The functional score and morphological changes improved significantly after treatment in the C-LCCT group. However, there was no significant improvement in the TT group (p < 0.05). The C-LCCT showed significant pain, functional, and morphological improvement compared to TT. C-LCCT could be effective in improving the treatment outcomes of the traction technique in patients with cervical intervertebral disc disease.The newly developed cervical lordotic curve-controlled traction (C-LCCT) appears to be an ideal method to improve the treatment outcome in patients with cervical intervertebral disc disease. The purpose of this study was to investigate the treatment outcomes of C-LCCT including the functional and morphological changes of the cervical intervertebral disc compared to traditional traction (TT) with a randomized controlled trial design. A total of 40 patients with cervical intervertebral disc disease at the C5/6 level confirmed by magnetic resonance imaging were recruited and assigned to either the C-LCCT group or the TT group. The comprehensive health status changes of the patients were recorded using pain and functional scores  and morphological changes  before and after the traction treatment. Both groups showed a significant improvement in pain scores after traction ( Cervical traction has often been used as a conservative method to treat patients with neck pain in clinical settings . A varieImproper pressure loading on disc structures during the traditional traction (TT) technique may result in poor clinical outcomes. In the supine position, the lordotic curve is decreased under the effect of gravity on the cervical curve. When traction force is applied to the cervical spine in the supine position, it primarily straightens the natural lordotic curve rather than decompressing the intervertebral discs. Under TT, the posterior spinal structures, such as facet joints, and posterior longitudinal and interspinous ligaments are elongated more so than the anterior spinal structures . When trIn this prospective double-blind randomized controlled study, 40 patients were conveniently selected from the outpatient clinic. All patients gave informed consent for inclusion before they participated in the study. The study was approved by the institutional review board (IRB 04-2018-034).A total of 40 patients with cervical intervertebral disc disease on the C5/6 level confirmed by MRI were recruited from April 2018 to January 2019. The severity of the cervical disc disease was measured prior to inclusion based on the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Cobb angle on a lateral view of cervical spine using X-ray and central canal area using cervical MRI. The inclusion criterion was a diagnosis of C5/6 nerve root compression by cervical MRI and/or cervical radiculopathy confirmed by Electomyography (EMG), with lasting cervical pain of more than three months. Exclusion criteria were as follows: (1) central disc protrusion with cervical spinal cord compression; (2) acute inflammation; (3) malignant disease; and (4) unstable vertebrae or previous history of operation on spine. Patients were randomly assigned to two groups of C-LCCT and TT by a research physician using a computer-generated table of random numbers. None of the patients was aware of their group. The evaluations were carried out by a physician who was blinded to the treatment.The C-LCCT  was designed to maintain the natural lordotic curve by supporting the cervical curve at the C4–6 intervertebral disc space. The C-LCCT and TT methods are compared in Changes to functional improvements and pain scores of participants were measured before the first intervention and after the last treatment session. The ODI consists of 10 items that refer to activities of daily living that might be disrupted by pain. The items are as follows: 1. Pain intensity, 2. Personal care, 3. Lifting, 4. Walking, 5. Sitting, 6. Standing, 7. Sleeping, 8. Sex life, 9. Social life, and 10. Traveling. Each item is rated on a 6-point Likert scale. The total score is transferred onto a scale ranging from 0 to 100, where 0 indicates no disability and 100 indicates the worst possible disability . Pain in the trunk and lower extremities exacerbated during activities of daily living was measured using the VAS, which ranges from 0–10. The patients were asked to place a mark along the line to denote their pain level; 0 reflected “no pain” and 10 reflected the “worst pain” .As shown in We assessed the changes in the area of the cervical central canal before and after cervical traction. Using the MR T2-weighted images, the axial image with the greatest disc level associated with the greatest neurologic compression was selected for measurement. In this study, the C5/6 intervertebral disc level was selected. Digital measurement of the central canal area outline was performed by tracing the boundaries of the dural cross-sectional area in the axial MRI at the C5/6 disc level . MeasureThe evaluations of pain (VAS), function (ODI), and morphology  were conducted within two days before the first treatment session and after the last treatment session.p < 0.05. SPSS software ver. 22.0  was used for all statistical analyses. Prior power calculations indicated that 18 patients were needed in each group to detect differences in cervical neck pain between the groups at 80% power and 5% significance. A two-tailed test was performed with an expected effect size of d = 0.8 based on a pilot study of 10 patients who underwent the same intervention between November 1, 2017, and January 28, 2018. Data were analyzed using a paired t-test and independent t-test. The significance level was set at The demographic data of the patients are presented in The pain and functional changes are presented in The morphological changes after treatment are shown in p < 0.01). However, there was no significant change in the central canal area in the TT group after treatment (p > 0.05).The change of the central canal area in cervical spine MRI was significantly greater in the C-LCCT group . The equal distribution of traction force in C-LCCT (anteriorly and posteriorly) ideally elongates the intervertebral disc space without generating needless muscle tension and thereby increases its efficiency. Based on our results, maintenance of the lordotic curve is essential to improve the therapeutic outcomes in patients treated with TT.In our study, the therapeutic effect of C-LCCT was significantly greater than that of TT in terms of pain, functional, and morphological outcomes. Both groups showed significant improvement in pain after treatment . HoweverDespite the favorable results, our study has several limitations. First, various conditions associated with spinal nerve compression were not included in this study. The severity of nerve root compression and the structural diversities may influence treatment outcomes. Further studies investigating various conditions of disc diseases are needed. Second, a long-term clinical study is desirable to corroborate the preliminary findings of short-term efficacy at five weeks after treatment. Studies establishing the long-term effects of C-LCCT will clarify the value of the clinical application of traction.Consistent with our original hypothesis that appropriate traction force distribution is key to maintaining the lordotic curve, we found significant successful outcomes using C-LCCT. Compared to TT, our randomized double-blind controlled study showed statistically significant differences in pain, functional scores, and morphological changes. Additional samples including diverse patient groups and modified treatment guidelines are needed to generalize our results. Based on our results, the newly invented C-LCCT is recommended as a reliable and conservative method to alleviate spinal nerve compression in patients diagnosed with cervical intervertebral disc disease.Maintenance of the lordotic curve appears to be one of the key factors to improve treatment outcomes of cervical traction in patients with cervical nerve root compression. Based on our results, we suggest C-LCCT as a reliable treatment option available under clinical settings.


Orthopaedic surgeons are increasingly aware of deleterious effects of the opioid epidemic and the association between overprescription and diversion toward nonmedical opioid use or substance abuse. Opiate prescriptions at the time of hospital discharge have been identified as target for intervention. This study describes the successful outcome of a goal-directed intervention aimed at decreasing opioid overprescription by providing routine feedback to providers regarding their prescribing patterns.The amount of opioid medications, quantified as oral morphine equivalents (OMEs), provided to opioid-naive adult patients on discharge after orthopaedic surgery was prospectively collected. As part of an institutional quality improvement initiative, medical providers received reports every 2 months detailing median discharge OMEs prescribed, trended over time. After 6 months, a retrospective comparison was done between preintervention and intervention patient cohorts.P < 0.001). Despite these opioid medications, opioid refill rates during the first 90 days after discharge did not markedly change between groups.There were 401 patients in the preintervention cohort and 429 patients in the intervention cohort. Both groups were similar in regard to age, sex, rates of depression, surgical time, length of stay, orthopaedic subspecialty, and inpatient opioid requirement before discharge. Patients in the intervention cohort were prescribed markedly fewer opioid medications by 25%, equivalent to 20 tablets of 5-mg oxycodone IR (450 versus 600 OMEs, It is critical to judiciously treat postoperative pain while avoiding opioid overprescription. This study demonstrated the outcome of a goal-directed initiative to decrease overprescription of opioid medications. The initiative reduced discharge opioid prescriptions yet did not increase the risk of requiring a prescription refill in the postoperative period. This indicates that such an approach can result in opioid reduction, while still providing appropriate care and pain control for patients. Between 1999 and 2015, the number of opioid-related mortalities has tripled, with an estimated 33,000 opioid-related mortalities in 2015, according to CDC data. In addition, opioid overdose is responsible for roughly 53,000 nonfatal overdose hospitalizations a year.10 Clearly, the overconsumption and abuse of these medications poses a notable public health and socioeconomic burden. A recent report estimated that the economic cost of nonmedical opiate use is in excess of $50 billion annually.11Multiple studies have demonstrated that surgeons tend to overprescribe opioid medications when treating postoperative pain.13 However, while opioid medications can be a valuable part of a post-operative pain control regimen, there is substantial evidence that excessive provision of these medications is related to the recent rise of opioid-related complications.10The rise in the prescription and consumption of opioid medications in America is multifactorial, but is likely related to a historical approach to management of pain as the “fifth vital sign,” efforts to maximize patient satisfaction, and a desire to proactively manage pain.14 This provides a significant opportunity to improve and thereby decrease the risk of opioid-related complications in millions of patients who undergo orthopaedic procedures annually. Several approaches have been suggested to minimize opioid overuse or abuse. First, some authors have identified preoperative risk factors for overconsumption and complications after orthopaedic surgery.1516171819 Second, a focus on the utilization on non-narcotic analgesia perioperatively has been endorsed as a strategy to reduce opioid exposure, ostensibly reducing the risk of chronic opioid use.20-22 Finally, the overprescription of opioid medications after discharge has been identified as a target for intervention.23Orthopaedic surgeons have been identified as the third highest prescribers of opioids in the United States.25 Others have found notable variation and patterns of overprescription following common surgical procedures.2 As a corollary, decreasing the magnitude of opioids on discharge may reduce the potential for diversion without necessarily increasing the need for medication refills. Although the following may seem counterintuitive, the finding has been observed; one recent study demonstrated successful curtailment of discharge opioid medications after incorporation of consensus guidelines after elective hand surgery, without an associated rise in refills.26 The following is likely related to the fact that current prescribing practices far exceed the quantities actually required for adequate pain control after common orthopaedic surgeries.Previous studies have demonstrated that increased magnitude of opioids provided on discharge does not influence the likelihood that a patient will require a medication refill.Recognizing the importance of judicious opioid prescription practices, a quality improvement (QI) initiative was conducted at our institution with the goal to globally decrease discharge opioid prescription quantities by 10%. The QI project used a report sent every two months, which showed providers the median discharge oral morphine equivalents (OMEs) per patient, over time and relative to the 10% reduction goal. In addition, additional data were presented including median discharge OMEs by subspecialty and by individual provider (deidentified). The purpose of this study was to review the efficacy of the QI project implementation, in regard to both the overall quantity of opioids prescribed (in OMEs), and also assess the effect on postdischarge refill rates. The null hypothesis was that the incorporation of the intervention would not change the quantity of opioids prescribed.This study was conducted at a single tertiary-care, academic hospital. As part of an institutional QI program, we sought to decrease the postdischarge prescription of opioid medications postoperatively over a 6-month period . Specifically, the goal was to reduce the median quantity of opioid medications by 10% compared with the 6-month period before the QI initiative . The goal reduction of 10% was determined after review by the institution's Quality and Safety office. This magnitude of reduction was believed to represent a notable improvement in responsible prescribing, without compromising postoperative pain control regimens or undertreating postoperative pain.After obtaining Quality and Safety as well as institutional review board approval, the amount, type, and regimen of opioid medications prescribed at discharge were obtained prospectively for all opioid-naive patients undergoing orthopaedic surgery between July 1, 2017, and December 31, 2017. Pediatric patients (younger than 18 years) and patients discharged in under 24 hours were excluded. All opioid regimens were converted into OMEs. If patients were prescribed multiple opioids at discharge, each prescription was converted separately and then combined to determine the total amount of OMEs prescribed. Every 2 months, prescribers within the department  received an e-mail notification quantifying the overall median discharge opioid prescriptions per patient and summarizing the department's progress toward reaching the established goal After the 6-month study period , a retrospective comparison was done between patients treated during the initiative (“intervention cohort”) and patients treated the 6 months before the initiative (“preintervention cohort”). Demographic and inpatient data as well as predischarge opioid requirements, discharge prescription quantities, and postdischarge refill rates were then compared between these cohorts to characterize the effect of this opioid-reduction intervention.U test, and categorical variables  were compared with the chi-square test. All statistical analyses were done on STATA software , with significance set to P < 0.05.Continuous variables  were compared with the Mann-Whitney A total of 1,917 opioid-naive patients required admission after an orthopaedic procedure at our single tertiary-care institution between January 1, 2017, and December 31, 2017. Pediatric patients (N = 130) and patients taking opioids before surgery (N = 957) were excluded. Thus, 830 opioid-naive adults were considered in this study: 401 patients who underwent surgery between January 1, 2017, and June 30, 2017 (“preintervention cohort”) and 429 patients who underwent surgery between July 1, 2017, and December 31, 2017 (“intervention cohort”).P = 0.74), sex , rates of depression , surgical time , length of stay , and operating orthopaedic subspecialty (P = 0.91)  (Table P < 0.001) , 31 to 60 days , and 61 to 90 days  . For reference, a difference of 150 OMEs translates to 20 pills of 5-mg oxycodone IR per patient. Despite a successful reduction in total OMEs prescribed on discharge, we did not observe a notable increase in the need for refills. These trends suggest that such a strategy may be effective in reducing the potential for diversion without undertreating postoperative pain. Previous studies have shown that physicians may commonly prescribe more than double the amount consumed on average after common orthopaedic procedures.31 The following suggests that additional reduction is achievable and appropriate without compromising postoperative care.Our study demonstrated the efficacy of an institutional QI initiative to decrease the OMEs of opioid prescriptions on hospital discharge. We found that a proactive approach toward curtailing overprescription was effective in reducing the quantity of opioid medications, when comparing the intervention group with the preintervention group. Furthermore, the magnitude of reduction was substantial , the initiative demonstrated its efficacy in achieving its goal.One facet of the intervention within the QI initiative was the use of routine updates sent through e-mail to providers every 2 months. In the update, each individual was provided information regarding recent prescribing patterns as an aggregate over time Figure . This upOur findings should be interpreted in the context of several important limitations. The study was done at a single academic teaching hospital in a large metropolitan area. As a result, the findings may not be generalizable to all patient cohorts or hospitals/physicians. Second, the intervention group was compared with a historical cohort (patients who underwent surgery in the 6 months before implementation of the QI initiative), and so, historical bias may be present. However, we found that there were no notable demographic differences between patient groups, and to the best of our knowledge, there were no other protocol changes to analgesia/perioperative pain management during this period which may have markedly affected findings. Generally, a multimodal approach to pain management had been protocolized across most services for years before the intervention. However, this multimodal approach has not been standardized between services. This lack of standardization may have contributed to the finding that Spine and Sports Medicine divisions did not demonstrate notable opioid reduction during the study period.33In addition, although we were able to record the provision of opioid medications on discharge and refills provided in clinic, through the use of a unified EMR, we were not able to account for opioid medications provided by an outside physician group, urgent care, or emergency department. Although we found that there were no notable differences in refill rates, we were not able to report on patient pain scores, satisfaction, or patient perceptions of their pain relief. These outcomes will be important in future studies, to ensure that decreases in pain medication prescription do not come at the cost of sensible pain management. In this study, refill rates were used as a proxy for pain control after discharge, although refill rates may be confounded by several variables such as limited patient access, hesitation to provide refill prescriptions, and opioid acquisition through diversion from friends or family.30, in a study of outpatient upper extremity surgery, found that their prescribing patterns were far in excess of patient consumption. In their study of 250 patients (most received 30 opioid pills on discharge), an average of 19 pills was left unconsumed, representing 4,639 leftover opioid analgesic pills available for misuse or diversion. Oxycodone, hydrocodone, and propoxyphene accounted for more than 95% of the discharge medications. Kumar et al31, in a study of outpatient shoulder surgeries, also found that patients had notable leftover medication. In their study, patients 90-days post-operative after shoulder stabilization/Bankart repairs had a median of 37 unused opioid pills, compared to a median of 60 prescribed at discharge. Oxycodone, hydrocodone, and codeine were the mostly commonly prescribed medications. This finding was corroborated in a study examining opioid utilization after outpatient knee arthroscopy.15 Ruder et al34 done a retrospective study of opioid-prescribing practices in a trauma cohort. They found that large quantities of opioids  were provided to patients after discharge, including to patients believed to be at high risk of misuse and polysubstance abuse. Notably, in their study cohort, nearly one-fifth of patients were prescribed extended-release oxycodone on discharge.Several studies have demonstrated that current opioid prescription practices are excessive. Rodgers et al35-37 Therefore, some level of standardization may be effective, and recently, the use of prescription “maximums” has been endorsed as a possible strategy to reduce outliers in overprescription.38 The efficacy of standardization was demonstrated in recent study, in which the authors found that acceptance of a postoperative prescribing guideline was successful in reducing the quantity of OMEs after outpatient hand surgery.26 Importantly, the authors of that study found that the implementation group was not at higher risk of requiring secondary opioid medication refills. Our study extends on this finding, demonstrating that for a large number of patients across orthopaedic subspecialties, implementation of opioid reduction goals was effective in reducing opioid prescription without influencing refill rates.In the absence of widely accepted guidelines, variability in prescribing practices will persist. Previous studies have shown that there is substantial variation in the provision of opioid medications following common surgical procedures.Future study should focus on the development of procedure- and patient-specific guidelines to optimize prescription practices. The optimal strategy would be to provide the lowest possible dose while minimizing the need for secondary opioid refill prescriptions. Such a strategy would provide adequate analgesia for postoperative patients while decreasing the risks associated with excessive opioid use and diversion. A large study examining the “optimal” OMEs to prescribe for commonly done orthopaedic procedures would be very helpful to provide guidance to physicians managing postoperative pain. Any guideline, ideally, would also incorporate patient risk factors for higher opioid requirement/use/abuse, including previous exposure to opioids, use of long-acting narcotic medications, and/or other pertinent medical or psychosocial risk factors. In addition, the inclusion of patient pain scores, satisfaction, and perception of pain will be helpful to ensure that efforts to curb opioid overprescription do not come at the expense of adequate postoperative analgesia. These results of this study, which show a successful reduction in opioid prescriptions through the use of a QI initiative, are encouraging that such efforts can be successful without compromising care.


After controlling for confounders, high CCI was associated with longer LOS  and increased likelihood of in-hospital death . The adjusted median, 25th, and 75th percentile costs were AUD$2483 (26.1%), AUD$1446 (28.1%), and AUD$3140 (27.9%) higher for patients with high CCI than for those with low CCI. Among older adults hospitalised for acute stroke, higher global comorbidity (CCI ≥ 2) was associated adverse clinical outcomes. Measures to better manage comorbidities should be considered as part of wider strategies towards mitigating the social and economic impacts of stroke.The burden of comorbidity among stroke patients is high. The aim of this study was to examine the effect of comorbidity on the length of stay (LOS), costs, and mortality among older adults hospitalised for acute stroke. Among 776 older adults  hospitalised for acute stroke during July 2013 to December 2015 at a tertiary hospital in Melbourne, Australia, we collected data on LOS, costs, and discharge outcomes. Comorbidity was assessed via the Charlson Comorbidity Index (CCI), where a CCI score of 0–1 was considered low and a CCI ≥ 2 was high. Negative binomial regression and quantile regression were applied to examine the association between CCI and LOS and cost, respectively. Survival was evaluated with the Kaplan–Meier and Cox regression analyses. The median LOS was 1.1 days longer for patients with high CCI than for those with low CCI. In-hospital mortality rate was 18.2% (22.1% for high CCI versus 11.8% for low CCI,  Non-communicable chronic diseases are prevalent among older people . Data frMultimorbidity is associated with higher utilisation of healthcare services and polypharmacy and places a significant burden on the healthcare system . A poor Cerebrovascular diseases, including stroke, are important causes of global morbidity and mortality. In 2013, stroke was the second most common cause of death  and the third most common cause of disability worldwide  . ConsequUp to 90% of stroke sufferers have one or more comorbid conditions and almost a quarter have ≥5 CMCs ,11. CurrThe Charlson Comorbidity Index (CCI) has been demonstrated in several studies to be useful for predicting the prognosis of real-world patients with comorbidities ,18. HighWe undertook a retrospective analysis of the records of all patients admitted for acute stroke between 1 July 2013 and 31 December 2015 to the Alfred Hospital, a large tertiary hospital with an established stroke unit in Melbourne, Victoria. Stroke was defined by the International Classification of Diseases, Version 10, Australian Modification (ICD-10-AM) codes /acquired immune deficiency syndrome [AIDS] (weight = 6) . In addiχ² test for proportions, Student t-test for means, and Kruskal–Wallis rank test for the comparison of medians. Kaplan–Meier survival curves and log-rank test were used to compare in-hospital mortality between groups. A Cox proportional hazards model was then derived and adjusted for baseline clinical and sociodemographic parameters and year of admission. The test of proportional hazards assumption was performed for model calibration. In the multivariable Cox proportional hazards model, the only variable violating the proportional hazards assumption was stroke type, and therefore this was included as a stratifying factor  and high [CCI ≥ 2]  . Unless The study received approval from the Alfred Hospital Human Research Ethics Committee.A total of 776 older adults was hospitalised for acute stroke between 1 July 2013 and 31 December 2015, of whom 66.2%, 27.3%, and 6.5% had ischaemic, haemorrhagic, and undetermined stroke, respectively. The mean age of the cohort was 80.1 (SD ± 8.3) years and 46.7% were female. More than half (50.4%) were married or in a de-facto relationship. Approximately 3.0% were patients from an aged care residential facility. Overall, 48.6% were born outside of Australia and 10.6% were non-English-speaking and required an interpreter. Less than 1% of the cohort identified themselves as Aboriginal or Torres Strait Islander. Similarly, <1% were admitted as private patients. The percentage of the study cohort with hypertension, atrial fibrillation, congestive heart failure, metastatic cancer, renal disease, diabetes with complications, or current smokers was 65.3%, 24.2%, 6.7%, 3.4%, 10.7%, 10.4%, and 3.2%, respectively. The mean CCI of the cohort was 2.21 (SD ± 2.2) and the median was 2.0 (IQR 0–3). The percentage of patients with high CCI score (≥2) was 61.9%. One in ten (10.3%) of the patients were admitted to the ICU. p-value for difference = 0.6757. For undetermined stroke, the median LOS was much lower . The median LOS in patients with a low CCI (0–1) was 4.81 (IQR 2.85–7.71) days compared to 5.88 (IQR 3.27–9.44) days in patients with a high CCI (≥2) . After adjusting for potential confounders in the NBR model, a high CCI score was associated with a 35% higher likelihood of increased LOS compared to a low CCI score .p-value for difference = 0.8155. The unadjusted median cost among patients with undetermined stroke was much lower . Patients with a low CCI score (0–1) incurred lower median unadjusted hospital costs  compared to those with a high CCI score (≥2)  (p = 0.0001). When adjusted for potential confounders , ICU stay, and treatment within stroke unit), the median hospital cost was AUD$2481 (26.1%), and 25th and 75th percentile costs were AUD$1446 (28.1%) and AUD$3140 (27.9%), respectively, which was higher in the high CCI (≥2) group compared to the low CCI group . The unadjusted proportion of patients with undetermined stroke who died was 24.0%. The proportions of patients with a low CCI score (0–1) and a high CCI score (≥2) who died were 11.8% and 22.1%, respectively .Overall, in-hospital death occurred in 18.2% of the study cohort. The unadjusted in-hospital mortality rate varied by stroke sub-type: 12.7% in patients with ischaemic stroke and 30.2% in those with haemorrhagic stroke  (p = 0.003) after adjusting for key clinical and sociodemographic confounders as listed in Patients with low CCI scores had better survival rates compared to patients with high CCI scores ( 0.0265) . A high In the present study, we found that a high CCI score was associated with increased LOS, higher hospital costs, and a greater likelihood of in-hospital death. Specifically, patients with a high CCI score (≥2) had a 1.1 day longer LOS (35% increased risk) compared to those with a low CCI score (0–1). The adjusted median hospital cost for patients with high CCI was 26.1% (AUD$2481) higher than for patients with low CCI. A high CCI score was also associated with 91% increased risk of death compared to a low CCI score.Few studies have examined the relationship between comorbidities and LOS, mortality, and, in particular, healthcare costs among older adults hospitalised for acute stroke. Our study highlighted the substantive clinical and economic impact of comorbidities among a diverse population of older adults from a developed country with a universal healthcare system.Globally, older adults have a higher risk of stroke mortality than younger individuals ,27,28,29The ageing process, as represented by chronically elevated pro-inflammatory markers, is a leading risk factor for major CMCs such as cardiovascular diseases, dementia, and chronic kidney disease . The CCIOur results also indicate that CCI is associated with longer LOS and higher hospitalisation costs in Australia. CCI has previously been found to predict LOS in stroke patients , as wellThe relationship between the CCI score and multiple outcomes  as observed in this study supports the notion that CCI can be adapted for risk stratification, particularly when negotiating bundled payments ,42, as iThere were several limitations to our study that warrant mention. First, we analysed only administrative hospital data that were not collected for research purposes. The data may be subject to coding errors or omissions and inaccurate classification of diagnoses and complications. Secondly, information was not available for important covariates such as body mass index (BMI), disease severity, and laboratory and imaging results. Thirdly, given that our sample population was selected from a single hospital, selection bias may limit the generalisability of our findings. Fourthly, the CCI did not account for the effects of gradations of disease progression and severity. Furthermore, because of the differences in our study population and that from which the original CCI was developed, the performance of the CCI as a prognostic variable might not be the same . FinallyAmong older adults hospitalised for acute stroke, high global comorbidity (CCI ≥ 2) was associated with increased LOS, costs, and mortality. The adaptation of CCI within acute care settings has the potential to offer a rapid and reliable approach to identifying patients likely to experience adverse outcomes who may benefit from closer monitoring. Measures to address comorbidities need to be considered as part of wider strategies for reducing the social and economic impact of stroke.


Mirizzi syndrome is a condition difficult to diagnose and treat, representing a particular “challenge” for the biliary surgeon. The disease can mimic cancer of the gallbladder, causing considerable diagnostic difficulties. Furthermore, it increases the risk of intraoperative biliary injury during cholecystectomy. The aim of this study is to point out some particular aspects of diagnosis and treatment of this condition. The clinical records of patients with Mirizzi syndrome, treated in the last five years, were reviewed. Clinical data, cholangiograms, preoperative diagnosis, operative procedures, and early and late results were examined. Eighteen consecutive patients were treated in the last five years. Presenting symptoms were jaundice, pain, and cholangitis. Preoperative diagnosis of Mirizzi syndrome was achieved in 11 patients, while 6 had a diagnosis of gallbladder cancer and 1 of Klatskin tumor. Seventeen patients underwent surgery, including cholecystectomy in 8 cases, bile duct repair over T-tube in 3 cases, and hepaticojejunostomy in 4 cases. Two cases (11.1%) of gallbladder cancer associated with the Mirizzi syndrome were incidentally found: a patient underwent right hepatectomy and another patient was unresectable. The overall morbidity rate was 16.6%. There was no postoperative mortality. An ERCP with stent insertion was required in three cases after surgery. Sixteen patients were asymptomatic at a mean distance of 24 months (range: 6-48) after surgery. Mirizzi syndrome requires being treated by an experienced biliary surgeon after a careful assessment of the local situation and anatomy. The preoperative placement of a stent via ERCP can simplify the surgical procedure. Mirizzi syndrome was firstly reported by Pablo Luis Mirizzi 1893-1964), one of the major biliary surgeons in the past century. Mirizzi was born in Cordoba (Argentina) from Italian parents. He spent all his academic career in his hometown, where he left a deep mark 893-1964,. He is m(i) Type I, "classic" Mirizzi syndrome.(ii) Type II cholecystocholedochal fistula with two subtypes: (a) diameter less than 50% of the CBD and (b) diameter more than 50% of the CBD.(iii) Type III, with cholecysto-enteric fistula without (a) or with (b) gallstone ileus.However, many authors continue to use the first classification of Csendes  which, bThis need for an accurate classification is related to the high frequency of the syndrome in South America, where it occurs in about 5% of gallstones, while in Western countries its incidence is about 1% .Mirizzi syndrome is a condition difficult to diagnose and treat, representing a particular challenge for the biliary surgeon aware of the risk for the patient. The syndrome can mimic gallbladder cancer, but it also represents a precancerous condition, consequently causing considerable diagnostic difficulties. At the same time, because of the significant increase in the risk of intraoperative biliary injury during cholecystectomy, it is a very dangerous condition. At present, a standard treatment of Mirizzi syndrome is not yet well defined, due to the heterogeneous clinical presentation. Surgical treatment should be planned after a careful assessment of the local situation and anatomy. During the past five years we observed some consecutive cases of Mirizzi syndrome, which led us to review this field in an attempt to point out some particular aspects of diagnosis and treatment of this challenging condition.Detailed clinical records of patients with diagnosis at discharge of Mirizzi syndrome, treated in our unit between January 1st, 2012, and December 31st, 2016, were reviewed. The following data were considered: sex and age of the patients; presenting symptoms and previous treatments; preoperative radiological investigations; preoperative diagnosis; surgical procedures performed; postoperative course ; findings at pathological examination. Follow-up data, obtained by direct clinical observation, laboratory findings (liver function tests), and need for further treatment, were also recorded.In the last 5 years, 18 consecutive cases of Mirizzi syndrome were treated in our unit and they represented 1.54% of 1.165 cholecystectomies performed in the same period. Eleven patients were male and 7 were female with a mean age of 63.4 years (range: 25-90 years). Presenting symptoms were obstructive jaundice in 14 patients, colic pain in 3 patients, and acute cholangitis in one patient. Preoperative imaging included ultrasonography (US) in all cases, Computerized Tomography (CT) in 12 patients, and Magnetic Resonance Imaging (MRI) in 10 patients. Fourteen patients underwent a preoperative ERCP; in all cases a stricture was found and, consequently, one or more stents were positioned in the CBD. Percutaneous cholangiography was performed in 2 patients and a percutaneous drainage was placed preoperatively. After diagnostic investigations, a diagnosis of Mirizzi syndrome was achieved in 11 patients, a diagnosis of gallbladder cancer was achieved in 6 patients, and a Klatskin tumor was diagnosed in one patient.Seventeen patients underwent surgery. Eight patients with type I Mirizzi syndrome underwent a simple cholecystectomy, leaving in place the portion of the infundibulum adherent to the CBD. In three cases of Mirizzi type II, after cholecystectomy, a bile duct repair over T-tube was made. In other three cases of Mirizzi type II, an excision of the gallbladder and involved CBD with hepaticojejunostomy on Roux-en-Y loop was performed. The patient with type II Mirizzi presenting with acute colangitis was treated urgently with biliary drainage by ERCP and two months later underwent cholecystectomy and hepatico-jejunostomy. In patients with preoperative erroneous diagnosis of gallbladder cancer or Katskin's tumor, frozen sections and definitive histological examination clarified the diagnosis of Mirizzi syndrome. On the contrary, an unexpected gallbladder cancer associated with the Mirizzi syndrome was diagnosed intraoperatively in two patients: a 68-year-old man who received an explorative laparotomy for an unresectable cancer with peritoneal carcinomatosis and a 52-year-old female who underwent right hepatectomy with CBD excision for gallbladder cancer involving the CBD. Finally, a 90-year old man, who had initially received a diagnosis of gallbladder cancer, was re-evaluated with CT scan and MRI eighteen months later and was diagnosed as Mirizzi type-I syndrome. This patient did not undergo surgery and was treated by percutaneous drainage.The overall morbidity rate was 16.6% (one case of post-ERCP pancreatitis and two cases of wound infection after surgery). There was no postoperative mortality. The 8 patients who underwent simple cholecystectomy enjoy good health with normal liver function tests. The three patients with CBD reconstruction over T-tube developed cholestasis after T-tube removal, due to the occurrence of a postoperative stricture: all cases were successfully treated with ERCP and multiple plastic stents insertions. The 4 patients who had undergone hepaticojejunostomy enjoy good health with normal liver function tests. The patient with unexpected finding of gallbladder cancer died three months after surgery. The patient who underwent right hepatectomy is alive six months after surgery and is being treated with chemotherapy. The patient with incorrect initial diagnosis of gallbladder cancer enjoys good health and replaces his percutaneous drainage at three month intervals. Clinical data are summarized in The review of this clinical experience on Mirizzi syndrome allows some considerations regarding the diagnosis and treatment of the disease. In this series, patients with Mirizzi type I represented the majority of cases 11/18=61%). Preoperative diagnosis was correct in 11 cases out of 18 (61%), while the unexpected finding of cancer occurred in two cases (11%) a significant percentage, considering that unexpected cancer is usually found in less than 1% of cholecystectomies /18=61%. , 13. In Diagnostic difficulties are explained by the different clinical presentations of the disease. The classic presentation is obstructive jaundice without painful symptoms and with evidence, at ultrasonography, of a gallstone impacted in the gallbladder infundibulum and determining an external obstruction of the CBD with consequent dilation of the intrahepatic biliary tree. The diagnosis needs to be confirmed by CT or MRI and, finally, by surgery with histological examination. In these cases, in which it may be a Mirizzi syndrome type I or type IIa according to Béltran classification , it is sIn type I Mirizzi syndrome, surgical treatment involves removal of the gallbladder leaving in place the portion of the infundibulum adherent to the CBD. In this way, the patency of the CBD is ensured by the presence of the stents. In type IIa Mirizzi syndrome the gallbladder is partially removed and part of the infundibular wall is used for the closure of the CBD. After surgery, stents can be eliminated spontaneously or subsequently removed. This modality of treatment is preferable to the CBD reconstruction over T-tube. In fact, after the removal of the T-tube, a stricture can appear requiring further endoscopic treatment, as in three cases of this series. The 4 cases of Mirizzi type IIb in our series received hepaticojejunostomy with an uneventful clinical outcome at follow-up. Regarding laparoscopic surgical approach, there are different opinions in the literature. Although laparotomy is considered a safer approach in the management of patients with Mirizzi syndrome, some authors , 16 repoAnother frequent clinical picture of the Mirizzi syndrome is that of a stricture mimicking biliary cancer. When the associated inflammatory process is predominant, it involves the CBD and mimics a neoplastic stricture at the MR-cholangiography . PatientA clinical onset with acute cholangitis is typical of type II Mirizzi syndrome: in these cases, diagnosis is facilitated by ERCP that allows to reduce the pressure in the CBD by positioning of nasobiliary drains or stents. However, surgery still represents the definitive solution: the choice between cholecystectomy with fistula closure and hepaticojejunostomy should be evaluated by the surgeon taking into account the extent of the CBD involvement, according to the Béltran categories .In some cases, the Mirizzi syndrome can represent an unexpected intraoperative finding and the main risk is accidental bile duct injury. This happens when the surgeon wants to complete the cholecystectomy “at any cost” without previous identification of the CBD. On the contrary, the main goal must be to avoid any injury to the bile ducts and, therefore, the placement of a cholecystostomy may be an appropriate and justified measure as a bridge solution before referring the patient to a hepatobiliary center. Alternatively, it may be carried out a subtotal cholecystectomy, leaving in place a portion of the infundibulum adherent to the CBD, after removing the stones. Testini and coworkers suggested a decision algorithm for emergency in nonspecialized centers .Mirizzi syndrome continues to be a disease of difficult diagnosis and treatment. The general surgeon without long experience in hepatobiliary surgery should refer the patient to a specialized hepatobiliary surgical center. It is difficult to standardize the treatment of the disease since clinical presentation and anatomical situations are very variable . It is important, however, for surgeons to know the disease and the possible intraoperative challenging situations. In patients with Mirizzi syndrome type I, the best management seems to be the preliminary placement of one or more stents by ERCP, followed by cholecystectomy leaving in place a small portion of the gallbladder adherent to the CBD. It is advisable to leave the stent in the postoperative period and remove it after nearly 2 months. In the occurrence of a postoperative stricture, endoscopic treatment with positioning of multiple plastic stents is recommended until resolution. In Mirizzi syndrome type II subtype a (according to Béltran classification), treatment may be similar to type I; however, a close attention to the diameter of the residual CBD is required during the reconstructive phase. In type IIb, the definitive solution appears to be hepaticojejunostomy. As for the type of surgical approach (laparoscopy or laparotomy), laparoscopy is reserved to a very experienced surgeon. However, in our opinion, laparotomy allows better evaluation of biliary anatomy, avoiding any risk of bile duct injury and with the advantage of a more accurate surgical procedure.


A randomized controlled trial is mandatory before proposing such treatment.Endometriosis concerns more than 10% of women of reproductive age, frequently leading to chronic pelvic pain. Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) induces an analgesic effect. This effect on chronic pelvic pain is yet to be evaluated. The objective of this study was to assess the feasibility and effect of rTMS to reduce pain and improve quality of life (QoL) in patients with chronic pelvic pain due to endometriosis. This pilot, open-labelled prospective trial examined treatment by neuronavigated rTMS over M1, one session per day for 5 consecutive days. Each session consisted of 1.500 pulses at 10 Hz. We assessed tolerance, pain change and QoL until 4 weeks post treatment with a primary endpoint at day 8. Twelve women were included. No patients experienced serious adverse effects or a significant increase in pain. Nine women reported improvement on the Patient Global Impression of Change with a reduction in both pain intensity and pain interference (5.1 ± 1.4 vs. 4.1 ± 1.6,  Endometriosis is a very frequent pathology, concerning 10% of women of reproductive age and at least 20% of women with pelvic pain . HormonaRepetitive transcranial magnetic stimulation (rTMS) has been proven to be effective for various pain types, nociceptive, neuropathic and even nociplastic ,9,10,11,The aim of our pilot study was to assess the feasibility, safety and potential efficacy of rTMS treatment for refractory pelvic chronic pain due to endometriosis.The protocol ENDOSTIM is a registered Clinical Trial (NCT03204682) and received approval from the Southeast Committee for the Protection of Persons VI . We performed an open-labelled, prospective trial evaluating the feasibility and tolerance of five rTMS sessions over 5 consecutive days in endometriosis patients with chronic pelvic pain.Inclusion criteria included patients with histologically confirmed endometriosis experiencing at least one painful symptom related to endometriosis  with an average numeric rating scale > 4/10 for at least 4 days out of 7 for at least 3 months, continued hormonal treatment failure, adequate oral and written French, and the possibility of monitoring for the duration of the study (4 weeks). Patients were experiencing failure of both drug and surgical treatment. Written informed consent was obtained from each patient. Exclusion criteria included: prior treatment with rTMS, contra-indication to rTMS, another more severe pain than that associated with endometriosis, patients under guardianship, or those unable to understand informed consent.Once enrolled, a clinical evaluation of symptoms associated with endometriosis  was performed. Patients completed an electronic “daily pain” survey for 28 days before the first rTMS session and a second “daily pain” survey for 28 days after this session, in order to evaluate response to treatment .The primary outcome involved the percentage of patients undergoing the five rTMS sessions, without serious adverse effects and without significant increase in pain at day 8 (D8) when compared to the pain level assessed over the previous 4 weeks. A variation of 10% was considered as significant . PatientSecondary outcomes took into account several measures of chronic pain caused by endometriosis. Firstly, the variation between the mean pain before inclusion and day 8  was measured using a visual analogue scale with a range from 0 to 100. The next variations in survey scores were analyzed before stimulation and at D8 and D28  ) with BrOther emotional aspects of chronic pain were evaluated from responses to the following questionnaires: The Beck Questionnaire (Depression) ; The StaEach volunteer underwent brain MRI  prior to the first stimulation session to rule out brain abnormalities and to facilitate the neuronavigation procedure.Magnetic stimulation was applied by way of a MagProX100 machine  using a B65 figure-of-eight-shaped coil oriented tangentially to the scalp in the anterior–posterior direction. This coil was fixed to an arm that could be adjusted in three dimensions. The coil was positioned over the left M1 (primary motor cortex) with an optical neuronavigation device . We chose to target the left M1 over the hand representation as in previous studies ,23. IndeThe resting motor threshold (RMT) was defined as the lowest intensity eliciting a motor evoked potential (MEP) with a peak-to-peak amplitude of at least 50 mV in 50% of trials. MEPs were recorded for the first interosseous muscle of the right hand, with an electromyogram amplifier module  and surface electrodes, as in previous studies ,27.A stimulation session consisted of 15 10-s pulses at 10 Hz, separated by a 50-s interval, for a total of 1500 pulses and applied at 80% of the RMT ,26,27,28This pilot study allowed assessment of the feasibility and safety of rTMS treatment for refractory endometriosis pain, paving the way for a future randomized controlled trial. The sample size estimation was fixed in accordance with Fleming’s multi-stage design, to include one group and multi-stages (between 1 and 5) providing filtering steps leading to a decision type go/no go. In view of capacity and feasibility, two steps were maintained with a lower boundary of 25% (maximum inefficacy) and an upper boundary of 50% (minimum efficacy) as recommended in the literature. Due to the type of design and hypotheses, type I error α and statistical power corresponded respectively to 5% and 80% with the following decision rules: With 12 patients included at the end of the first stage, treatment was considered not feasible if three or more patients reported a pain increase or did not tolerate the five rTMS sessions, and feasible if seven or more responses were observed. In the event of four to six responses being observed, 12 additional patients would be needed to make definitive conclusions with a feasible treatment requiring 10 or more responses.The statistical analysis was performed using Stata software, version 13 . The tests were two-sided, with type I error set at α = 0.05. Continuous data were presented as the mean ± standard deviation or the median [interquartile range] according to statistical distribution . The percentage of patients tolerating five stimulation sessions and showing no pain increase on D8, compared to assessment performed over the previous 4 weeks, was presented with a 95% confidence interval. Paired comparisons were carried out using the Student paired t-test or Wilcoxon test. Effect size for repeated measures is estimated using the difference between two means divided by a standard deviation and taking into account within-patient correlation . Effect The normality of residuals was studied using Shapiro-Wilk’s test. When appropriate, a logarithmic transformation was proposed so as to achieve normality for the dependent outcome.The study was registered (NCT03204682) and received the ethic committee’s approval (Comité de Protection des Personnes Sud-Est 06).Thirteen women with chronic pelvic pain due to endometriosis were included from April 2016 to August 2017. One patient withdrew from the study before the first rTMS session due to fear of possible side effects and another patient included in accordance with the Fleming’s design. Thus, 12 patients completed the study . The meaThe main outcome was achieved with a tolerance rate of 100% (All patients tolerated the five rTMS sessions and none reported a significant pain increase). No serious adverse effects were noted, however, 50% of patients reported experiencing light headaches and 25% described asthenia. p = 0.01; ES = 0.74 ) and in the overall impact of pain on quality of life ). These significant improvements were found to continue until D28 for both intensity ) and interference ) ) . PGIC results on D8 showed that nine patients experienced some improvement  . Four ofp = 0.04; ES = 0.60 ), with a total GIQLI  score of 60.6 ± 14.0 before stimulation and 71.1 ± 13.3 at D8. Continued significant improvement was noted until D28 with a score of 72.4 ± 20.8 ) (p > 0.05). The GIQLI score is made of sub-scores focusing on symptoms, emotions, physical function, and social function. The most important variation was observed for symptoms, the sub-score going from 37.8 ± 8.7at baseline to 44.3 ± 9.4 at day 8 ). The other sub-scores did not present a statistically significant variation. Concerning gastrointestinal quality of life, a significant improvement was observed after treatment ) . This GIp = 0.047; ES = 0.88 ) and unchanged for the mental component ). Assessment by SF-36 at D8 showed that the improvement in Quality of Life was marginally significant for the physical component ) together with a non-significant improvement in pain levels ). There was a significant correlation between pain variation on day 8 and the variation of the emotional part of the EHP30 questionnaire .Following rTMS treatment (D8), several changes in EHP-30 questionnaire sub-scores were noted, notably an improvement in emotional well-being ).At baseline, 91.7% (11/12) of women reported a depressive state according to Beck’s questionnaire results and 50% were alexithymic. STAI at D8 revealed no variation in anxiety compared to pretreatment scores ) and pain interference by 2 points ), with moderate to large effect sizes. PGIC assessment revealed an improvement for a large majority (9/12) of these patients experiencing refractory pain. An improvement was also noted in the physical component of the SF-36 and for gastro-intestinal quality of life parameters.Our study demonstrates a perfect tolerance of five daily 10 Hz rTMS sessions in patients with chronic refractory pelvic pain due to endometriosis. Overall, pain intensity was reduced by 1 point  in this open-label study is low. A recent meta-analysis defined a minimal clinically important difference (MCID) of 10 mm using the VAS for women with pain due to endometriosis . For BPIConcerning quality of life, it has been demonstrated that SF-36 and EHP-30 perform well in the evaluation of endometriosis patients .This study is the first to study rTMS in the management of endometriosis using a protocol proven effective for neuropathic pain and fibromyalgia ,10 and nTo date, high frequency  rTMS over M1 is the only validated protocol for pain treatment ,10,39. AThe main limitations of the present study concern the absence of a control group and the limited sample size. The placebo effect can be important in pain studies, though likely to be limited in patients with chronic pain undergoing rTMS . Using FThis prospective pilot study showed that high frequency motor rTMS is feasible and well-tolerated in patients with refractory chronic pelvic pain due to endometriosis. A majority of these patients reported at least minimal improvement on the PGIC scale after five rTMS sessions. Although pain reduction was modest, the impact on pain interference and gastro-intestinal quality of life was perceived as beneficial for these women. This study paves the way for a future study of analgesic efficacy using a double-blind trial and presents initial promising support for a new analgesic technique for use in daily clinical practice in patients for whom all other treatments have failed. Although non-invasive and well-tolerated, a confirmatory study using a double-blind design is mandatory before developing such treatment in daily practice.


How has opioid use in pediatric patients changed over the past 10 years, and what factors are associated with differences in opioid use?A cross-sectional study of 69 152 emergency department visits found that opioid prescribing rates decreased between 2006 to 2010 (8.23%) and 2011 to 2015 (6.30%). Region, race, age, and payment method were associated with differences in opioid prescribing.Opioid rates have decreased in recent years but inconsistencies in prescribing continue, suggesting the need for further research. This cross-sectional study examines patterns of opioid prescription to US pediatric patients during visits to hospital emergency departments between 2006 and 2015 using data from the National Hospital Ambulatory Medical Care Survey. The use of opioids to treat pain in pediatric patients has been viewed as necessary; however, this practice has raised concerns regarding opioid abuse and the effects of opioid use. To effectively adjust policy regarding opioids in the pediatric population, prescribing patterns must be better understood.To evaluate opioid prescribing patterns in US pediatric patients and factors associated with opioid prescribing.This cross-sectional study used publicly available data from the National Hospital Ambulatory Medical Care Survey from January 1, 2006, to December 31, 2015. Analysis included the use of bivariate and multivariate models to evaluate factors associated with opioid prescribing. Practitioners from emergency departments throughout the United States were surveyed, and data were collected using a representative sample of visits to hospital emergency departments. The study analyzed all emergency department visits included in the National Hospital Ambulatory Medical Care Survey for patients younger than 18 years. All statistical analysis was completed in June of 2018 and updated upon receiving reviewer feedback in October of 2018.Information regarding participants’ medications was collected at time of visit. Participants who reported taking 1 or more opioids were identified.Evaluation of opioid prescribing patterns across demographic factors and pain diagnoses.P = .004). White individuals were prescribed an opioid at 8.11%  of visits vs 5.31%  for nonwhite individuals (P < .001). Those aged 13 to 17 years were significantly more likely to receive opioid prescriptions  than those aged 3 to 12 years  or 0 to 2 years . Patients using Medicaid for payment were less likely to receive an opioid than those using private insurance . There was no significant difference in opioid prescription across sexes. Opioid prescribing rates decreased when comparing 2006 to 2010 with 2011 to 2015 ; however, opioid prescribing rates remained unchanged in specific pain diagnoses, including pelvic and back pain.A total of 69 152 visits with patients younger than 18 years  were included, which were extrapolated by the National Hospital Ambulatory Medical Care Survey to represent 293 528 632 visits nationwide, with opioid use representing 21 276 831 (7.25%) of the extrapolated visits. Factors including geographic region, race, age, and payment method were associated with statistically significant differences in opioid prescribing. The Northeast reported an opioid prescribing rate of 4.69%  vs 8.84%  in the West (This research demonstrated an overall reduction in opioid use among pediatric patients from 2011 to 2015 compared with the previous 5 years; however, there appear to be variations in factors associated with opioid prescribing. The association of location, race, payment method, and pain diagnoses with rates of prescribing of opioids suggests areas of potential quality improvement and further research. In the treatment of moderate and severe acute pediatric pain, it can be difficult to balance the risks of treatment while providing adequate pain control. Health care practitioners often must choose between the use of opioids, traditional nonnarcotic agents , and nonpharmacological options.Acute pain is common among pediatric patients presenting to hospital emergency departments (EDs).2 Although not as extensive as in adults, the use of opioids in pediatric patients had seen a significant increase prior to 2010, with the rate of opioid prescribing doubling from 1994 to 2007 in pediatric patients.3 More specifically, ED prescribing of opioids in pediatric patients increased from occurring in 11.2% of visits in 2001 to 14.5% in 2010.4 Additionally, studies5 suggest that when opioids are prescribed to pediatric patients, approximately 60% of opioid prescriptions dispensed include more opioids than are needed to treat the acute pain disorder.The use of opioids to treat moderate to severe pain in pediatric patients for specific pain disorders has generally been considered appropriate and necessary; however, recent concerns regarding opioid abuse and increases in opioid-related hospitalizations and deaths among pediatric patients have raised questions about the practice of prescribing opioids for management of pain in children.6 have shown that as opioid prescribing has increased in pediatric patients, the rate of opioid abuse and opioid-related death have also increased among these patients. Additionally, in recent years, as opioid prescribing rates have actually declined among pediatric patients, opioid-related hospitalizations have continued to increase.7 This continued trend reinforces the potential risk associated with opioid use in pediatrics, with increased likelihood and accelerated progression from use to abuse in pediatric populations.8 Research has shown that young people who report receiving a legitimate prescription for a narcotic pain medication by 12th grade are significantly more likely to abuse prescription pain medications in the future.10 This risk for misuse has also been shown among pediatric patients who report nonmedical use of opioids prior to adulthood.11 The risks associated with use of opioids at an early age suggest the need for further review of opioid prescribing in pediatric patients.Recent studiesThis study aims to evaluate trends of pediatric opioid prescribing in EDs in US hospitals and patient-related factors associated with opioid prescribing.13 Prior to completion of this study, the Chapman University institutional review board reviewed and granted this study exempt status, as the analysis of deidentified, publicly available data does not constitute human subjects research as defined in federal regulations and as such does not require review. Hence, informed consent was not necessary. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.This study analyzes data collected from the 2006 to 2015 National Hospital Ambulatory Medical Care Survey (NHAMCS) focusing on patients younger than 18 years. This survey is conducted using a representative sample of visits to EDs, collecting data from medical records on patients’ symptoms, diagnoses, comorbidities, demographic characteristics, and medications ordered or provided. The survey uses a complex 4-stage study design. A description of the sampling design is available elsewhere.opioid or other.14 Medications included all drugs reported as either ordered as a prescription or provided during the visit.The NHAMCS data were weighted by the Centers for Disease Control and Prevention (CDC) using the most recent census data to most accurately represent national hospital visit and patient population characteristics. All analyses were conducted on weighted data, as recommended by the CDC’s National Center for Health Statistics, to be representative of national hospital visit characteristics. The use of opioids was determined using the CDC’s New Ambulatory Care Drug Database system, with drugs being classified as International Classification of Diseases, Ninth Revision, Clinical Modification codes. Pain diagnosis codes were established based on the clinical classification software categories available from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization project. Included pain categories were abdominal pain, arthritis or joint pain, back pain, cancer-related pain, chest pain, cholelithiasis, fractures, headache, injury excluding fracture, neck pain, nephrolithiasis, pelvic pain, sickle cell anemia, dental or jaw pain, fibromyalgia, and peripheral neuropathy. Pain categories that did not meet the minimum of 30 visits in the unweighted sample were recategorized into a category labeled other pain.A visit was considered pain related if a pain diagnosis was reported in the reasons for the visit through the evaluation of reported Metropolitan setting of the visit was determined using Metropolitan and Micropolitan Statistical Area methodology, the definition used by federal agencies for research purposes. Length of visit was recoded into dichotomous categories of prolonged (lasting >240 minutes) or not prolonged (lasting ≤240 minutes).svydesign from the R package survey was used to account for stratified, clustered, and weighted variables in the NHAMCS data. A Wald test of association was used to determine significance for all analyses.All participants’ records were stored in a relational database using the open-source database software MySQL version 5.7.11 (Oracle). All statistical analyses were preformed using the open-source statistical computing software R version 3.2.3 (R Foundation) and finalized October 12, 2018. The function Descriptive statistics were used to compare the characteristics of ED visits associated with opioids with those in which patients were not currently prescribed an opioid. Wald tests of association were used to determine significance for bivariate analysis, and logistic regression models were conducted using weighted patient data with opioid use as the dependent variable and age, race, sex, pain diagnosis, payment method, region, and length of ED visit as dependent variables. The model was simultaneously adjusted for all dependent variables.P < .05. All analysis conducted used cohorts of more than 30 visits and had a relative standard error of less than 30% per CDC guidelines. The CDC provided detailed documentation of the NHAMCS instrument, methodology, and data files that were used as the basis for this analysis and are available elsewhere.12All confidence intervals correspond to 95% CIs, as computed from the standard error. Comparison and associations were considered significant if 2-sided P < .001).A total of 69 152 hospital ED visits by patients younger than 18 years at the time of the visit  from January 1, 2006, through December 31, 2015, were included. These visits were extrapolated by the National Hospital Ambulatory Medical Care Survey to represent 293 528 632 hospital ED visits throughout the United States, with 7.25%  of those visits (21 276 831) associated with either being currently prescribed an opioid or attaining one from the visit. Among pediatric patients, those aged 13 to 17 years were significantly more likely to have visits associated with opioid administration and/or prescription, with 16.20%  of individuals aged 13 to 17 years having an opioid prescribed compared with 6.59%  for those aged 3 to 12 years and 1.70%  for those aged 0 to 2 years (P < .001). The likelihood of a visit being related to an opioid prescription was also statistically significant when comparing regions of the country, with visits occurring in the Northeast being associated with the lowest prescribing rate, having an average prescription rate of 4.69%  compared with 8.84%  for the West, the highest-prescribing region (P = .004). Patients using Medicaid for payment were less likely to receive an opioid than those using private insurance . The population density of the area where the individual received care did not appear to be associated with overall prescribing rates of opioids, with similar opioid prescribing rates between metropolitan and nonmetropolitan areas. Further details on cohort size and weighted and unweighted visit counts, as well as opioid prescription rates based on specific demographics throughout the cohorts, are available in Significant differences in opioid prescription rates were observed across varying demographic factors. White participants reported an average opioid prescription rate of 8.11%  vs 5.31%  for nonwhite participants . Patients diagnosed with pain associated with a fracture had the greatest likelihood of being prescribed an opioid, with an aOR of 14.27  when compared with the referent group. Pelvic pain and arthritis or joint–related pain were the next 2 pain diagnoses most likely to result in opioid prescribing, with aORs of 5.12  and 4.84 , respectively. Visits associated with headaches and abdominal pain diagnoses had similar likelihood of opioid use, with aORs of 2.89  and 2.69 , respectively.Logistic regression analysis of payment method and opioid use demonstrated similar opioid prescribing rates among those who reported using private insurance, Medicare, and self-pay. Those using Medicaid as their primary payment method had a significantly lower likelihood of being prescribed an opioid, with an aOR of 0.74  compared with those using private insurance. Comparing opioid prescribing in patients based on race revealed that white patients were more likely to be prescribed an opioid, with an aOR of 1.34  compared with nonwhite patients. There was no difference in opioid prescribing between sexes, with female patients having an aOR of 1.03  compared with male patients.P < .001). Specifically, opioid prescribing rates for headaches, which had an overall prescribing rate of 16.6%, decreased from 21.93%  to 12.51%  (P = .008). The opioid prescribing rates for non–fracture-related injuries, abdominal pain, and non–pain-related visits also decreased over this time  to 6.30%   compared with those aged 3 to 12 years (6.59% of visits) and 0 to 2 years (1.70% of visits). Although the overall rate of opioid prescribing for pediatric patients was lower than for adults, the fact that more than 16% of all visits for those aged 13 to 17 years have an opioid associated with them suggests that overall opioid use is also relatively high in pediatric patients. The rate of opioid prescribing related to headaches in this study was 16.6%, which was significantly lower than the previously reported rate of 46%.Time-lapse analysis does show a reduction in overall opioid use comparing 2006 to 2010 with 2011 to 2015. This reduction suggests that the scrutiny of the safety of opioid use overall and particularly in pediatric patients has resulted in prescribers reevaluating their use of opioids overall. This reduction in use is primarily driven by reductions in opioid use in specific pain diagnoses, including headache, abdominal pain, and non–fracture-related injuries. The overall reductions were also partially the result of reduced opioid use in non–pain-related visits, which decreased from occurring in 4.07% of visits to 3.18%. The lack of change over time in the use of opioids for other pain diagnoses, particularly back and pelvic pain, suggests that alternative treatment options need to be further evaluated or encouraged among health care professionals. The use of opioids in back pain is of significant concern because growing research suggests that chronic use of opioids to treat back pain is not effective for both pain and function and is associated with significant safety concerns.Our findings indicate that patient visits in the western region of the country  are significantly more likely to be prescribed an opioid, while patients visits in the Northeast  are associated with the lowest likelihood of an opioid being prescribed despite a lack of significant difference in pain-related diagnosis in these region. Factors affecting the regional variability in opioid prescribing in pediatric patients need to be further evaluated to better understand what may be driving the overall prescribing patterns in each region, particularly those with higher opioid prescribing rates.20 When holding constant for pain diagnosis, white patients were significantly more likely to receive an opioid. For instance, white patients reporting abdominal pain were almost twice as likely to receive an opioid than their nonwhite counterparts. While there are numerous potential explanations for this difference, further subset analysis is needed to better evaluate the use of opioids based on race to determine the association of pain scale reports, age at time of visit, other patient-specific factors, and prescriber-specific factors with opioid prescribing across racial and ethnic groups.Race additionally had a significant association with overall prescription trends, with white patients having a significantly increased likelihood of being prescribed an opioid compared with nonwhite patients. These findings are similar to previous research that has indicated significant racial differences in prescription patterns of opioids in adult patients.21 This raises questions regarding the biases that may exist in prescribers when treating patients covered by state Medicaid programs, which appears to be true in pediatric patients as well as adults. This study’s analysis found that, unlike previous studies in adults, prescribing rates were similar between sexes.Similar to previous research, individuals whose primary payment method reported was state Medicaid had a lower likelihood of being prescribed an opioid.The relationship between opioid use rates in pediatric patients and pain diagnoses suggests that different pain-related diagnoses are viewed by prescribers as more appropriate than others for opioid use. As expected, pain related to fracture injuries had the highest rate of opioid prescribing, which remained consistent when comparing 2006 to 2010 with 2011 to 2015. The relatively high use of opioids in pelvic pain and back pain, which also lack a statistically significant reduction over time, suggests additional evaluation is necessary regarding prescribers’ attitudes toward treatment options in these specific pain-related diagnoses. Although the percentage of visits for headache, abdominal pain, non–fracture-related injuries, and non–pain-related diagnoses associated with opioid use has decreased, the continued use of opioids suggests additional opportunity for further evaluation and prescriber outreach to ensure appropriate and consistent prescribing of opioids. Each of these pain diagnoses have limited need for the use of opioids, and the reduction of use over time is a positive trend; however, more significant reductions of opioid use in these clinical circumstances would be appropriate.Limitations of this study include its retrospective nature and the general limitations of using a cross-sectional data set. Owing to this limitation, we can only report the findings of the analysis and are not able to draw conclusions about the causative nature of factors associated with opioid prescribing patterns. Additionally, this study is not able to determine which factors may have been associated with a reduction in the use of opioids for specific pain diagnoses. Many factors may need to be further explored to understand their role in opioid prescribing patterns. In addition, a number of comorbidities and preexisting diseases may affect the choice of drug for pain management. For example, opioid therapy is generally the first-line approach for moderate to severe pain control, alone or in combination with other medications, in patients with active cancer, particularly when a patient is neutropenic. The presented study is not able to evaluate patients’ comorbidities or determine their potential effects on opioid prescribing.The findings of this study suggest the overall use of opioids in pediatric patients in EDs has declined since 2010; however, further research is warranted given the remarkable variability in opioid prescribing rates based on patient-specific demographic characteristics and pain-related diagnoses. Although the use of opioids is indicated for specific pain-related visits, it is important to keep prescribing consistent across all health care professionals regardless of patient demographic characteristics. The lack of consistency in prescribing opioids observed in this study also indicates the need to develop a more standardized opioid use guideline in pediatrics, which can help guide prescribers to make informed decisions when considering opioids for the treatment of patients younger than 18 years.