of those, 489 (98%) met criteria confirming the presence of OIC. Chart reviews were completed for 486 of 489 (99%) eligible patients at baseline and for 477 (98%) patients at week 24. HCP baseline and week 24 surveys were completed for 464 (95%) and 457 (94%) patients, respectively.Demographic and clinical characteristics of the overall patient population are shown in The mean (SD) number of BMs per week was 3.7 (2.9), and the mean (SD) number of spontaneous BMs per week was 1.4 (2.3) . On the Overall, 77% of HCPs reported that they discussed OIC symptoms and concerns with patients; however, only 65% were actually aware that the patients met criteria for OIC and only 58% of HCPs reported that patients complained of having too few BMs per week . A subseThe proportion of agreement between HCPs and patients on the presence of constipation at baseline was 61%. The most commonly reported symptoms rated as moderate to severe in intensity by patients were straining/squeezing to pass a BM (83%), BMs too hard (75%), flatulence (69%), incomplete BM (69%), bloating in abdomen (69%), painful BM (67%), and abdominal discomfort (64%); however, the proportion of HCPs who had observed or discussed each OIC symptom reported by the patient as being of moderate or greater severity ranged from 1% to 41% .In contrast with OIC symptomology, HCPs were well aware of patients’ pain severity, with both patients and HCPs reporting an average pain rating of 6.3. Nevertheless, HCPs overestimated how well patients managed their pain and OIC concurrently. Although 49% of patients reported that OIC interfered moderately or completely with the ability of their opioid medication to adequately control their pain, a majority (73%) of HCPs reported that their patients’ pain was mostly or adequately managed . This paOverall, 72% (n = 330) of HCPs reported that they had a follow-up visit or other consultation with their patients since the baseline visit. The patient-reported mean pain score was similar to that estimated by HCPs (5.9 vs. 6.0) at week 24 for pain in the last 24 hours and for pain in the last 7 days. Of the 330 HCPs who had a follow-up visit, 38% (n = 125) reported having discussed OIC symptoms and concerns with patients. Of these, HCPs responded that 75% of patients had taken laxatives to manage their OIC since the baseline survey and that about half (52%) had achieved moderate-to-complete satisfaction with laxative treatment. Almost half (46%) of the HCPs responded that treatments to relieve OIC were moderately to completely adequate. About half (54%) of HCPs expressed that OIC had little to no interference with the patients’ reports of HRQL. Of those visits in which the patients discussed OIC symptoms/concerns (n = 125), the most common treatment recommendations were to decrease the frequency of pain medication  or to take an opioid holiday .In this study, HCP-reported understanding of the patient experience with OIC and pain management when receiving chronic opioid therapy for chronic noncancer pain was assessed. Analyses of consistency between patient and HCP responses on web-based surveys were interpreted as evidence of limited or incomplete HCP awareness of the patient disease burden of OIC. Identical average pain ratings by HCPs and patients at baseline and similar average pain ratings by HCPs and patients at week 24 indicated that there appears to be clear communication between HCPs and patients regarding the level of pain experienced by the patients; however, OIC symptoms (at baseline), laxative use, satisfaction and benefit, and the impact of OIC on the impairment of pain management are not fully appreciated by HCPs. A potential factor playing into this disparity is a lack of communication about OIC between HCPs and patients that may contribute to a lack of awareness of the impact of OIC by HCPs and ultimately patient dissatisfaction. However, identification of reasons for this disconnect would be a topic for further health promotion research.Although most HCPs reported that they discussed OIC symptoms and pain severity with their patients, many were unaware of their patients’ OIC symptom severity, level of laxative use, and limited benefits with laxative use, which increased somewhat during the 6 months of the study. Despite inclusion in a study of OIC, there appears to be very little advancement in the conversation between patients and HCPs and very little improvement in HCP insight into the disease burden of their patients. Thus, patients’ ability to concurrently manage their pain and OIC is commonly underestimated by HCPs.The reasons for a lack of discussion of OIC symptoms may be related to both HCPs and patients. The HCPs may run out of time or believe the patients should initiate the conversation, and/or the patients may not mention OIC symptoms for fear of losing the opioid medication. There may be a lack of appreciation of the relationship between OIC and opioid use, a belief that OIC is a condition that should be self-managed and not shared with a physician, or embarrassment.Patients in this survey experienced chronic pain for an average of 9 years and used opioids for an average of 6 years. The gap in communication may have widened after being in this state for so long. A more proactive approach to prophylaxis, in which patients with chronic pain are targeted to have a conversation with their HCPs about constipation at the initiation of opioid therapy, may be a way to close this gap. It is also possible that the availability of better prescription therapies for OIC may also bring patients closer to their HCPs.17 Other studies have also shown that OIC causes patients to compromise their pain management to avoid constipation.13 In the current analysis, OIC interfered with patients’ pain management more than HCPs realized.A previously published analysis of baseline data from this study showed that OIC had a negative impact on patient activities of daily living, work productivity, overall HRQL, and, for some patients, ability to manage pain.25 In a longitudinal study in cancer patients, those with severe constipation scores were more likely than patients with mild or moderate constipation scores to initiate a discussion of their symptoms with a physician at first consultation.26 Studies in other indications point to a failure of physicians to initiate a conversation about disease symptoms and quality of life, race/ethnicity-related discordance between patients and physicians, and the presence of comorbid conditions24  as possible predictors of discordance between patient-physician perceptions.28 However, further research is needed to better understand the reasons for the discordance between patient-physician perceptions in patients with OIC.Discordance in patient-physician communication is not restricted to patients with chronic pain and OIC. For example, patient overreporting of symptom severity and underrating of HRQL compared with physician assessments has been observed in surveys of patients with cardiovascular disease, psoriatic arthritis, rheumatic diseases, and systemic sclerosis.29We hypothesized that differences may exist between patient and HCP perceptions of the burden of OIC on the symptom experience, the adequacy of pain management, the use and effectiveness of laxative therapy, and the day-to-day activities of patients receiving opioids for chronic noncancer pain.To improve patient care, the HCP treatment team may bridge this gap by including an assessment of OIC as part of routine appointments with patients receiving chronic opioid medication. Increasingly, patients are requested to complete brief questionnaires about their pain severity and other symptoms as part of the check-in process for routine-care visits. Inclusion of a single question to assess the presence of OIC may prompt physicians to follow up with patients about this issue. Clear treatment guidelines should be developed to establish best practices in the treatment of OIC when identified. A stepwise approach, with over-the-counter osmotic agents, surfactants, and/or stimulants as first-line therapy and prescription treatment options for those who do not respond to these therapies, should be considered. Clinical education and coordination of care by additional HCPs, including nursing staff, may add to the critical need to appreciate and proactively address the burden of disease. Development of a consensus definition of OIC and perhaps a validated assessment tool  in OIC and empirically based treatment guidelines are areas of further research that could close the gap. Chronic pain management and treatment side effects, including OIC, present complex challenges for patients and their providers.This study was subject to limitations, given that it involved patient self-reports and may have been influenced by cultural factors, differences in clinical practice, and, in some cases, small sample size.The importance and severity of OIC are perceived differently by patients and their HCPs, a discordance that complicates pain management and demonstrates a need for greater communication. These disparate perceptions indicate a need for clinical education and coordination of care by HCPs to improve understanding and proactively manage OIC in patients with chronic noncancer pain.