Constipation, one of the adverse effects of opioid therapy with a major impact on quality of life, is still an unmet need for cancer patients, particularly those with an advanced and progressive disease, and for non-cancer patients chronically treated with opioids. The awareness of this condition is poor among healthcare providers, despite the recent publication of guidelines and consensus conferences. An early multidisciplinary approach of opioid-induced bowel dysfunction (OIBD), based on available therapies of proven effectiveness, could support clinicians in managing this condition, thus increasing patients’ adherence to pain therapy. Several Italian experts involved in the management of patients suffering from pain  joined in a Board in order to draw up an expert opinion on OIBD. The most frequent and still unsolved issues in this field were examined, including a more comprehensive definition of OIBD, the benefits of early intervention to prevent its occurrence and the most appropriate use of peripherally acting mu-opioid receptor antagonists (PAMORAs). The use of the recently introduced PAMORA naloxegol was analysed, in light of the current literature. The Board proposed a solution for each open issue in the form of recommendations, integrated with the contribution of representatives from different disciplines and often accompanied by procedural algorithms immediately usable and applicable in daily clinical practice. Safety and quality of life of the patient suffering from pain and from the adverse effects of pain therapies have been the mainstays of this expert opinion, in cooperation with general practitioners and caregivers. The optimal management of opioid therapy–induced adverse effects is still an unmet need. Constipation is a considerable issue for cancer patients, particularly those with a progressive disease . An accuAn early multidisciplinary approach may support clinicians in the management of opioid-induced constipation (OIC), minimise the risks of neglecting it and increase the adherence of patients to the proposed pain therapy.A panel of Italian clinicians from different areas of expertise  convened to draw up an expert opinion on OIC, aiming at constituting a first step towards a shared pathway among the various clinical disciplines and hopefully to involve nursing professionals and caregivers.Palliative care networks show different organisational models, generally developed on the experience of each group. Such fragmentation may affect care, raising the risk of inadequate treatment. The management of constipation requires an interdisciplinary approach, especially in palliative care patients. For patients with advanced disease, the most common causes of constipation are reduced physical activity, being bedridden, dehydration, loss of autonomy in bowel evacuation, malnutrition and indeed the use of opioids.reduced bowel movement frequency;development or worsening of straining to pass bowel movements;a sense of incomplete rectal evacuation;harder stool consistency.The definition of OIC is currently based on four parameters :reduced The term opioid-induced bowel dysfunction (OIBD) is preferred over OIC as it implies a broader definition involving the entire gastrointestinal apparatus and refers to a wider range of parameters, including pain, fatigue, stress, flatulence and duration of constipation  .OIBD is often poorly detected or underestimated and, as a consequence, addressed later in comparison to other adverse effects of opioid therapy. In clinical practice, the available guidelines are not always adequately considered and are sometimes incorrectly applied .The distorted understanding of drug-induced constipation symptoms often leads to the administration of high amounts of bran, resulting in the formation of faecalomas. Elderly and bedridden patients are still treated with Vaseline oil which, in the presence of impaired swallowing, could cause tracheal aspiration and severe pulmonary reactions. More suitable approaches include the administration of osmotics for faecal softening, eventually followed on the third day by stimulants or enemas. The aim should always be the prevention of rectal faecalomas and the subsequent adverse effects, such as agitation, anal spasms, overflow incontinence and occasionally severe ulcerations . The benThe interpretation of guidelines by clinicians is partly misguided by their difficulty in understanding the subjective and objective nature of constipation: as a consequence, its diagnostic framework is still undefined.position paper published in 2016 by the Nordic Working Group, explicitly advises the use of fibre [A of fibre . The posof fibre . The 201of fibre .A relevant factor is the scarce awareness of symptoms by the patients, mostly concerned about pain and their illness. Particularly in home palliative care, nurses play an important role through education, assessment of symptoms and identification of appropriate treatment.The report about bowel function in medical records is normally scarce. For opioid-naïve patients, a diary reporting the frequency of bowel movements, stool consistency and the use of laxatives, before and after the prescription of opioid therapy, is advisable. This would allow the clinician to identify differences between the pre- and post-prescriptive phases and formulate a definitive diagnosis of OIBD.An abdominal X-ray might be helpful in selected cases when physical examination is inconclusive, but it should be recognised that it is often uneasy to perform for patients involved in palliative care programmes, particularly in the home setting.ease of defecation;feeling of incomplete bowel evacuation;personal judgement of constipation.Equally important is to measure the efficacy of treatment and the need for possible changes. Despite the availability of validated measurement scales, these are rarely adopted in clinical practice and limited to clinic research . An examfrequency of bowel movements. Although three bowel movements per week are the optimal frequency , a bowelrectal tenesmus, often described by the patient as a painful spasm, accompanied by an unsuccessful urge to defecate which, if not detected, could lead the clinician to increase the opioid dosage, further worsening the constipation. Importantly, rectal tenesmus must not be confused with the feeling of incomplete bowel evacuation.The BFI can be considered a valid tool for the patient’s subjective evaluation of OIBD. However, also the following should always be monitored and recorded:To integrate the BFI with other items, a revalidation process is needed, which will require a rigorous scientific approach.Other parameters useful to address OIBD are the consistency and form of faeces, evaluated using the Bristol scale and the Rome criteria . A patieEssentially, quick and replicable tools are needed, easily understood by patients and caregivers, to allow the assessment of the baseline condition and adequate ongoing clinical monitoring.The most recent guidelines include indications often unfeasible for fragile patients in a palliative care setting, such as increased physical activity or specific dietary regimes . EnsurinNevertheless, specific recommendations for the management of constipation in palliative care setting have been made .The issue of OIBD cannot be solely associated with the underlying disease, since opioids are used by a wide variety of patients, not only for cancer pain treatment. It is understandable that its psychophysical impact is greater in cancer patients, especially in those receiving palliative care, but the condition of patients under chronic opioid therapy for musculoskeletal pain or neuralgias should not be ignored.The onset rate of OIBD ranges between 2 and 40% , 15, sugOIBD therapy includes several lines of treatment, defined in the most recent recommendations and guidelines , 16.The main characteristic of OIBD is a delayed colonic transit. Opiates interfere with the release of acetylcholine at the level of inhibitory neurons of the myenteric plexus, resulting in an increase in the circular muscle cells tone. The measurement of opioid potency relative to morphine is based on this model of inhibition .This consideration suggests that the prescription of opioid therapy should be associated from the outset with prevention of constipation and close monitoring of therapeutic efficacy every 3 days, at least in the initial phase of treatment. However, pre-existing conditions must be always considered.A key issue is preventing faecaloma. An increased intake of fibre may not be able to stimulate motor activity and paradoxically would favour the formation of faecalomas. Osmotic laxatives are often considered as the first choice to soften faeces, but they are associated with several side effects including flatulence and nausea. Saline laxatives may trigger electrolytic disorders, and disaccharides can cause abdominal distension and flatulence .Among osmotic laxatives, macrogol can be definitely recommended as a preventive therapy, as it is not associated with relevant side effects, except inappetence and nausea when administered at high dosages .macrogol;macrogol plus a stimulant laxative (senna or bisacodyl);association of three or more laxatives in case of non-responsiveness.An algorithm proposed in 2005 suggested [4) receptor agonist stimulating the peristaltic reflex [As a preventive treatment, administration of macrogol should start from 8.75 g of polyethylene glycol (PEG) 4000 combined with electrolytes, dissolved in 125 ml of water (or corresponding dose/volume of other macrogol compound) once a day in patients without constipation, up to a maximum dose of 17.5 g dissolved in 250 ml twice daily. The higher dosages could cause undesirable effects, such as loss of appetite due to fullness and nausea. In such cases, the dose of macrogol should be halved or other drugs should be considered. The response to macrogol generally lasts 5–6 days at the most; for this reason, administration should be started early. In case of unsatisfactory response, a prokinetic agent is suggested. Metoclopramide should be avoided due to its action on the proximal gastrointestinal tract and its side effects . Prucaloc reflex . PrincipLubiprostone and linaclotide exert a secretagogue action, promoting intestinal motility and facilitating bowel transit. Potential side effects are watery diarrhoea, dehydration and electrolyte imbalance .Physical activity, within the limits of the patient’s functional reserve, and hydration are also of paramount importance in the prevention of OIBD.The dose-dependent effect of opioids on bowel transit is a discussed topic , 25. TheIt is widely accepted that the use of two or more laxatives combining a softening and a stimulating action may cause unpleasant side effects, from abdominal pain and flatulence to nausea and vomiting. Consequently, patients may require switching to two or more laxatives or the administration of other drugs against such effects, further worsening their condition.If preventive treatments have proven to be ineffective, opioids should be rotated and, if no favourable results are achieved, a specific pharmacological therapy should be initiated. The drugs should be characterised by rapid onset of action, manageability and ease of use by the patient . BecauseAn objective criterion should be established to determine when to initiate the pharmacological administration of PAMORAs. A timely start would not harm the patient and would be consistent with the terminological use of the OIBD acronym. This approach deviates from the current indications .The pivotal trials of naloxegol showed that the response rate achieved with naloxegol 25 mg was 14–15% higher compared to placebo, whereas in the subpopulation with inadequate laxative response (LIR), the response rate difference between naloxegol 25 mg and placebo exceeded 20% and the number of patients to be treated due to non-response was halved , 29.Macrogol (125 ml) in the preventive phase, with reassessment every 3 days;at the onset of constipation, macrogol at incremental doses (125 ml twice daily up to 250 ml twice daily), with assessment every 3 days, for 1 week;in case of no response after 1 week, at the maximum dosage of macrogol, the concurrent administration of stimulants, such as bisacodyl 10 mg/day  or sennaafter a further week, in case of no response and after an enema rescue therapy, start PAMORA therapy.Therefore, a possible algorithm is shown:If a patient is constipated and had not preventively received macrogol, it should be prescribed at the maximum dosage along with opioid rotation .Based on the previously reported timeframe, from the onset of constipation, 14 days of intervention with macrogol and stimulants should occur before starting with the PAMORA agent.a 14-day waiting time for outpatients and patients receiving early palliative care;a 7-day waiting time for terminally ill patients, with limited life expectancy.For advanced cancer patients and terminally ill, a timeframe of 2 weeks could be excessively long. Two distinct scenarios should be outlined before pharmacological treatment with PAMORAs:In patients with an extremely limited life expectancy and in case of inefficacy of laxatives, the maximum waiting time should not exceed 2–3 days.The early use of PAMORAs should be considered as a strategy for reduced social care costs of OIBD.In two pivotal trials in which patients were receiving oral morphine, two doses of naloxegol, 25 mg and 12.5 mg, were compared , 33. EffRisks related to naloxegol therapy include diarrhoea and abdominal pain. In the KODIAC-08 study at 52 weeks, the incidence of abdominal pain was higher among patients treated with naloxegol 25 mg compared to those administered usual therapy (17.8% vs. 3.3%); pain intensity, however, was not specified . Only 9 Patients on naloxegol therapy should be contacted every 3 days during the initial stage of treatment to evaluate drug efficacy and side effects. Administering the drug every 2 days if abdominal pain occurs is not advisable; the only possible solution is a dose reduction or discontinuation of therapy  and to cAnother frequent event to be monitored is the patient’s self-interruption of medication once evacuation has occurred. This phenomenon has been reported in 80% of the cases of non-efficacy or reduced efficacy .When should the therapeutic response to naloxegol be considered satisfactory? A clinician should not necessarily aim for a complete resolution of constipation, as well as to meet the challenging target of total pain relief following the intake of strong analgesics. Guidelines suggest that patient’s personal opinion should be considered when assessing the benefits of the therapies.One evacuation every 3 days with soft and not separate hard lumps should be considered an acceptable therapeutic objective. Failing to evacuate on a daily basis could cause patients to experience abdominal bloating and to autonomously take laxatives. When taking naloxegol, laxatives should be discontinued. In the event of abdominal bloating, the administration of absorbents such as silicone or charcoal is advisable. Probiotics may be prescribed in case of mild to moderate abdominal bloating . FinallyBesides diarrhoea, abdominal pain and flatulence, headache and nausea are two other adverse events associated with naloxegol therapy . HeadachIn palliative care settings, the patient’s subjective judgement of the negative impact of constipation on quality of life is a key element that must guide clinicians in selecting therapy. Often, the more the evacuation frequency resembles that preceding the onset of the disease, the greater the patient’s satisfaction. In patients at an advanced stage of disease, the simplest preventive strategy against abdominal tension caused by therapies is the administration of probiotics, while absorbents could affect the absorption of other drugs, making the therapeutic management of the patient more complex.responder (evacuating three times per week);ultra-responder (evacuation frequency higher than three spontaneous bowel movements per week);non-responder (evacuation frequency less than two spontaneous bowel movements per week). If difficult evacuation persists, reducing the naloxegol dose is not recommended.Definitely, a bowel movement every 3 days would be an acceptable goal, provided that the patient’s quality of life is subjectively satisfactory. Patients can be grouped into three types:In the absence of a response, it is advisable to give macrogol at the maximum recommended dose (250 ml twice daily) and, on the third day without evacuation, administer a stimulant (bisacodyl or senna).If a patient is a responder, naloxegol can be continued for as long as the patient is receiving opioids. To date, available data on the use of naloxegol do not extend beyond 52 weeks .Patients responding to naloxegol in the short term: dose maintained and interruption of the treatment contraindicated. No tolerance of mu receptors has been observed at enteric level . It is aPatients responding to naloxegol in the short term and on a regimen of opioid rotation: consider a reduction of the dose and monitoring.Patients responding to naloxegol in the short term and suffering from abdominal pain and bloating: consider a reduction of the dose and monitoring.Patients not responding or not adequately responding to naloxegol in the short term: not advisable a dosage increase from 25 to 50 mg/day, as it would result in an increase in adverse effects, without leading to further improvement in efficacy .The Board agree on the definition of four clinical scenarios:The Board unanimously agree that the naloxegol dose of 25 mg/day should be maintained, even if the patient reports an evacuation frequency higher than three bowel movements per week. A time-limited discontinuation could provide an indication of therapeutic efficacy in a responsive or ultra-responsive patient.The occurrence of a rebound effect in the cases of naloxegol discontinuation should be ascertained; unfortunately, such investigations are lacking.It has been observed that for hospice patients with the low Karnofsky index, bedridden or receiving parenteral nutrition, the response to naloxegol is lower than for more active patients with a higher performance status .The naloxegol dose de-escalation could be considered in the event of adverse effects or based on patient preference and during opioid switching. In contrast, naloxegol discontinuation should be considered when opioid therapy is discontinued, even in the case of persisting constipation. Particularly for non-cancer pain, if constipation persists after discontinuation of opioids and naloxegol, another cause must be sought.in subjects with OIBD where opioids are administered for cancer pain, the duration of therapy with naloxegol should consider the prognosis of the disease. In responsive patients with a reasonable prognosis but with swallowing difficulties, the drug can be administered as a crushed tablet mixed in water and given orally or even via a nasogastric tube if already inserted for other therapeutic purposes.in subjects with OIBD where opioids are given for non-cancer pain, attempts to reduce and/or discontinue the opioid should be associated with periods of PAMORA discontinuation.Indeed, two different scenarios can be defined:Alongside naloxegol therapy, a patient with OIBD should have already undergone opioid switching. The selection of the opioid is based on the clinician’s judgement and not on therapeutic protocols, which have never been definitely established . Early oThe Board highlight the feasibility of using naloxegol in case of opioid switching to oxycodone plus naloxone , or in case the patient experiences OIBD while already under this opioid. The association of naloxegol with oxycodone plus naloxone is generally not contraindicated . An incrin case of oxycodone plus naloxone, naloxegol should be discontinued or not prescribed;in case of a switch from oxycodone plus naloxone to only oxycodone, naloxegol should be associated if OIBD occurs.In summary:studies on the duration of naloxegol therapy and on the effects of its discontinuation;studies on the efficacy of naloxegol after a dose reduction to 12.5 mg/day;studies on the association of naloxegol with laxatives in non-responsive patients, as suggested by the EFIC Scandinavian guidelines ;pharmacoeconomics studies to assess the cost-benefit ratio associated with the strategy of anticipating the drug treatment with PAMORAs.OIBD is an important and common problem in the context of pain medicine and palliative care. The treatment of OIBD should be managed by a multidisciplinary team, and it is advisable to involve general practitioners, because patients on opioid therapy very often receive both hospital and home care. Anyway, the awareness and perception of this problem is still poor among health providers, despite the publication in recent years of guidelines and consensus conferences. We are aware that all the statements included in this text are expression of the opinions and personal experiences of a multidisciplinary Italian Board, which was constituted with the aim to offer a pragmatic and feasible approach to a heavy problem that affects many suffering and frail patients. Clinical research and practice jointly advance towards optimising the care of painful patients treated with opioids. PAMORAs are a valid and scientifically supported therapeutic aid for the treatment of OIBD. Among them, naloxegol is a promising drug, for which an increasingly widespread use is expected. The following would be desirable:


Opioid overdose is a major public health problem. Emergency physicians need information to better assess a patient’s risk for overdose or opioid-related harms. The purpose of this study was to determine if patient-reported preference for specific pain medications was associated with a history of lifetime overdose among patients seeking care in the emergency department (ED).ED patients (18–60 years) completed a screening survey that included questions on overdose history, ED utilization, opioid misuse behaviors as measured by the Current Opioid Misuse Measure (COMM), and analgesic medication preferences for previous ED visits for pain with specific responses for preference for hydromorphone (Dilaudid®), morphine, ketorolac (Toradol®), “no preference” or “never visited the ED for pain.” We compared individuals who reported a lifetime history of overdose descriptively to those without a lifetime history of overdose. Logistic regression was used to determine factors associated with a history of overdose.We included 2,233 adults in the analysis (71.5% response rate of patients approached) with 532 reporting at least one lifetime overdose. In the univariate analysis, medication preference was significantly associated with overdose history (p < .001); more patients in the overdose group reported preferring morphine and hydromorphone and those without a history of overdose were more likely to have no preference or say they had never visited the ED for pain. In the logistic regression analysis, patients with higher odds of overdose included those of Caucasian race, participants with a higher COMM score, preference for ketorolac, morphine or hydromorphone. Those who were younger, female and reported never having visited the ED for pain had lower odds of reporting a lifetime overdose. Having “any preference” corresponded to 48% higher odds of lifetime overdose.Patients with a pain medication preference have higher odds of having a lifetime overdose compared to patients without a specific pain medication preference, even after accounting for level of opioid misuse. This patient-reported preference could cue emergency physicians to identifying high-risk patients for overdose and other substance-related harms. Overdose is a serious public health problem in the United States, where the rate of opioid-related deaths has increased 200% since 2000. Emergency medicine providers are often charged with seeing patients with acute pain or acute exacerbations of chronic pain under hectic conditions without the benefit of an existing relationship or extensive information on the patient’s background. While there are many different self-report screening tools to understand individual patient risk for opioid-related harms when prescribing opioids, these tools are not routinely used in the ED. Many of these tools were developed specifically for patients initiating chronic opioids such as the Opioid Risk Tool, There has recently been much effort devoted to understanding patient-related risk factors associated with opioid-related harms including overdose. Patients on high daily opioid doses, concurrent use of sedative medications such as benzodiazepines, substance-use comorbidity, or patients who are prescribed extended-release or long-acting opioids are at increased risk for having an overdose. 17What do we already know about this issue?Overdose is a major public healthissue and emergency physicians don’t have good validated tools to assess risk for previous overdose.What was the research question?Is self-reported preference for pain medication during an emergency department (ED) visit associated with a previous overdose.What was the major finding of the study?ED patients with a self-reportpreference for any pain medication have increased odds of previous overdose.How does this improve population health?Patient-reported preference forpain medication should be explored further and could cue emergency physicians to identifying high-risk patients.Information provided directly by patients could be a rapid and easy way to obtain useful information to supplement other tools such as the EMR or PDMP to understand opioid-related risks. Patients presenting for pain-related ED complaints may provide information regarding their preference for certain pain medications. Asking for a specific medication by name is one of the aberrant drug-related behaviors noted by pain medicine expertsThe objective of this study was to determine whether self-reported preference for pain medication during a visit to the ED was associated with a previous overdose among patients using the ED for care. We hypothesized that the odds of having a previous overdose will increase respectively as patients prefer hydromorphone (Dilaudid®), morphine, or ketorolac (Toradol®)compared to patients with no preference for a certain pain medication.We conducted a secondary analysis of cross-sectional screening data obtained as part of the screening and recruitment phase of the Safety and Prevention Outcomes Study (SPOS), an ED-based, brief intervention aimed at reducing opioid overdose behavior in at-risk patients.20We recruited participants from the University of Michigan Health System ED, a Level I trauma center located in Washtenaw County, MI, with a census of 85,000 adults annually. Participants were recruited Monday through Friday and two weekends per month between the hours of 6:30 am and 1:59 pm, from April 2013 to March 2014. Two trained research assistants (RAs) identified patients 18–60 years old without regard for chief complaint using computerized tracking logs, and they approached those placed in private treatment rooms. At the beginning of the shift, RAs would be randomly assigned areas of the ED to start recruitment and approach all potentially eligible patients in that zone who weren’t receiving medical care or talking with medical staff. Patients were excluded from screening if they did not understand English; were in police or corrections custody; had cognitive or other impairment precluding ability to consent ; were medically unstable requiring immediate resuscitation , or were presenting for evaluation and treatment of sexual assault or suicidal ideation.RAs obtained written informed consent and facilitated a brief, self-report screening survey using a tablet computer or pen-and-paper survey (when computers were unavailable), for which participants received a $1.00 gift. Participants were given the option to complete the screening independently using the tablet computer or by having the RA read the questions and input the answers . During the consent process, we told possible participants we would be gathering information on physical and mental health and substance-use behaviors and depending on their answers they might be eligible for the next part. Participants who completed the screening did not know the intervention was to prevent overdose-risk behaviors. See taking too much drugs or medications/pills and/or drinking too much alcohol,” i.e., “‘poisoning,’ ‘passing out,’ ‘nodding off,’ ‘blacking out,’ or an ‘overdose’ or ‘OD.’” We designed this question to err on the side of high sensitivity, as we hypothesized that many patients in the ED would not identify these serious or life-threatening experiences with the term “overdose.” Lifetime overdose was determined by the answer to the question, “How many times in your life has this kind of situation happened to you?” Any answer other than “never” was coded as positive.The primary outcome measure was lifetime overdose, where overdose was defined as “Age, gender, race/ethnicity, employment status, annual income, and years of education were determined by self-report. Race/ethnicity categories included African-American, White, Hispanic/Latino, Asian, American Indian, and other, and were not mutually exclusive. Annual income was collapsed into four categories , and employment was dichotomized as employed (full-time or part-time) or not employed (unemployed or retired). Years of education was categorized into three groups .drinking too much alcohol,” “taking too many medications,” or “taking too many substances” (each reported as yes/no), and whether they had used opioid analgesics within the six-hour period prior to the current ED visit.ED utilization was determined by the self-reported number of ED or urgent care visits in the prior 12 months (including the baseline visit), and measured as 1, 2–3, 4–6, 7–9, 10–20, and ≥ 21. For this analysis, these scores were dichotomized as < 4 or ≥ 4. This cut-off was chosen to be consistent with previous definitions of “frequent utilizers” in the literature.When you visit the ER, what type of pain medication usually helps relieve your pain best?” Patients were asked to choose among the following: hydromorphone, morphine, ketorolac, “no preference,” “I don’t know,” or “never visited ER for pain.” Patients who had no preference or reported “I don’t know” were combined into one category. We also included the level of non-medical use of prescription opioids (or “opioid misuse”) in the prior three months as measured by the sum of eight items  from the Current Opioid Misuse Measure (COMM). At the beginning of the COMM questions, participants were reminded that ‘Pain medications also called “opioids” include Vicodin, codeine, Oxycontin, morphine, oxycodone, hydrocodone, methadone, hydromorphine, meperidine, fentanyl, or Norco, among others’ and then were able to provide answers to the eight COMM questions, which is a validated tool for assessing opioid misuse behaviors.The key independent variable of interest was patient preference for analgesic medication, which was assessed by asking in the survey, “R version 3.2.3 (R Core Team). We first calculated descriptive statistics among the total sample and among both those that did, and did not, have the outcome variable (lifetime history of overdose). We excluded from the sample participants with incomplete data for the outcome variable or the key independent variable of “analgesic preference.” Between-group comparisons of the distributions of each independent variable (e.g. univariate comparisons) were made using Kruskal-Wallis tests for quantitative variables and χ2 tests for categorical variables, respectively.All analyses were performed using p-values are biased low, and parameter estimates are biased high).For adjusted comparisons, we used logistic regression. Variables included in the logistic model were selected based on clinical and theoretical considerations required to get properly adjusted estimates of the effect of patient analgesic preference. We preferred this approach to a stepwise selection procedure because such methods are known to produce anti-conservative inference  and more likely to report being Caucasian (p<0.001) compared to participants who did not report a lifetime overdose; gender was not significant. (p<0.01). With regard to ED utilization, participants in the lifetime overdose group were more likely to have visited the ED at least four times in the prior year compared to those without a history of lifetime overdose (p < 0.001), and participants with a previous overdose were also more likely to report their current ED visit as related to too much alcohol or drugs (p < 0.001) and noted more pain medications and/or opioids within six hours of the ED visit (p<0.05); although overall frequency of these variables was low. Participants in the lifetime overdose group reported a mean COMM score of 2.6 (standard deviation [SD] 5.4) compared to those without a lifetime history of overdose, who reported a mean COMM score of 0.9 (SD 2.5) (p>0.001), indicating a higher level of current opioid misuse or nonmedical prescription opioid use among participants with a lifetime overdose. Likewise, more patients with a previous lifetime overdose had taken opioids  in the prior three months compared to those without a lifetime overdose (p <0.01). Overall, medication preference for acute pain varied across the two groups, with more participants in the lifetime overdose reporting preference for morphine  and hydromorphone  compared to those in the group without a history of lifetime overdose. There was no difference in the univariate analysis between groups for preference of ketorolac. Those without a lifetime overdose were more likely to report having never visited the ED for pain (p<0.001) or having no preference or an unknown preference (p<0.001) compared to those with a lifetime overdose .Nearly one-third of the sample  reported a history of a lifetime overdose. Among those with overdose, the average number of previous overdoses was 3.1 (SD 1.91). In the logistic regression model evaluating factors associated with a lifetime overdose each analgesic medication  was first included as a separate variable to understand how specific medication preferences were associated with a history of lifetime overdose . In thisTo understand the association of lifetime overdose with any pain medication preference, we performed a second logistic regression model predicting lifetime overdose but with the medication-preference variables  combined into one category to understand if “any preference” provided similar results. Interestingly, “any medication preference” had increased odds of lifetime overdose  suggesting that preference for any pain medication is associated with a history of overdose ; the OR Preference for pain medication type has not been examined previously as a predictor of lifetime overdose. In this investigation, patients’ specific preference for hydromorphone, morphine and ketorolac were all associated with a history of previous overdose after accounting for patient characteristics, including level of opioid misuse with ORs suggesting a modest but significant association. The overall conclusions did not change when ketorolac, morphine and hydromorphone preferences were combined, suggesting that any specific preference for pain medication is associated with a lifetime history of overdose.Previous research has shown that patients who get opioids from the ED are at risk for opioid-related problems and those who misuse prescription opioids have elevated rates of ED utilization. Specifically, adolescent patients who receive parenteral opioids in the ED are more likely to report non-medical use of prescription opioids,Recent studies have shown that previous overdose history is an important predictor of future overdose risk.Using patient-reported preference for a specific pain medication as a marker or tool to identify elevated risk for previous overdose could allow for further targeted screening of patients at elevated risk for future opioid-related harms. These results suggest that information about analgesic preference that is commonly volunteered by patients during an ED visit for pain may have utility in informing an assessment and could be a way to identify patients who would benefit from additional screening or intervention to prevent misuse and/or overdose.Previous investigators have shown that it is feasible to administer a self-report screening tool for opioid misuse at the time of discharge from the ED, which could help guide opioid prescribing.Interestingly, patients who had never been to the ED with a pain-related complaint had decreased odds of having a lifetime overdose. This is consistent with prior literature, which notes that patients on chronic opioid therapy have increased use of healthcare services including the ED.While this study provides novel information around correlations of previous overdose for patients currently in the ED, there are some important limitations to note. This is a cross-sectional analysis that supports an association between lifetime overdose and self-reported preference for pain medication but does not support a causal conclusion. Clinical characteristics including the reason for ED presentation was not obtained, although the screening strategy was broad and systematic. Patients were recruited during day-shift hours and we did not collect data during evenings or nights. Future studies should account for possible differences in patient presentation during evenings and overnight hours.Consistent with all other self-report opioid-misuse measures, the COMM has not been validated in ED settings. The definition of overdose was intentionally broad. While this could be viewed as limiting generalizability, it also likely captures a wide range of overdose behaviors that wouldn’t be captured by a definition that was narrower in scope. The SPOS study occurred at a single institution and thus may not be generalizable to other settings such as rural EDs or to patients with different sociodemographic characteristics. Many measures were obtained through self-report including the main outcome of lifetime overdose. The survey question that provided the main exposure of interest (patient preference) was not cognitively tested with a similar population prior to this study.ED patients with a preference for a specific pain medication have higher odds of having a lifetime overdose compared to patients without a specific pain-medication preference, above the association-attributed current opioid misuse. To our knowledge, this is the first such study to examine and find this association. Further study is needed to determine if patient preference for specific pain medication would lead to a prospective risk of overdose or other opioid-related problems. Emergency medicine providers should be cued to this patient-reported preference, which could assist in further understanding risk for overdose and other opioid-related harms.


Introduction: Abuse of nitrous oxide (N2O) has an unusually high lifetime prevalence in developed countries and represents a serious concern worldwide. Myeloneuropathy following the inhalant abuse is commonly attributed to the disturbance of vitamin B12 metabolism, with severe motor deficits are often noted. The present study aims to elucidate its underlying pathophysiology.Methods: Eighteen patients with N2O abuse or vitamin B12 deficiency were recruited. Comprehensive central and peripheral neuro-diagnostic tests were performed, including whole spine MRI, and thermal quantitative sensory testing (QST). Specifically, paired motor and sensory nerve excitability tests were performed in order to obtain a complete picture of the sensorimotor axonal damage.Results: The mean duration of N2O exposure for the N2O abuse patients was 17.13 ± 7.23 months. MRI revealed T2 hyperintensity in 87.5% of the N2O abuse patients and 50% of the vitamin B12 deficiency patients. In N2O abuse patients, the motor nerve excitability test showed decreased in peak response , increased latency , increased superexcitability , and decreased accommodation to depolarizing current ; the sensory test showed only decreased peak response . Meanwhile, motor test in vitamin B12 deficiency patients showed only decreased accommodation to depolarizing current ; the sensory test showed decreased peak response  increased superexcitability , increased subexcitability , and decreased accommodation to depolarizing current .Conclusion: Compared to vitamin B12 deficiency, N2O abuse patients showed prominent motor superexcitability changes and less prominent sensory superexcitability changes, hinting a unique pathological process different from that of vitamin B12 deficiency. N2O abuse might cause axonal dysfunction not only by blocking methionine metabolism but also by toxicity affecting the paranodal region. All patients received whole spine MRI, except one vitamin B12 deficiency patient.A total of 18 patients with either N2O abuse patients had multiple exposures to N2O inhalation (n = 6) and HC2 with a mean age of 62.11 ± 7.51 years (n = 33). HC1 was age-matched to the N2O abuse patients, and HC2 was age-matched to the vitamin B12 deficiency patients.All Nhalation . On the halation , 16–18. This study was carried out in accordance with the recommendations of the Joint Institutional Review Board of Taipei Medical University. The protocol was approved by the Joint Institutional Review Board of Taipei Medical University. All subjects gave written informed consent in accordance with the Declaration of Helsinki.The Medical Research Council (MRC) strength score combined for 12 specified muscle groups   and NeurNerve excitability studies were performed by stimulating the nerve median at the wrist according to previously described protocols, with skin temperature over the wrist maintained at a minimum of 32.0°C , 15. PaiThe nerve excitability protocol incorporated the following recordings: (1) a stimulus-response (SR) curve; (2) strength-duration (SD) relationship, which determined strength-duration time constant (SDTC); (3) threshold electrotonus (TE) utilizing subthreshold 100-ms polarizing currents in both depolarizing  and hyperpolarizing  directions to change the potential difference across the internodal membrane; and (4) recovery cycle (RC) using a paired-pulse paradigm with a supramaximal conditioning stimulus followed by a test stimulus at interstimulus intervals from 2 to 200 ms. Superexcitability was measured as the maximal threshold reduction and subexcitability as the maximal threshold increase after an interstimulus interval of 10 ms.2O abuse patients, vitamin B12 deficiency patients, and healthy controls were analyzed by using unpaired T-tests or Mann-Whitney U-tests, depending on normality. Equality of variances was calculated with Levene's test. Correlation studies were performed with Pearson's R. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) for Windows version 21  or QTRAC software. All data are presented as the mean ± standard error of the mean. P-values were considered significant if ≤ 0.05.Nerve excitability recording data of N2O abuse patients (n = 8) and vitamin B12 deficiency patients (n = 6). Two patients were excluded due to comorbid diabetes, and two for carpal tunnel syndrome  and vitamin B12 deficiency group (51.68 ± 25.52 pg/ml).The vitamin B12 level was 236.33 ± 52.80 pg/ml in the vitamin B12 deficiency group and 111.50 ± 15.46 pg/ml in the N2O abuse group than in the vitamin B12 group, both in the upper (37.50 vs. 0.00%) and lower (75.00 vs. 33.33%) limbs. While sensory abnormalities are more prevalent in N2O abuse group than in the vitamin B12 group in the upper limbs, the prevalence of sensory abnormalities of both conditions are similar in the lower limbs.A summary of the patients' neurological signs and symptoms are shown in 2O abuse patients , and in 50% of the vitamin B12 deficiency patients . 2O abuse. Furthermore, 2O abuse patients, on one of the patients in the nitrous oxide abuse group.The whole spine MRI revealed T2 hyperintense lesions in the posterior columns in 87.5% of the N2O abuse and vitamin B12 deficiency patients. Thermal QST in the upper limb  and lower limb  confirmed abnormal temperature sensation in the patients.NCS revealed motor and sensory slowing in conduction velocity in both N2O abuse and vitamin B12 deficiency patients.A comparison of the motor and sensory nerve excitability parameters between groups are shown in 2O abuse showed a trend of decreased peak response , increased latency , increased superexcitability , and decreased TE accommodation to depolarizing current [TEd [40–60 ms] 56.53 ± 0.70%, p < 0.05].Compared to those of HC, the motor nerve excitability of the patients with Np < 0.01) and decreased TE accommodation toward depolarization in TEd (40–60 ms) .On the other hand, the motor nerve excitability test of vitamin B12 deficiency patients showed only increased stimulus for 50% CMAP  and decreased peak response .The sensory nerve excitability test of the patients with Np < 0.05) and decreased peak response . Moreover, it revealed additional evidence of sensory axonal dysfunction including decreased SDTC , increased superexcitability , decreased subexcitability , and decreased TE accommodation toward depolarizing current .Sensory nerve excitability test of the vitamin B12 deficiency patients also showed increased stimulus for 50% SNAP  and sensory  axon in N2O abuse patients, as well as for sensory axon in vitamin B12 deficiency patients , suggested that decrease in peak response observed in the present study might be related to axonal loss instead of temporal dispersion.Correlational study between peak response and latency for motor  for motor and TEd (peak)  for sensory axons.In order to clarify the cumulative effect of prolonged intermittent exposure of NR = −0.81, p < 0.05) and sensory rheobase  of vitamin B12 deficiency patients. Interestingly, MRC strength score of tested muscle is correlated with TEh(overshoot)  in motor axonal study of N2O abuse patients.Also, vitamin B12 level was correlated with stimulus for 50% SNAP response , superexcitability . Upper limb cold threshold Z-score was correlated with superexcitability  and latency . Lower limb warm threshold Z-score was correlated with subexcitability .In the sensory axonal study of NZ-score was correlated with peak response  and TEd (40–60 ms) . Lower limb warm threshold Z-score was correlated with refractoriness at 2.5 ms . Lower limb cold threshold Z-score was correlated with peak response , TEd (10–20 ms) , TEd (40–60ms) , and TEd (peak) .Also, in the sensory axonal study of vitamin B12 deficiency patients, the present study found that upper limb cold threshold 2O abuse and vitamin B12 deficiency patients. Nevertheless, the pattern of myeloneuropathy appears to be different between the two groups  receptors  are correlated with MRC strength score of tested muscle in N2O abuse, suggested that nerve excitability parameters may have the potential to monitor axonal damages caused by N2O exposure, and may further add to the value of the nerve excitability test as an evaluation tool for the myeloneuropathy. Correlation between vitamin B12 level with numerous sensory axonal study parameters suggested that the parameters reflect axonal dysfunction related to vitamin B12 deficiency. Correlational study results also showed that RC and TE parameters are correlated with sensory perception threshold in the patients, but the interpretation of the results should be very careful, as the nerve excitability test was not specifically designed to evaluate small fiber function.The fact that motor subexcitability and sensory TEd (peak) are correlated with N2O abuse and vitamin B12 deficient patients. Follow-up studies with more cases would be beneficial to confirm the unique axonal dysfunction pattern in N2O abuse and to explore treatment strategies for the abuse of the inhalant based on its axonal pathophysiology.In summary, the present study has revealed that the nerve excitability test could detect motor and sensory axonal dysfunction in both NThe raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.This study was carried out in accordance with the recommendations of the Joint Institutional Review Board, Taipei Medical University with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Joint Institutional Review Board, Taipei Medical University.JT and J-YS contributed to the study design. JT, H-JC, T-SC, H-YW, and J-YS contributed to the data collection. JT, T-SC, J-YS, and CL contributed to the data analysis and interpretation. JT, J-YS, and CL contributed to the manuscript preparation. All authors approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


BackgroundPostoperative management in patients undergoing craniotomy is unique and challenging. We utilized a population of patients who underwent bilateral extracranial-to-intracranial (EC-IC bypass) revascularization procedures for moyamoya disease and hypothesized that 1 gram (gm) of intravenous (IV) acetaminophen given immediately after intubation and again 45 minutes prior to the end of craniotomy may be more effective than saline in minimizing opiate consumption and decreasing pain scores.MethodsIn a double-blind, randomized, placebo-controlled crossover pilot study, 40 craniotomies in 20 patients were studied. A random number generator assigned patients to receive either 1 gram of IV acetaminophen or an equal volume of normal saline immediately after intubation and again 45 minutes prior to the end of their first operation. For the second surgery, patients received the study drug  that they did not receive during their first surgery.ResultsIn the IV acetaminophen group, the average 24-hour postoperative fentanyl equivalent consumption was decreased but the difference was not statistically significant: 228 micrograms compared to 312 micrograms in the placebo group (Figure ConclusionOur study demonstrates that in patients receiving bilateral craniotomies for moyamoya disease, IV acetaminophen when given immediately after intubation and again 45 minutes prior to closure does not significantly decrease 12- or 24-hour postoperative opiate consumption. Postoperative management in patients undergoing craniotomy is unique and challenging. An ideal anesthetic would dissipate rapidly, permitting the patient to participate in a postoperative neurologic exam to identify any new deficits while still in the operating room. Accordingly, practitioners may minimize opioid use with the result that post-craniotomy pain is often undertreated -3. In adAlternate modalities for postoperative pain control after craniotomy have been explored, including non-steroidal anti-inflammatory drugs (NSAIDs), dexmedetomidine, gamma-aminobutyric acid (GABA) analogs/gabapentinoids (e.g. gabapentin), acetaminophen and supplemental regional anesthesia. NSAIDs have been shown to decrease postoperative analgesic requirements, however, they may impair surgical hemostasis and contribute to postoperative bleeding . DexmedeAcetaminophen is a well-tolerated and effective analgesic that can be used in an intravenous (IV) formulation perioperatively, to help manage pain. The mechanism of action of acetaminophen is largely undetermined; however, it is thought to function through central processes, including effects on prostaglandin production, serotonergic, opioid, nitric oxide (NO), and cannabinoid pathways . The intWhile studies have shown that a single dose of intravenous (IV) acetaminophen given once intraoperatively , and re-We utilized a unique population of patients who underwent bilateral extracranial-to-intracranial (EC-IC bypass) revascularization procedures for moyamoya disease (ICD-10: I67.5). Each patient underwent two identical surgeries and, therefore, was able to serve as their own control. This unique experimental design and the use of two doses of IV acetaminophen is a novel approach in assessing the effectiveness of IV acetaminophen for postoperative pain after craniotomy.PatientsThis is a double-blind, randomized, placebo-controlled pilot study, approved by the Institutional Research Board of Stanford University. Forty craniotomies in 20 patients were studied. Inclusion criteria for this study included patients aged over 18 years, patients presenting for bilateral EC-IC bypass revascularization surgery for moyamoya disease, and no preoperative or postoperative language deficits. Exclusion criteria were pre-existing hepatic dysfunction, a history of substance abuse, allergy, or intolerance to acetaminophen or any associated excipients, patient refusal, chronic pain, pregnancy, and previous craniotomy.AnesthesiaAll patients included in the study were given a standard anesthetic regimen for both surgeries: Pre-medication with midazolam 1-2 milligrams (mg) in the preoperative holding area was given at the discretion of the anesthesiologist for anxiolysis. At the time of induction, fentanyl 7-9 micrograms (mcg)/kilogram (kg) was administered in divided doses, followed by 0.5 mg/kg propofol and 0.6 mg/kg rocuronium. Patients then underwent endotracheal intubation. Dexamethasone 8 mg IV was given pre-incision to reduce surgical swelling and for postoperative nausea and vomiting (PONV) prophylaxis. Ceftriaxone 1 gm IV or cefazolin 2 gm IV was given for surgical site infection prophylaxis. Patients were maintained on a mixture of 50% nitrous oxide, 50% oxygen, 0.5 age-adjusted minimum alveolar concentration (MAC) isoflurane or sevoflurane, and a remifentanil infusion of 0.05 - 0.2 mcg/kg/minute (min) titrated to obtain hemodynamic stability. Cerebral perfusion pressure was maintained by keeping mean arterial pressure between 80 and 110 mmHg. The adequacy was often assessed using electroencephalographic and evoked potential techniques. Patients who were determined by history to be at higher risk for PONV received propofol 50 mcg/kg/min as a substitute for nitrous oxide. All patients were monitored with invasive arterial blood pressure monitoring. Patients who underwent combined direct-indirect EC-IC bypass (n= 16) received a central venous catheter and were cooled by way of a water circulation blanket to achieve a target temperature of 33 degrees Celsius at the time of cross-clamping of an M4 branch of the middle cerebral artery (MCA). Such patients were re-warmed with a target temperature of > 35 degrees Celsius at the time of extubation. Patients undergoing only an indirect EC-IC bypass did not receive central venous catheters or cooling. All patients received ondansetron 8 mg and metoclopramide 10 mg 30 minutes prior to extubation. All patients were extubated and evaluated in the operating room after discontinuing the remifentanil infusion and then transferred to the intensive care unit for subsequent monitoring.Study protocolA random number generator was used by the hospital pharmacy to assign patients to receive either 1 gm of IV acetaminophen or an equal volume (100 milliliters) of normal saline immediately after intubation and again 45 minutes prior to the end of their first operation. For the second surgery, patients received the study drug  that they did not receive during their first surgery, both immediately after intubation and again 45 minutes prior to the end of the procedure. The average length of surgery was 396.5 minutes. Each patient served as their own control.Anesthesiologists were not blinded to which study drug the patient received, nor were they involved in postoperative pain assessment or treatment. Patients were managed in an identical manner intraoperatively, according to the aforementioned study protocol. All patients were extubated at the conclusion of the surgery and transferred to the intensive care unit (ICU) in the same manner. Upon arrival to the ICU, an information packet was given to the bedside nurse and attending physician, both of whom were blinded to the intervention that had been given in the operating room. Routine nursing assessments were conducted per protocol by the nursing team for the next 24 hours. Each patient’s opioid consumption, pain scores, and antiemetic consumption were monitored and recorded in the electronic medical record. In addition to the study drug, a standard analgesic regimen, consisting of fentanyl, hydrocodone, and hydromorphone, was administered to all patients at the discretion of the ICU medical and nursing teams.Outcomes measuredPrimary outcomes for the 40 craniotomies in 20 patients included in this study were postoperative opioid requirements and postoperative pain scores over the first 24 hours. The secondary outcome was antiemetic use.PatientsThe majority of our study patients were female , and the average age was 37.8 years. The average time between surgeries was 11 days . Sixteen patients received bilateral combined direct-indirect EC-IC surgery. Three patients received bilateral indirect EC-IC surgery. One patient received both indirect and direct EC-IC surgeries.Postoperative opioid consumptionIn the IV acetaminophen group, the average 24-hour postoperative fentanyl equivalent consumption was decreased but the difference was not statistically significant: 228 mcg as compared to 312 mcg in the placebo group  did not affect post-craniotomy morphine consumption , and a sGiven the data presented above and the practice of anesthesia in today’s cost-conscious environment, providers might be discouraged from utilizing IV acetaminophen as an adjunct to treat post-craniotomy pain. However, given that IV acetaminophen has been shown to improve patient satisfaction after craniotomy and has been shown to be equally effective as morphine in acute pain, providers may consider utilizing oral or rectal formulations of acetaminophen as part of a multimodal treatment approach.There are a number of limitations to our study, including that it was underpowered: a post hoc power analysis indicated an achieved power of 0.4 and suggested that an n of 50 would be needed to detect a statistically significant acetaminophen effect during the first 12 hours after surgery. Unfortunately, there were no studies upon which to base a pre-trial power analysis, but we felt that if our results were clinically significant, an n of 20 would be adequate to demonstrate this. A second limitation was that several patients within our cohort requested medications from their home regimen that were not included in our ICU protocol, including benzodiazepines for anxiety (e.g. lorazepam), and pain adjuncts, including the combination drug acetaminophen/butalbital/caffeine. Lastly, of the medications that were included in the ICU postoperative pain protocol, a sliding scale of IV and oral opiate medications were available for the nursing staff to administer and there may have been variation among nursing staff in how much of the PRN (or as needed) medications were given.Clinical studies such as this one present unique challenges in that it is impossible to control for all patient and environmental variables. The intention of our study was to assess the utility of IV acetaminophen in a real-world setting, with the hope that if acetaminophen had a significant effect in postoperative opioid consumption, the results would be apparent despite an n of 20.Pain scoresOur data demonstrate that there was no statistically significant difference in the 12- or 24-hour postoperative pain scores between groups. Pain scores were similar between groups, suggesting that patients were treated similarly between interventions, indicating the adequate blinding of the postoperative ICU medical and nursing staff.Antiemetic useIncreased opiate consumption increases a patient’s risk of undesired side effects, including nausea and vomiting. We hypothesized that decreased opiate consumption would be associated with decreased PONV and, consequently, the consumption of antiemetics. Our data demonstrate no statistically significant difference in antiemetic consumption in the 24-hour postoperative period between the IV acetaminophen and placebo groups. This is consistent with the lack of significance in postoperative opioid consumption discussed previously. This may be attributable to the nature of the surgery itself, as patients receiving craniotomy are known to be at higher risk for PONV . Some daIn conclusion, our study demonstrates that in patients receiving bilateral craniotomies for moyamoya disease, IV acetaminophen, when given immediately after intubation and again 45 minutes prior to closure, does not significantly decrease 12- or 24-hour postoperative opiate consumption, although the amount of opiate given was noted to be less in the IV acetaminophen group. There was no difference in the 24-hour postoperative pain scores or antiemetic usage. Despite our small sample size of 40 craniotomies in 20 patients, we believe our study answers a novel question in that a pre-emptive dose of IV acetaminophen given before incision, combined with a second dose given near the end of surgery, does not appear to add a significant opioid-sparing effect on postoperative pain control but may be a useful adjunct in the multimodal pain management strategy after craniotomy.


Acute abdominal pain is a common clinical problem in emergency and non-emergency cases accounting for 5 to 10% of all referrals to the emergency department. Studies have indicated that these widely differentiated diagnoses are common to these complaints. Considering the high prevalence of this complaint in the patients and the wide range of its differential diagnosis, this review study was designed and evaluated aiming at investigating the causes of acute abdominal pain with a focus on assessing the position of ultrasound as a diagnostic tool in the emergency department.This article was conducted as a narrative review of selected articles from 2005 through 2019. By comparing them, a comprehensive review of ultrasound role was conducted in patients with acute abdominal pain referring to the emergency department.In this review study, we attempted to use the articles of the clinical approach, the required laboratory tests, the disadvantages and advantages of each imaging technique, the differential diagnosis for acute abdominal pain according to the location of the pain, and the position of ultrasound as a diagnostic aid tool. Eventually, the proposed protrusion will be considered in dealing with a patient with acute abdominal pain.Regarding the wide range of causes providing multiple differential diagnosis, as well as the limited time of the health team in the emergency department for diagnostic and therapeutic measures, particularly in time-sensitive clinical conditions, ultrasound offered by emergency medicine specialists as a diagnostic aid is considered to improve the overall diagnosis and treatment of patients, thereby reducing complications. Acute abdominal pain is one of the most common complaint of patients referring to the emergency department (ED), accounting for 5 to 10% of all referrals to this department . The higThis review study was conducted using PubMed, Scopus, EmBase, ScienceDirect and Google Scholar databases. Articles selected from those published from 2005 through 2019. This article was conducted as a narrative review and does not include any independent data derived from direct clinical intervention or fieldwork.Finally, selected articles were used in writing this overview. By comparing them, it was attempted to complete a comprehensive review of ultrasonography role in patients with acute abdominal pain referring to the ED.The most important part of evaluating a patient with acute abdominal pain is history of presenting illness . In acutAbdominal pain characteristics are helpful in determining its physiopathology. The aching or dull pain is due to activation of visceral neural fibers, which may result in stretching, increased peristalsis, or ischemia. An example of activation of these nerves is colonic abdominal pain in the small bowel obstruction . In diseRepeated pain is similar in kidney stones, diverticulitis, and gallstones, and in contrast, newborn pain can be seen in some cases such as appendicitis –28. The After acquiring the history of presenting illness, physical examination is the next step in limiting the diagnosis. At the beginning of the physical examination, it is important and helpful to consider the patient’s general appearance, such as being comfortable or discomfortable, slimming or obesity, pallor, sweating, or sleepiness, and jaundice. A patient who is pale, confused and distressed has more likely a more severe disease. Certainly, in older patients, the patient’s response to severe illness may be less than usual. Pain induced by the slightest movement of the abdomen increases the suspicion of peritonitis, while in the patient’s renal colic, the patient is constantly moving, even while lying on the bed , 23, 35.Laboratory tests should be requested by considering a specific clinical question. In patients with abdominal pain, tests checking for systemic diseases are clinically important. The most commonly used tests in the ED for patients with acute abdominal pain include complete blood count (CBC), blood urea nitrogen (BUN), creatinine (Cr), serum electrolytes, cardiac enzymes, liver function tests, and urine analysis. Other tests after history taking and physical examination and based on a specific diagnosis should be requested . LeukocyImmediately after clinical evaluation, there is a considerable doubt about the urgency of the patient’s condition . ClinicaIn the past, plain radiography, owing to its low cost and availability, was used as the primary imaging modality for patients with abdominal pain. Certainly, with the more accessible alternative methods, its use has become controversial. It is suggested that plain radiography should be used only in cases of intestinal obstruction, perforation, foreign body ingestion or catheter location . Using pThere are considerable sensitivity and specificity for several diseases causing abdominal pain. In cases where multiple diagnoses are commonly suspected, a very good diagnostic test is recommended. In stable patients whose pathology does not have a clear surgical procedure, but in differential diagnosis of the disease, they have important abdominal pathologies, CT scan is a good diagnostic test. We should consider the risk of future exposure to radiation in patients who are supposed to be CT. When using contrast, its cost / benefit should be measured . CT-angiA total of 5–10% of the complaints of patients referring to the emergency department constitute acute abdominal pain, and treatment based on physical examination and laboratory test results can lead to delayed treatment or inappropriate diagnosis –59.In contrast, ultrasonography with broad availability, relatively low cost and absence of radiation, has a unique advantage over CT-Scan as an emergency diagnostic tool . MoreoveIn general, the most common indications of abdominal ultrasound in acute ill patients are blunt trauma, acute abdominal pain and undifferentiated hypotension . HoweverAcute abdominal pain is one of the most common complaints of patients referring to the emergency department. Considering the wide range of causes causing multiple differential diagnoses, as well as the limited time of the health team in the emergency department for diagnostic and therapeutic measures, particularly in time-sensitive clinical conditions, ultrasound can be given by EMP as a diagnostic aid, which is considered to improve the overall diagnosis and treatment of patients, thereby reducing complications and complications. Based on the findings and reviewing the literatures, an algorithm has been prepared by the authors as a suggestion for diagnostic approached to a patient with acute abdominal pain using ultrasound in emergency department which is displayed in Regarding the wide range of causes providing multiple differential diagnosis, as well as the limited time of the health team in the ED for diagnostic and therapeutic measures, particularly in time-sensitive clinical conditions, US offered by EMPs as a diagnostic aid is considered to improve the overall diagnosis and treatment of patients, thereby reducing complications.


Pain is one of the most burdensome and prevalent symptoms cancer patient report and it has severe negative impact on patient’s quality of life. The aim of this study is to estimate the prevalence of pain and to test the association between demographic, clinical, psychological factors, and self-assessed pain in Chinese cancer population.A total of 553 cancer patients were recruited in this cross-sectional study. Patient’s basic demographic data was collected by a study-designed information sheet, and patient’s pain, sleep disturbance and psychological distress were assessed by several validated measurements . Descriptive statistics and hierarchical multiple regression analyses were performed.Of the 553 patients, 411 (74.32%) patients reported that they experience some degree of pain. Fear of progression, anxiety, insomnia, and depressive symptoms were significantly associated with different subscales and the overall pain score in bivariate correlation matrix. Insomnia, depressive symptoms, and fear of cancer progression were significant independent factors of cancer pain on multivariate analyses.Psychological factors play a great role in the relationship between objective pathophysiology and patient’s subjective experience of pain. It is important to evaluate each individual in detail with respect to psychological distress and pain severity when planning treatment and rehabilitation. Suffering comes in many ways for cancer patients, and pain is one of the most burdensome and prevalent symptoms they report. Over 30% of cancer patients describe their pain as distressing or even intolerable . Cancer Pain has severe negative influence on cancer patient’s quality of life (QoL). Patients often report that pain prevents them from focusing or thinking, and that it makes difficulty in performing normal daily activities . StudiesPain is influenced by several physiological, psychological, and behavioral factors . StudiesAs suggested by the biopsychosocial models, an increasing number of researchers have delineated psychosocial variables to be important correlates of pain intensity . HoweverIn the current study, we aim to (1) estimate the prevalence of pain in Chinese cancer population using validated measurements; (2) test whether demographic, clinical as well as psychological factors are correlated with cancer pain; and (3) assess the relevance between pain and FoP. We hypothesize that: (1) compared to demographic and clinical variables, psychological factors play greater role in patient’s self-perceived pain; (2) anxiety, depression, and insomnia symptoms are positively associated with cancer pain; and (3) patients who report higher FoP are more likely to report greater pain.This is a cross-sectional study that involved three main hospitals in southern China. A power analysis was performed before recruitment to determine study sample size. All participants were recruited from the department of oncology , department of breast surgery , and department of radiotherapy  from January to October 2018. To be included in the study, participants needed to: (1) be above 18 years old; (2) had a clear diagnosis of cancer; (3) be able to read and write Mandarin or Cantonese. Participants were excluded if they had disturbance of consciousness, blind, or deaf.Patient’s basic demographic  and clinical  data were collected by a specific question sheet. Information about patient’s treatment received (chemotherapy and radiotherapy), smoking behavior, and physical comorbidity were assessed by “Yes/No” questions. Patient’s personality tendency was measured by a single question derived from the Chinese version Personality Traits Questionnaire : what doThe MPQ-SF  is one oThe AIS  is commoThe FoP-Q-SF is a 12-item scale used to assess cancer patient’s fear of progression. It is the short form of the original 43-item Fear of Progression Questionnaire (FoP-Q) . All of The PHQ is a 9-item self-assessed measure that evaluates the degree of an individual’s depressive symptoms. The item of PHQ ranges from 0  to 3   and it hThe GAD is a 7-item scale used to measure a person’s anxiety level. Response options are not at all, several days, more than half the days, and nearly every day, rated as 0, 1, 2, and 3, respectively . The oriThe Life Stress Inventory was developed to test the relationship between illness and stress . It is aPatients were consecutively recruited from three hospitals. All patients were approached in the waiting room before their appointment with their oncologist and were asked for participation. For those who showed interest in participating, a written informed consent form was provided, then they were asked to complete the information sheet and all scales. Participants were ensured that their personal information would be kept confidential and they could withdraw their participation at any time. The hospital Research Ethics Committee examined and approved the study (Ref No: NFEC-2018-038).t test for independent samples. Analysis of variance and post hoc test were used to identify group effects. Continuous variables that were not normally distributed were analyzed using Mann-Whitney U tests or Kruskal-Wallis tests (K-W tests), as appropriate. The associations between continuous variables were assessed using Pearson’s correlation analysis if the variables were normally distributed, otherwise, Spearman’s correlation was utilized. Hierarchical regression analyses were subsequently conducted to ascertain the associated factors of cancer pain . Three blocks were orderly included in each regression analyses. Demographic factors were entered in the first block, followed by the clinical/treatment factors, and the final block involved the psychological variables.Statistical analyses were preformed using SPSS version 22.0 and the cutoff for statistical significance was set at 0.05 (2 sided). Descriptive statistics were used to calculate frequencies, means, and standard deviations. Difference in means were investigated using a A total of 887 patients were invited to participate the study and 566 (63.81%) of them agreed. Thirteen patients were then excluded from the study because they were teenagers (age under 18 years). Finally, 553 patients completed the survey. The mean age of patients is 47.23 . The majority of the participants were female (91.7%), married (87.5%), diagnosed with breast cancer (84.6%), non-current smoker (96.2%) and had received chemotherapy (90.6%), and radiotherapy (86.6%). All participants were currently receiving active treatment (radiation/chemotherapy/drugs). Less than half of the participants experienced clinical insomnia (40.7%), FoP (29.8%), depressive or anxiety symptoms . Of the 553 participants, 142 (25.68%) patients reported no pain , and the remaining 411 (74.32%) patients reported some degree of pain. Patient’s demographic, clinical as well as psychological characteristics are presented in On univariate analysis, low monthly income, insomnia, FoP, depressive, and anxiety symptoms were significantly associated with greater cancer pain . Patients who were older were more likely to report higher scores on PRI-total and VAS. Compared to pessimists, optimists reported lower ratings on PRI-total and PPI. Additionally, we found patients who were experiencing more stressful life events were more likely to report higher levels of pain on PRI-total and PPI see .r = 0.052).The corresponding factors that shown significant correlation with cancer pain in previous univariate analyses were then introduced in each regression model  accordingly as independent variables. Demographic, clinical, and psychological factors were orderly entered in blocks as model 1, 2, and 3. The Durbin-Watson (DW) value of each model, which was a number that tested for autocorrelation in the residuals, was all satisfactory (ranged from 1.820 to 2.184). The variance inflation factor (VIF) , which qP < 0.001), VAS  and PPI , which demonstrated that those who were depressed were at higher risk of experiencing greater pain. FoP was the second strongest factor associated with PRI-Total  and VAS , however, it was not significantly associated with PPI. Insomnia symptom was positively associated with PRI-Total  and PPI , however, it did not significantly correlate with VAS. Age, and anxiety symptom, were not statistically significant in all regression analyses. In all, for each regression model, psychological variables showed stronger association with patient’s pain experience than demographic as well as clinical factors.The current study is one of the few epidemiological studies that examined the factors associated with cancer patient’s pain experience in mainland China, and it is the first study to investigate the association of FoP and self-perceived pain. In the past, pain was seen only as a biomedical issue. However, nowadays, people have widely recognized the fact that psychological, social as well as environmental factors significantly influence a patient’s pain experience . StudiesIn present, pain is considered as the fifth vital sign of a cancer patient’s well-being along with signs of respiration, blood pressure, temperature, and heart rate . Our stuEvidence is irrefutable that psychosocial factors play a great role in the relationship between objective pathophysiology and patient’s subjective experience of pain . As hypoWhen coping cancer or other life-threatening diseases, personality is one of the most clearly documented variables  and has Inconsistent with previous findings , this stThere are a number of limitations of the current study. First of all, this study was based on a cross-sectional cohort, the causal relationships between tested variables and cancer pain are still unclear. Longitudinal cohort studies are necessary to identify causal associations. Second, patient’s insomnia, anxiety as well as depressive symptoms were measured only by self-rated questionnaires. No psychiatrist was involved to confirm clinical diagnosis. Also, single item question was used to measure patient’s personality tendency and no psychometric information was provided. Assessment bias may exist and can hardly be eliminated from cross-sectional studies. Further studies using more extensive and objective measurement tools would be beneficial. Third, only hospitals in southern China were included and the majority of the participants were female patients diagnosed with breast cancer. A potential sample bias may exist, and the research findings cannot be generalized to the entire Chinese cancer population. A national study with various cancer populations would be beneficial. Last but not least, more information about the clinical/treatment characteristics of the sample should be included, such as time since diagnosis and surgery type, as those factors may also impact patient’s pain experience.Multidisciplinary groups are necessary in oncology settings to integrate care for pain management. It has been proved by previous meta-analysis and high-quality RCT studies that psychological and behavioral interventions could clinically improve patient’s cancer-related pain . HypnosiThis study demonstrated that insomnia, depressive symptom, and fear of progression in cancer patients generally links to greater self-assessed pain. On the basis of the findings, it is important to evaluate each individual in detail with respect to psychological distress and pain severity when planning treatment and rehabilitation. Multidisciplinary helping groups and relevant coping skill training should be provided to improve patient’s pain management as well as their quality of life.The datasets for this manuscript are not publicly available because further articles will be published based on the database. Requests to access the datasets should be directed to 306850475@qq.com.This study was carried out in accordance with the recommendations of Clinical Research Guideline, Nanfang Hospital Research Ethics Committee with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Hospital Research Ethics Committee (Ref No: NFEC-2018-038).YZ and YY: study design. XT, HW, and HS: data collection. WL, TL, and JZ: data analysis and interpretation. YZ, XT, WL, and HW: drafting of the manuscript. BZ and YY: revising of the manuscript. All the co-authors contributed to the approval of the final version for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Chronic pain has a negative impact on quality of life and psychological well-being. The objectives of this study are to investigate the psychological status and quality of life in backache patients before and after spinal traction and reflect how this maneuver is effective in treating backache.Forty-seven backache patients completed the hospital anxiety and depression scale (HADS) and Short-Form 36 Health Survey (SF-36) before and after treatment with spinal traction. Forty-eight healthy controls, matched with patients for age and sex, completed the same questionnaires. Pain was assessed before and after the maneuver using a visual analog scale (VAS). Traction was added to patients’ medications which were not enough to control patients’ symptoms and did not change during the course of traction.Before spinal traction, the mean VAS score was 7 ± 1.36, abnormal levels of anxiety and depression were found in 36.17% and 40.43%, respectively, of patients, and all SF-36 domains of the study population, except for physical functioning, showed mean scores < 50%. After spinal traction, the mean VAS score dropped significantly to 5.44 ± 1.51, abnormal levels of anxiety and depression became 14.9% and 21.3%, and all SF-36 domains improved significantly, with six of the eight domains showing mean scores > 50%. There were significant differences regarding all SF-36 domains, and anxiety and depression scores between patients and controls, in favor of controls, before traction. These differences disappeared after spinal traction.Pain, psychological status, and quality of life improved when spinal traction was added to medications reflecting its efficacy for patients with backache. Chronic back pain is a common health problem resulting in significant personal, social, and occupational impairment; role disability; and health care utilization .Reduced quality of life is common among patients suffering from chronic low back pain . AnxietyAlthough there is conflicting evidence for its efficacy for patients with low back pain, there is preliminary evidence that lumbar traction produce positive results in nerve root compression symptoms. Regarding degenerative and discogenic pain, data are debatable . By usinThe present study aims to assess the psychological status and quality of life in a group of backache patients before and after spinal traction, to reflect how this maneuver is effective in treating their conditions and whether longer duration of treatment is more beneficial, and, finally, to detect correlations and associations among variables studied.This prospective study was carried out on 47 recruited patients seeking treatment at the Physical Medicine, Rheumatology and Rehabilitation Department, Menoufiya University Hospitals, in the period between January and July 2015.Two groups of patients were included in the present study: the first being those with the diagnosis of prolapsed lumbar disc and the second with lumbar spondylosis “osteoarthritis” diagnosis. Patients were diagnosed to have lumbar spondylosis based on clinical examination and plain x-ray lumbosacral spine. Patients with prolapsed lumbar disc were diagnosed on the basis of clinical examination and MRI lumbosacral spine. Patients showed only some improvement on medical treatment, NSAI drugs, muscle relaxants, and drugs for neuropathic pain, which was continued and not changed during the course of spinal traction.In addition to non-consenting patients, patients with the following conditions were excluded from the present study: ligamentous instability, osteomyelitis, diskitis, primary or metastatic spinal cord tumor, severe osteoporosis, myelopathy, fibromyalgia, or untreated hypertension. Patients currently treated for psychiatric disorders, or those who had past history of psychiatric disorders, were also excluded.Forty-eight health controls, matched with patients for age and sex, were recruited from employees working at the Faculty of Medicine, Menoufia University, and its hospitals.For recording socio-demographic data, medical history, results of clinical examination, and radiological investigations (plain x-ray and MRI), an interviewing questionnaire was used.The intensity of the pain was measured using a visual analog scale (VAS) in which the intensity of pain was classified as 0 to 10, as follows: 0–1 = no pain, 2–3 = mild pain, 4–5 = moderate pain, 6–7 = intense pain, and 8–10 = extreme pain.Depressive and anxiety symptoms were assessed by an Arabic version of Hospital Anxiety and Depression scale . HAD scaHealth-related quality of life was assessed by applying the Arabic version of the Short-Form 36 Health Survey (SF-36) . This isELTRAC 471, ENRAF-NONIUS, Netherlands, is a microcomputer-controlled unit for continuous and intermittent spinal traction. In the ELTRAC 471, the traction force is controlled and monitored by the built-in microprocessor. The tension in the cord is measured electronically and compared with the set value.A further advantage of the electronic traction control is that the speed of applying and releasing the traction force can be adjusted. In addition to the electronic safety system, the unit is also provided with a mechanical traction limiting system and the patient can stop the switch which enables the patient to terminate the session.Patient who had undergone lumbar traction was exposed to a superficial heat physical therapy at the lumbosacral area by using infrared therapy for a 10-min duration. This was immediately followed by lumbar traction session. The duration of the lumbar traction session was 20 min.The patient was lying down in supine position. The mode of application of lumbar traction was intermittent application determined by patient’s body weight and gradually increased in further sessions according to patient’s tolerance. Patients were divided into two groups, the first group received 4 weeks of spinal traction (28 patients 59.5%) and the second received more than 4 weeks and up to 12 weeks of treatment (19 patients 40.5%).Controls filled the sociodemographic sheet, and both hospital anxiety and depression scale (HADS) and Short-Form 36 Health Survey.p value < 0.05. The Man-Whitney test was used to compare the controls’ and patients’ results once before the spinal traction and another the time after.All analyses were done using the software SPSS 20. IBM Corp. Armonk, NY, USA. As variables were not normally distributed, Wilcoxon signed ranks test was used to compare the patients’ results before and after spinal traction, and Spearman correlation test to detect any correlations between tested variables. Chi-square test and Fischer’s exact test were also used to detect any associations between different variable improvements after spinal traction. Statistically significant findings were determined by a two-tailed The present study included 47 patients. They were 29 females (59.6%) and 18 males (40.4%), and the mean age was 42.55 ± 13.13. Patients were presented with two main diagnoses, prolapsed lumbar disc , and spondylosis . The duration of illness ranged from few months and up to 10 years with mean ± SD 24.28 ± 27.84, and traction duration ranged from 4 to 12 weeks.Forty-eight controls were included in the study. They were 26 females (54.16%) and 22 males (45.84%), and the mean age was 42.55 ± 13.13.Only six patients scored below 6, mild to moderate pain, while all other patients’ scores reflected intense and extreme pain. Before starting spinal traction, VAS score ranged from 3 to 9 with mean ± SD 7 ± 1.36. Following lumbar traction, VAS score ranged from 2 to 9 with mean ± SD 5.44 ± 1.51.Before starting spinal traction, abnormal levels of anxiety and depression, HADS 11–21, were found in 36.17% and 40.43% of patients, while after spinal traction these percentages became 14.9% and 21.3%.Before spinal traction, anxiety and depression scores were 9.57 ± 3.57 and 9.68 ± 3.26, respectively. After spinal traction, the scores became 7.57 ± 3.15 and 7.96 ± 2.77. No differences were found between male and female patients regarding anxiety or depression before spinal traction.Table z test = − 2.98 p = 0.003).Patients who underwent spinal traction for more than 4 weeks did not show more improvement than patients who received 4 weeks of treatment, except for improvement in SF-36  of patients complaining of backache. If adding patients who scored 8–10, borderline abnormal, the percentages will rise to 76.59 and 78.72%, respectively.A Pakistani study investigated the prevalence of anxiety and depression in 140 patients with chronic low back pain using HADS revealed that 16.4% and 12.1% of the patient scores for anxiety and depression, respectively, were abnormal (HADS 11–21). A study of 70 German patients with back pain reported 36% of patients with abnormal anxiety (HADS-A > 10) and 29% with abnormal depression (HADS-D > 8) .According to Kayhan and his colleagues, mood and anxiety disorders were more commonly seen in patients with lumbar disc herniation than in control subjects . Also, tIn the present study and after spinal traction, anxiety and depression scores measured by HADS dropped significantly from 9.57 ± 3.57 and 9.68 ± 3.26 to 7.57 ± 3.15 and 7.96 ± 2.77, respectively. Following traction, the percentages of patients who scored (11–21) on HADS dropped from 36.17% and 40.43% to 14.9% and 21.3% for anxiety and depression, respectively.As shown in Table According to Bentsen SB and colleagues , reducedp = 0.047).Despite that the scores of VAS and HADS for both anxiety and depression significantly decreased after spinal traction, no correlations were found between these three variables before traction. Comparing patients’ results before and after traction, chi-square test did not show any significant association between the improvement of VAS scores and any other improvements. Again, and at the same time, chi-square test showed an association, although weak, between the improvement of SF-36 bodily pain domain and depression  and the antecedent hypothesis (anxiety disorders precede the development of chronic back pain) . AccordiConsidering similar biological pathogenesis, the development of pain, depression and anxiety share the participation of neurotransmitters’ such as serotonin, norepinephrine, gamma-amino-butyric-acid, glutamate, adenosine, cannabinoids, and many other neuropeptides . FunctioFrom the results shown in Tables It was not unexpected that depression scores correlated negatively with each of SF-36 vitality and general health perception as this reflects some genuine depressive features—fatigue and negative self-perception. The same is also true in case of anxiety and vitality.Lamé IE and his colleagues investigated pain cognitions and quality of life in a heterogeneous group of 1208 chronic pain patients. Patients with low back pain and multiple pain localizations experienced most functional limitations . Pain caSo backache interfering with patient’s different aspects of life, affecting his/her quality of life, including mental health, becomes associated with anxiety, phobia, of experiencing such pain while doing whatever activity “Pain catastrophizing.” Pain catastrophizing affects patient quality of life more and more. Depression increases secondary to the perception of impaired quality of life and strongly correlated with anxiety increase. While improving and when not experiencing pain in different situations, anxiety decreases, quality of life improves, and so does depression.The present study had several limitations, of which the small number of patients was the most important.From the present study, we can reach some conclusions. First, spinal traction combined with medical treatment is effective for treating patients with chronic backache, and durations of treatment more than 4 weeks are not so much superior. Second, patients with chronic backache experience psychological disturbance in the form of anxiety and depressive symptoms which could worsen the patients’ conditions. Third, together with anxiety and depression, pain affects the quality of life of patients with chronic backache. Finally, further revisions of the usage of pain measurements that relate pain to patients’ activities, and not a general subjective measurement, should be considered.