Refractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a series of patients with refractory migraine treated with intravenous ketamine in the hospital setting.Based on retrospective chart review, we identified six patients with refractory migraine admitted from 2010 through 2014 for treatment with intravenous ketamine. Ketamine was administered using a standard protocol starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h as tolerated until the target pain score of 3/10 was achieved and maintained for at least 8 h. Visual Analogue Scale (VAS) scores at time of hospital admission were obtained as well as average baseline VAS scores prior to ketamine infusion. A phone interview was conducted for follow-up of migraine response in the 3 to 6 months following ketamine infusion.The study sample had a median age of 36.5 years (range 29–54) and 83% were women. Pre-treatment pain scores ranged from 9 to 10. All patients achieved a target pain level of 3 or less for 8 h; the average ketamine infusion rate at target was 0.34 mg/kg/hour (range 0.12–0.42 mg/kg/hr). One patient reported a transient out-of-body hallucination following an increase in the infusion rate, which resolved after decreasing the rate. There were no other significant side effects.IV ketamine was safely administered in the hospital setting to patients with refractory chronic migraine. Treatment was associated with short term improvement in pain severity in 6 of 6 patients with refractory chronic migraine. Prospective placebo-controlled trials are needed to assess short term and long-term efficacy of IV ketamine in refractory chronic migraine.The online version of this article (doi:10.1186/s10194-016-0700-3) contains supplementary material, which is available to authorized users. Chronic migraine and refractory migraine have long challenged clinicians. In the United States, chronic migraine prevalence is nearly 1% and results in enormous impact on headache-related disability, including higher Migraine Disability Assessment Test (MIDAS), reduced health-related quality of life (HRQoL), increased depression and anxiety (PHQ-4 and GAD-7 respectively), compared to episodic migraine . ChronicRefractory migraine is included in ICHD-2  and ICHDOne candidate treatment for intractable migraine is ketamine. Intravenous ketamine has been studied in various refractory pain conditions including complex regional pain . IntranaKetamine is a dissociative anesthetic that acts on glutamate binding sites at the N-methyl-D-aspartate (NMDA) receptor as well as at opioid, monoaminergic, cholinergic, nicotinic, and muscarinic receptors . There iHerein, we report the effect of IV ketamine on a series of six patients with intractable migraine treated with escalated doses on an inpatient basis.We performed a retrospective chart review study. From 2010 until 2014, a total of six patients were admitted for treatment with continuous intravenous ketamine to Mount Sinai Beth Israel Hospital in New York. Data were collected from charts obtained from the medical record department and electronic medical records (PRISM). The study was approved by the Mount Sinai Institutional Review Board. Prior to admission, a diagnosis of chronic migraine without aura based on ICHD-2 criteria was made by a headache specialist (Sait Ashina). Demographics, number of prior migraine treatments and current use of medications such as opioids, antidepressants, beta blockers, antiepileptic medications and nonsteroidal anti-inflammatory drugs (NSAIDs) were documented, as well as onset age of migraine diagnosis.All the patients received information regarding side effects and risks associated with the treatment and informed written consent was obtained prior to infusion. Monitoring of the treatment was done according to the ketamine infusion procedure policy of the Department of Pain Medicine and Palliative Care at Mount Sinai Beth Israel  score was used at the moment of admission and follow-up VAS scores at different ketamine infusion rates were assessed from nursing and infusion records. We defined a pain response as a reduction in the initial VAS to a score of three or less. Side effects were identified and reported.We attempted to contact the patients in this retrospective study for telephone follow-up; however, we were only able to reach two of the six patients. During telephone interview, a questionnaire including MIDAS  was admiCharacteristics of patients admitted for ketamine are summarized in Table All of the six patients were started on IV ketamine dose of 0.1 mg/kg/hr. All six patients achieved the target endpoint of a pain score of less than three out of ten sustained for at least 8 h. The intravenous ketamine doses are presented in Table In this small cases series, all six patients with refractory migraine met the target pain relief endpoint with ketamine over a mean infusion of 44 h (range 12–82). Mean ketamine infusion rate at the time of pain relief endpoint was 0.34 mg/kg/hour (range 0.12–0.42). Patients achieved pain relief without substantial adverse effects. One patient reported a brief dissociative experience, which reversed.Intravenous ketamine use in treating refractory depression has recently been well established , 23. StuThe existing literature on IV ketamine for the treatment of headache is limited. Though our case series is modest in size, and in the absence of a contemporaneous placebo group, causal inferences are not possible, we demonstrated short-term success in pain relief in intractable migraine patients with one significant but short-lived adverse event. It is biologically plausible that ketamine could be an effective treatment for intractable headache. Ketamine is an antagonist at NMDA receptors, blocking the excitatory action of glutamate (Glu), a neurotransmitter long implicated in the pathophysiology of migraine . Glu hasTo date, there has been a lack of treatments with reliable abortive effect on migraine aura, the phenomenon attributed to CSD. In the rat-model, both ketamine and the non-specific NMDA antagonist, MK-801 have been shown to block CSD, demonstrated electrophysiologically and by fMRI . In a doOf the patients that completed follow up questionnaires, none reported lasting benefit from ketamine 3–6 months post infusion. Prior publications have reported lasting effects on chronic non-headache pain reduction following long term infusions of more than 4 days. Of note, none of the patients included in this case series received ketamine infusion for more than 4 days. Thus, we propose that future studies target ketamine infusions for at least this duration. Once placebo controlled studies on acute headache relief are performed, studies assessing long-term benefits should begin. Strategies for maintaining the effect of intravenous ketamine infusion should also be studied, such as the ongoing administration of a daily or as needed NMDA receptor antagonist. Researchers have used similar strategies in prior studies, such as with the use of mexiletine following lidocaine infusion for chronic daily headache. In this fashion, agents including dextromethorphan-quinidine, memantine, oral or intranasal ketamine could be used to maintain the benefit from NDMA receptor antagonism following ketamine infusion , 36.This study highlights the need for further research regarding new treatment options for patients who suffer daily consequences of refractory migraine and have failed many abortive and preventive medications. Our IV ketamine infusion protocol, based on gradually dose escalation, relieves pain without substantial adverse effects. However, future study of this benefit on short-term headache relief needs to be conducted in a placebo-controlled fashion and this publication may serve as the basis for the design of such a trial.


Breakthrough cancer pain (BTcP) is defined according to its principal characteristics: high intensity, short time interval between onset and peak intensity, short duration, potential recurrence over 24 h and non-responsiveness to standard analgesic regimes. The Edmonton Classification System for Cancer Pain (ECS-CP) is a classification tool that evaluates different dimensions of pain.The aim of this study was to measure prevalence and the main characteristics of BTcP in a sample of advanced cancer patients and to explore the complexity observed when ECS-CP is incorporated into BTcP diagnostics algorithm.Descriptive prevalence study (Retrospective chart review). Davies’ algorithm was used to identify BTcP and ECS-CP was used to recognize appropriate dimensions of pain. The study was conducted in a sample of advanced cancer patients attending hospital outpatient clinic in Lleida, Spain. 277 patients were included from 01/01/2014 to 31/12/2015. No direct contact was made with participants. The following information was extracted from the palliative care outpatient clinic database: age, gender, civil status, cognitive impairment status, functional performance status and variables related to tumour. Only BTcP cases were included.n = 154; 31.6%). Metastases were diagnosed in 83% of the sample. 138 patients (49.8%) were diagnosed with 1 type of BTcP and 139 (50.2%) were diagnosed with more than one type of BTcP. In total, 488 different types of BTcP were recorded , 244 of these types (50%) presented a component of neuropathic pain. Addictive behaviour, measured through CAGE test, was present in 29.2% (N = 81) of the patients and psychological distress was present in 40.8% (n = 113).Prevalence of BTcP was 39.34% (63.9% men). Mean of age was 68.2 years. Main diagnosis was lung cancer  is similar to the one reflected in the existing literature. Study results indicate that the routine use of ECS-CP in a clinical setting allows us to detect more than one type of BTcP as well as additional complexity associated with pain . In 1989, Portenoy and Hagen .Later, BTcP was redefined as a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain . More rePrevalence of BTcP varies between 19 and 95% –11. ThisThe prevalence of BTcP assessed in outpatient clinics is 39.9% and in those assessed in palliative care units, is 80.5% .It is therefore difficult to diagnose BTcP. For this reason, many Scientific Societies related to cancer, palliative care and pain, work to clarify the definition and the accurate diagnosis of BTcP –17.In the same way, different instruments have been defined to facilitate the diagnostic approach of BTcP. We highlight the Alberta Breakthrough Pain Assessment Tool for Cancer Patients , the breTo improve the sensitivity of the diagnosis of BTcP, several authors developed the so-called “Davies algorithm” , recentlLiterature refers to BTcP as a single clinical entity with several possible episodes in a single patient and the fact that more than one different types of BTcP with several episodes each in the same patient has not yet been explored , 23, 24.The pharmacological treatment of BTcP is based on the use of the three-step ladder of the WHO , 26. ConEarly pharmacological approach is the cornerstone of the treatment of BTcP . Its impThe first choice of treatment is always oral and in many cases, for the treatment of BTcP, the choice is fast bioavailability treatments such as fentanyl. The rapid bioavailability of fentanyl-based ROOs may lead to episodes of abuse of these drugs; therefore it is advisable to minimize the risk with a detailed appropriately assessment , 34.The Edmonton Classification System for Cancer Pain (ECS-CP) derives from the Revised Edmonton Staging System (rESS) from which construct, inter-rater reliability, and predictive validity evidence have contributed to the development of the ECS-CP. The five features of cancer pain included -Pain Mechanism (N), Incident Pain (I), Psychological Distress (P), Addictive Behavior (A) and Cognitive Function (C)- have demonstrated value in predicting pain management complexity , 36.The ECS-CP is a clinically relevant systematic framework, which is able to detect differences in salient pain classification features across diverse settings and countries .It is known that BTcP is difficult to diagnose and to treat. We hypothesized that if we add the ECS-CP during the diagnosis process, we find an added complexity together with the incident features of the cancer pain. This is because we can find other characteristics of pain such as the neuropathic component, addiction and psychological discomfort.To describe the characteristics of the population studied and the prevalence of BTcP in a sample of advanced cancer patients treated at an outpatient clinic.To determine the number of different types of BTcP diagnosed in each patient, regardless the number of episodes of BTcP.To explore the different pain features associated to the diagnosis of BTcPTherefore, the objectives of this retrospective review were:This was a retrospective and anonymous database review of the patients attending for the first time at Palliative Care outpatient clinic, which is maintained at the Lleida University Hospital in Catalonia (Spain).This study was approved by the Ethics Committee of the Hospital Universitari Arnau de Vilanova in Lleida. All data-analysis was performed anonymously without an additional informed consent, according to its recommendations. The administrative permissions required were obtained in order to review patient records and use the data.This Palliative Care outpatient clinic attends advanced cancer patients early in the disease course as well as patients that are not receiving active treatment. The patients were referred to the clinic by their reference oncologist and the palliative care consultation team was the responsible organ of the pain management.Inclusion criteria: age > 18 years, diagnosis of advanced cancer  assisted at the outpatient clinic of the Palliative care outpatient clinic suffering, from BTcP due to cancer and without any cognitive impairment (Pfeiffer test ≥ 4 errors). End-of-dose pain was specifically excluded.We defined BTcP according to Boceta et al.  as a traA physician, also responsible for assessing pain and other symptoms, evaluated all the patients attended in the outpatient clinic. Pain was assessed using a Visual Analogic Scale (VAS) and the cut-off value  of patients for their background pain was VAS ≤ 3 during the previous 7 days. All patients who reported adequately controlled background pain (VAS ≤ 3) in the previous week were further evaluated exhaustively. The procedure to diagnose BTcP was done following the algorithm of Davies  and accoThis is the usual protocol applied in order to study pain when a patient is assessed first time at the outpatient clinic.The following information was extracted from the chart review: age, gender, civil status, cognitive status measured with Pfeiffer test , 40, funRelated Factors: predictable, unpredictable or idiopathic .Cause of pain: tumour, treatments received or idiopathic cause.Intensity of pain: measured through a VAS scale. Minimum and maximum intensity were recorded. The difference between VAS minimum intensity (VAS min) and VAS maximum intensity (VAS max) should be ≥ 3 points measured with scale from 0 to 10.We also extracted the information related to BTcP as following:The ECS-CP was applied in order to detect additional pain features other than incident pain in the same patient. The neuropathic component of pain was assessed through the Doleur Neuropathique-4 questionnaire (DN4) , 46 altoFor each pain features detected by the ECS-CP (NIPAC), one point was given.Even if the number of BTcP episodes were specifically registered in the patients files, they were not included in the data analysis.The data included all patients attending the outpatient clinic of the Catalan University Hospital Arnau de Vilanova of Lleida between 2014 and 2015. The information for the study was extracted between June and October 2016.The study was carried out in two separate phases; in the first phase the data analyzed was related to the total number of patients with pain included consecutively in the study and this sample was further studied according to the number of different types of pain found (1 types vs. > 1 type of pain). In the second phase, data analyzed was related to the total number of different types of BTcP individualized after having used the ECS-CP in the diagnostic algorithm and the sample was also further analyzed depending of the pain intensity. We considered mild and moderate pain if the VAS < 7 and severe pain included VAS ≥ 7.P < 0.05).Statistical analyses were conducted using SPSS Statistics 20 (IBM Corporation) and Microsoft Excel (Microsoft Corporation) software . Continu. A total of 488 different types of BTcP were detected (mean of 1.75 ± 0.9 types of BTcP per patient). Up to 5 different types of BTcP were found among the patients and 50,2% of patients (N = 139) accounted for ≥ 2 types of BTcP  between January 2014 and December 2015. 704 of them (55.17%) attended the outpatient clinic. 303 patients had pain, and 277 were diagnosed of BTcP and included to the chart review study. Mean age was 68.2 ± 13 years while men accounted for 67.9% of the sample. Lung cancer (31%) was the most prevalent cancer diagnosis and metastatic disease was found in 83% of the sample. A prevalence of 39.34% of BTcP (277/704 patients) was found. Addictive behavior was detected in 29.2% of the sample and the psychological discomfort was detected in 40.8%. This table also shows the results according to two groups of patients (1 type vs > 1 type). The group of patients with > 1 type was younger , had more metastatic disease  and presented with more psychological discomfort . Patients with 1 type of BTcP presented addictive behavior (CAGE) .Main characteristics of the population studied are showed in Table 1N = 488). The use of the ECS-CP tool on each type of BTcP allowed us to detect that, together with the incident feature of pain, 50% (N = 244) had a neuropathic component. Non-volitional component of BTcP was detected in the 63.7% of the sample. The sum of the different pain features detected by the ECS-CP (NIPAC) when applied on the sample of 488 different types of BTcP is 2.2 ± 1.In Table This retrospective study was designed to determine several outcomes related to BTcP in a sample of advanced cancer patients who attended the outpatient clinic of a University hospital during a two-year period (2014–2015).American Pain Foundation, show a prevalence of 35% for those cancer patients seen on an ambulatory regime.We identified a prevalence of 39.34% of BTcP in the sample of patients screened for the study. The application of Davies algorithm and a close clinical examination were the cornerstone for defining pain. This result is consistent with Deandrea et al.  who afteTo our knowledge, this study provides the first data regarding the fact that a single patient can present with more than one type of BTcP. Previous studies only address this subject as a single patient having different episodes of the same BTcP. On the current study, we found that a total of 488 different types of BTcP were assessed in a sample of 277 patients. Each patient had an average of 1.75 BTcP. We remark that more than half of the patients (139/277) were found to report more than one type of BTcP. Up to 12 patients presented with 4 or 5 different types of BTcP (4.3%) while 127 patients (45.9%) presented with 2 or 3 different types of BTcP.Younger patients and those presenting with metastatic disease variables were found statistically significant.The classification ECS-CP provides further insight into several characteristics of pain like neuropathic, psychological distress and addictive behavior features. As the Incident component of pain is already included in the ECS-CP, all types of pain found in our study had a BTcP component. The addictive behaviour (A) was sensibly higher (29.2%) than the found in the literature. Parsons et al.  and Dev The sample of 488 different types of pain found was further divided according to pain intensity. Only neuropathic nature of pain, the summation of the ECS-CP and the type of cancer showed significant statistical differences.The ECS-CP has demonstrated its utility in routine clinical practice. Arthur et al.  found thHowever the study has limitations; first, the study was carried out in a single institution and data available from medical records were recorded by a single physician during clinical interviews. Second, data from addiction behaviour only included alcohol screening through the CAGE questionnaire.Our study did not aim to analyse any specific pharmacological treatment the patients received. Our study shows a high prevalence of the neuropathic component of BTcP, further studies have to address this finding.This is a retrospective study and prevalence rates are reported from a single institution and a single physician recorded the data available from medical records during clinical interviews.This study includes BTcP and incidental pain in equal terms.Data from addiction behaviour only included alcohol screening through the CAGE questionnaire.This study included a large cohort of patients who had BTcP.This study supports the hypothesis that a single patient can present more than one type of BTcP.This study supports the use of screening tools to better categorize diagnose of Cancer pain.The strengths and limitations of this study are the following:Our study provides data regarding prevalence of BTcP in a palliative care outpatient clinic in a single Teaching Hospital and the result of 39.94% is similar to those found in the literature.This retrospective chart review allows determining the number of different types of BTcP diagnosed in each patient, regardless the number of episodes of BTcP. This is possible with the routine use of the ECS-CP in tandem with the Algorithm of Davies when exploring BTcP in cancer patients.This study explores the different pain features associated to the diagnosis of BTcP. Clinicians have to take into account several pain features such as the neuropathic nature of pain, psychological distress and addictive behaviour, as the optimal therapeutic approach can change.The existence of more than one type of BTcP in each patient adds more complexity to the pain assessment.


Regarding the mental component of HRQoL, depressive and anxiety symptoms, alexithymia, and PI significantly explained 61% of the variance (p < 0.001). The mediation analyses confirmed that alexithymia had a direct effect on the mental component of HRQoL and showed a statistically significant indirect effect on both the physical and the mental components, through the mediation of depressive symptoms. In conclusion, the results of the present study suggested the presence of both a direct and an indirect effect of alexithymia, in particular of the difficulty identifying feeling, on the HRQoL of patients with FM. Indeed, even though the concomitant presence of depressive symptoms is responsible of an indirect effect, alexithymia per se seems to directly contribute to worsen the impact that this chronic pain pathology has on the patients’ quality of life, especially regarding the psychosocial functioning.Pain in fibromyalgia (FM) is accompanied by a heterogeneous series of other symptoms, which strongly affect patients’ quality of life and interfere with social and work performance. The present study aimed to evaluate the effects of alexithymia on both the physical and the psychosocial components of the health-related quality of life (HRQoL) of FM patients, controlling for the concomitant effects of depression, anxiety, and pain. In particular, given the strong interconnection between depression and alexithymia, the relationship between alexithymia and HRQoL as mediated by depressive symptoms was further investigated. Data were collected on a consecutive sample of 205 female patients with a main diagnosis of FM. The results showed that about 26% of the patients showed the presence of alexithymia, as assessed by the Toronto Alexithymia Scale (TAS-20). Clinically relevant levels of depressive and anxiety symptoms were present in 61 and 60% of the patients, respectively. The results of the hierarchical multiple regression analyses showed that pain intensity (PI) and depressive symptoms explained the 45% of the variance of the physical component of HRQoL ( Fibromyalgia (FM) is characterized by widespread musculoskeletal pain, with palpation-specific regions of tenderness, associated with other symptoms, such as fatigue, non-restorative sleep, mood disorders, and cognitive impairment . This chAnother psychological factor that has recently attracted the attention is alexithymia, a multifaceted personality dimension, largely observed in “psychosomatic” disorders . AlexithThe present study aimed thus to evaluate the effects of alexithymia on both the physical and the psychosocial components of the health-related quality of life (HRQoL) of FM patients, controlling for the concomitant effects of depression, anxiety, and pain. In particular, given the strong interconnection between depression and alexithymia, the relationship between alexithymia and HRQoL as mediated by depressive symptoms was further investigated. We hypothesized that the presence of alexithymic trait could negatively influence the impact that FM symptoms had on patients’ daily quality of life, both directly and indirectly.This prospective study was carried out on a consecutive series of FM patients recruited during their first visit at the Fibromyalgia Unit of the “A.O.U. Città della Salute e della Scienza – presidio Molinette” Hospital of Turin. The “A.O.U. Citta della Salute e della Scienza – A.O. Ordine Mauriziano of Turin – A.S.L. TO1 Ethic Committee” approved the study  and all patients provided their written informed consent.At the end of their first visit at the Fibromyalgia Unit, all the female patients with a main diagnosis of FM, made by an expert rheumatologist, and fulfilling the inclusion/exclusion criteria were invited to participate. The main exclusion criteria were: less than 18 years old; low educational level (<5 years) or insufficient knowledge of the Italian language; unstable medical or psychiatric illness or current primary psychiatric diagnosis including severe depression; pain due to traumatic injury or structural/regional rheumatic disease. Out of the 354 consecutive FM patients contacted, 35 refused to participate in the study and 114 were excluded according to the exclusion criteria. A total of 205 patients composed the final sample. Recruited patients arranged an appointment with a trained doctoral clinical psychology student that assessed socio-demographic and clinical characteristics, and administered the pencil-and-paper psychological scales. The appointment lasted approximately 45 min.The pain intensity (PI) was measured using a Visual Analog Scale (VAS) and the Italian Pain Questionnaire (IPQ). Regarding the VAS, patients were asked to rate the average intensity of pain experienced in the last week on a scale ranging from 0 (No pain) to 10 (Extreme pain). In the IPQ , a reconAlexithymia was assessed using the Italian version of the 20-Item Toronto Alexithymia Scale (TAS-20) . The TASThe Italian version of the Hospital Anxiety and Depression Scale (HADS)  was usedThe Italian version of the Short-Form 36 Health Survey (SF-36) was used . It consNormal distribution was assessed following the criteria of absolute skewness (Sk) and kurtosis (K) values lower than 3.0 and 8.0, respectively . Based op-value < 0.05). Collinearity was assessed using the statistical factors of tolerance and Variance Inflation Factor (VIF).Two hierarchical multiple regression analyses were used to investigate whether alexithymia was a significant contributing factor for the explanation of the HRQoL in FM patients, using the Physical and Mental Components scores of the SF-36 as outcome variables. Stepwise method was used for variables inclusion of potentially confounding and competing predictors. To avoid unnecessary reductions in statistical power, confounding  and competing  predictors’ variables were included in the regression models only when they were significantly correlated with the outcome variables . The mediation analyses were conducted using the PROCESS macro , a compuTable 1. Patients had a mean (SD) age of 51 (10) years and the majority of them had a secondary school degree at least. On average, the patients had chronic pain from 8 years and the mean PI was higher than 7. The result of the IPQ showed that patients reported the highest scores in the affective pain dimension (IPQ-A).Data on the socio-demographic and pain variables are reported in Table 2. A total of 26% of the sample reported the presence of alexithymic trait at a clinical level (53 patients) and another 26% showed this trait at a subclinical level (54 patients). More than 60% of the patients reported a clinically relevant level of depressive/anxiety symptoms.Data regarding alexithymia and psychological distress are presented in Table 2. Patients reported very low mean values in all the subscales of the SF-36, suggesting the presence of a poor QoL in both its physical and mental components.Data regarding the HRQoL are summarized in Table 3). Age, educational level, and pain duration were not significantly correlated with the physical and mental components of the SF-36. Pain was negatively and significantly correlated with both the SF-36_PC (p < 0.001) and the SF-36_MC (p < 0.001): the higher the PI, the lower the HRQoL. Statistically significant negative correlations were found between HADS-D and HADS-A, and both the physical and the mental components of the SF-36 , showing that higher psychological distress symptoms were correlated with a worse HRQoL. Regarding alexithymia, the DIF and DDF subscales of the TAS-20 were significantly correlated with both the SF-36_PC  and the SF-36_MC (both p < 0.001), suggesting that higher difficulty identifying and describing feelings were associated with a worse HRQoL. No significant correlations emerged between HRQoL and the EOT subscale of the TAS-20.In order to verify possible relationships between clinical and psychological variables, and HRQoL, correlation analyses were performed  and the HADS-A  scales, suggesting that higher level of alexithymia were associated with a higher psychological distress. Both alexithymia  and psychological distress  were significantly correlated with the VAS score: the higher the PI, the higher the alexithymia and psychological distress symptoms.Higher alexithymia scores were also significantly correlated with higher scores on the HADS-D ] were entered in the second block with the stepwise method.Table 4. In the first model, when only alexithymia features were entered into the analysis, the difficulty identifying feeling (DIF) subscale of the TAS-20 significantly predicted the criterion . However, alexithymia ceased to be a predictive factor when depression was entered into the analysis, in the third model. The final model (model 3) explained a significant amount (45%) of the variance of the SF-36_PC  and PI appeared to be the strongest contributor , followed by depression .The regression analysis regarding the Physical Component is reported in Table 5. When only alexithymia features were entered into the analysis (model 1), the difficulty identifying feeling (DIF) subscale of the TAS-20 significantly predicted the criterion , with a 36% of the variance of the SF-36_MC explained. However, differently from the previous regression, alexithymia continued to be a predictive factor when competing predictors were entered into the analysis. The final model (model 4) explained a significant portion (61%) of the variance of the SF-36_MC . Anxiety symptoms , depressive symptoms  and alexithymia  followed by PI  were the factors that significantly predicted the SF-36_MC score.The regression analysis regarding the Mental Component is reported in To deepen the results of the multiple regression analyses, a mediation analysis was conducted to test the relationship between alexithymia and the patients’ HRQoL mediated by depressive symptoms. On the basis of the results of the regression analyses, the DIF subscale was used.Figure 1A), the standardized regression coefficient between DIF and depressive symptoms was statistically significant (p < 0.001), as was the standardized regression coefficient between depressive symptoms and SF-36_PC (p < 0.001). The standardized indirect effect was (0.52)(-0.46) = -0.24. We tested the significance of this indirect effect using bootstrapping procedures. The bootstrapped unstandardized indirect effect was -0.52, and the 95% CI ranged from -0.73 to -0.35. Thus, the results confirm that, even if DIF did not have a direct effect on the SF-36_PC , it had a significant indirect effect (κ2 = 0.22) through depressive symptoms.Regarding the Physical component , the standardized regression coefficient between depressive symptoms and SF-36_MC was statistically significant (p < 0.001). The standardized indirect effect was (0.52)(-0.46) = -0.24. The bootstrapped unstandardized indirect effect was -0.66, and the 95% CI ranged from -0.90 to -0.48. Thus, in addition to confirm the presence of a statistically significant direct effect , the results confirm that the difficulty identifying feeling subcomponent of alexithymia had a significant indirect effect on the Mental Component of the SF-36 (κ2 = 0.25) through depressive symptoms.Concerning the Mental Component , its relative stability has been demonstrated not only in patients with major depression, but also in patients with functional gastrointestinal disorders . It can Some main limitations have to be taken into account while considering the present study. Only female patients were evaluated and we did not include any control groups. Further studies comparing FM to other chronic pain pathologies should therefore be carried out. What is more, while this study contributes with important information regarding how alexithymia and depression may interact in FM, the cross-sectional nature of the study does not allow proving causal relationships. Future researches should address emotional deficits in this chronic pain pathology through longitudinal studies, assessing the variation of these co-occurring symptoms along the disease progression.per se seems to directly contribute to worsen the impact that this chronic pain pathology has on the patients’ quality of life, especially regarding the psychosocial functioning. Taken together these results have an important implication for the treatment of FM patients. As recently reported, indeed, treatment strategies have on average only modest results in FM patients, calling for a more individualized management strategy (The results of the present study suggest the presence of both a direct and an indirect effect of alexithymia on the HRQoL in patients with FM. Indeed, even though the concomitant presence of depressive symptoms is responsible of an indirect effect, alexithymia strategy . The prestrategy , furtherstrategy . Accordistrategy . Furtherstrategy . Similarstrategy . These dThis study was carried out in accordance with the recommendations of ‘Comitato Etico Interaziendale A.O.U. Città della Salute e della Scienza di Torino – A.O. Ordine Mauriziano – A.S.L. Città di Torino’ 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 ‘Comitato Etico Interaziendale A.O.U. Città della Salute e della Scienza di Torino – A.O. Ordine Mauriziano – A.S.L. Città di Torino.’VT, LC, and GG were responsible for the conception and design of the study. AG, AR, FC, and EF were responsible for data collection and for clinical evaluations. VT and MDT were responsible for data analysis. LC and GG contributed to the interpretation of data. VT and MDT wrote the article, which was critically revised by all the other authors. All authors have 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.


Aim. Headache is one of the most common diseases associated with Temporomandibular Disorders (TMDs). The aim of this study was to evaluate, retrospectively, if headache influences TMD's symptoms. Material and Methods. A total sample of 1198 consecutive TMD patients was selected. After a neurological examination, a diagnosis of headache, according to the latest edition of the International Classification of Headache Disorders, was performed in 625 subjects. Patients were divided into two groups based on presence/absence of headache: Group with Headache (GwH) and Group without Headache (GwoH). Descriptive statistics and Chi-square index were performed. Results. Sociodemographic  and functional factors, occlusion , and familiar pain did not show a statistically significant correlation in either group. Intensity and frequency of neck pain, arthralgia of TMJ, and myalgia showed higher correlation values in GwH. Conclusion. This study is consistent with previous literature in showing a close relationship between headache and TMD. All data underlines that headache makes pain parameters more intense and frequent. Therefore, an early and multidisciplinary treatment of TMDs should be performed in order to avoid the overlay of painful events that could result in pain chronicity. Temporomandibular Disorders (TMDs) involve alterations of the temporomandibular joint (TMJ), masticatory muscles, and related structures. Many of the clinical and instrumental aspects of these disorders overlap with other medical disciplines like otology, neurology, psychiatry, and others . HeadachPatients with headache and TMDs reported significantly higher levels of pain and disability compared to patients with only TMDs , 10.The aim of this study was to evaluate if headache influences TMD's symptoms; to investigate the research purpose two homogeneous groups of TMD patients with and without headache were analyzed.To address the research purpose, the authors designed and implemented a retrospective cohort study, conducted at the Department of Oral and Maxillofacial Sciences, at “Sapienza” University of Rome, and approved by the institution review board (ref. number 2086/15).The study sample was composed of a population derived from patients presenting at the University's Department for TMDs management in an interval of time between January 2011 and December 2013, according to the inclusion and exclusion criteria.Subjects eligible for study inclusion had TMD diagnosis, based on Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) , and proPatients were excluded from enrollment to the study, if they had an uncontrolled systemic disease, missing medical records, a history of mental disorders, or refused to enroll to this study.Subjects with coexisting/history of drug administration, physiotherapy, and splint therapy for previous headache treatment were excluded from the study.A total sample of 1198 TMD patients was selected. Presence of headache was analyzed using both clinical parameters recorded on patient's medical charts and answers given by patient on the DC/TMD Symptom Questionnaire.Headache was found in 894 (75%) patients while in 304 (25%) was excluded.In order to differentiate headache and perform a correct diagnosis to exclude false positives, all patients positive for headache were invited to undergo a neurological visit with a neurologist specialized in the diagnosis of primary headache according to the latest edition of the International Classification of Headache Disorders (ICDH-III) .After the neurological visit, in accord with ICHD-III, a diagnosis of headache was performed in 625 patients.Two hundred and sixty-nine patients were excluded from the study: in particular, 191 subjects did not undergo the neurological examination and 78 were found to be affected from other neurological diseases, such as atypical facial pain and cranial neuralgia.n = 625 (67.3% of TMD sample).Group with Headache (GwH), composed of n = 304 (32.7% of TMD sample).Group without Headache (GwoH), composed of The total sample of TMD patients composed by 929  was divided into two groups based on presence/absence of headache in TMDs:Sociodemographic factors .Types of pain .Functional aspects .Occlusion .Diagnostics  with Reduction (R), Subluxation, DD with Reduction (R) and intermittent Mouth Opening Limitation (MOL), DD without R with MOL, DD without R without MOL, and degenerative joint disease).Based on the analysis of the medical charts, five categories of variables were considered:Age was evaluated through a qualitative scale with the following subdivisions: 0–15 childhood, 16–25 adolescents/young adults, 26–40 adults, 41–50 middle-aged adults, 51–60 mature/older adults, 61–70 seniors, and 71+ elders.The type of pain was evaluated for each individual patient, considering anatomical position and intensity.Pain intensity  was evaluated utilizing the Verbal Numeric Scale (VNS) , which uFamiliar pain was identified as the pain that prompted the patient to the gnathological visit.Emotional strain was assessed using the DC self-evaluation questionnaire system and investigating the presence/absence of stress time beyond the norm during the previous six months.Maximum spontaneous mouth opening was evaluated using numeric values in millimeters (mm) according to the parameters set by the DC/TMD; then the value obtained for each patient was converted into a qualitative functional measurement, using the following division into classes: 0–20 (severe restriction), 21–30 (limited), 31–40 (mild limitation), 41–50 , and 50+ (laxity).Presence/absence of parafunctional habits was assessed through the patient's medical history and a clinical evaluation of the morphological-functional state of the skeletal muscles and of the dental-periodontal tissues.α = 0.05.The prevalence of headache in patients with TMDs was analyzed proportionally among subjects from the Total Dysfunctional Sample (TDS) who tested positive to cephalic pain for the entire period considered (2011–2013). Confidence intervals were set at 95% to obtain a precise estimate of headache prevalence in the sample. The Chi-square index was performed to evaluate the significance of statistical correlation among the variables considered, with a level of statistical significance Sociodemographic  and functional factors, occlusion , and familiar pain did not show a statistically significant correlation in either group.N = 625, CI95%: 64.3%–70.3%). In GwH, pain score was 70 ± 24.4 VNS and 78% of patients  showed VNS values higher than 50. According to the ICHD-III, the types of headache diagnosed by the neurologist were in order of decreasing frequency: Migraine without Aura (MwoA), Episodic Tension Type Headache (ETTH), Chronic Migraine (CM), Chronic Tension Type Headache (CTTH), Migraine with Aura (MwA), Headache attributed to TMD (TMD Headache), and Headache attributed to disorder of Neck (Neck Headache) (N = 182) and 41–50 (N = 166). Patients of 16–25 (N = 73) and 51–60 (N = 69) were the most represented in GwoH. All variables considered showed higher values in GwH, while absence of pain was more frequent in GwoH  . Statisteadache)  and in teadache) . In GwH, in GwoH .X-squared value = 24.3216) and between intensity of same-side joint and cephalic pain . The following associations were found to be statistically significant: intensity of muscular pain and ipsilateral headache; neck pain and headache  and parafunctional habits  showed higher values in GwH, with a correlation between headache and parafunctions   .X2 value = 5.1456, df = 1, χ1,0.952 = 3.84). Other diseases demonstrated lower or insignificant correlation , in agreement with current literature.Headache appeared to be the most common symptom of diseases accompanying TMD . CiancagN = 187, Cl95%: 26.3%–3.5%) and 24.5% , respectively.Other studies –18 showeIn the dysfunctional Group with Headache (GwH), the peak age group was “30–40” . These rThe different behavior between GwH and GwoH could be explained by the fact that headache determines an increased central sensitization to pain and an exacerbation of pain symptoms in the craniocervical-mandibular joint, thus motivating patients to seek treatment for previously existing gnathologic problems .Central sensitization is characterized by pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation , 21.In addition, absence of severely painful symptoms might induce patients to underestimate dysfunctional problems, which could become discernible only in the chronic phase, explaining the second age peak (40–60 years) in GwoH.95%: 75%–81%) of dysfunctional patients in our study. These results suggest that when patients report a severe headache, a clinical assessment of the morphofunctional state of temporomandibular joints and masticatory muscles should be performed in order to exclude the presence of TMDs. Our research found that painful pathologies of the craniofacial region are more frequent and intense in patients who suffer simultaneously from headache. Compared to GwoH, the increase in pain in GwH could also be explained by the greater central and peripheral nervous sensitivity that characterizes patients with headache. In dysfunctional patients, there is a significant association between presence of painful sites during palpation in areas innervated by the trigeminal nerve and headache frequency [Several studies , 23 showrequency –27. Accorequency , differerequency , 30. Thirequency .95%: 12.3%–23.9%) and 21.7% (Cl95%: 19.7%–23.7%)   . A corre42.7842) . Indepen42.7842) . Data thx-square = 27.4131 versus x-square values = 59.1496)  . In partThis study is consistent with previous literature in showing a close relationship between headache and TMD. Data underlines that headache makes pain parameters more intense and frequent, complicating dysfunctional diseases both in the diagnostic phase and in treatment. Therefore, it is desirable to perform an early and multidisciplinary treatment of TMDs in order to avoid the overlay of painful events that could result in pain chronicity.


Multimodal analgesia is an essential component of an enhanced recovery pathway (ERP). An ERP that includes the use of single-injection intrathecal analgesia (IA) has been shown to decrease morbidity and cost and shorten length of stay (LOS). Limited data exist on safety, feasibility, and the optimal IA regimen. Our objective was to characterize the efficacy, safety, and feasibility of IA within an ERP in a cohort of colorectal surgical patients.  We performed a retrospective review of all consecutive patients aged ≥ 18 years who underwent open or minimally invasive colorectal surgery from October 2012 to December 2013. All patients were enrolled in an institutional ERP that included the use of single-injection IA. Demographics, anesthetic management, efficacy (pain scores and opiate consumption), postoperative ileus (POI), adverse effects, and LOS are reported.  601 patients were identified. The majority received opioid-only IA (91%) rather than a multimodal regimen. Median LOS was 3 days. Overall rate of ileus was 16%. Median pain scores at 4, 8, 16, 24, and 48 hours were 3, 2, 3, 4, and 3, respectively. There was no difference in postoperative pain scores, LOS, or POI based on intrathecal medication or dose received. Overall, development of respiratory depression (0.2%) or pruritus (1.2%) was rare. One patient required blood patch for postdural headache. NCT03411109. Intrathecal analgesia is safe, feasible, and efficacious in the setting of ERP for colorectal surgery. All regimens and doses achieved a short LOS, low pain scores, and a low incidence of POI. This trial is registered with Clinicaltrails.gov  Enhanced recovery pathways have been shown to decrease morbidity, length of hospital stay, and costs in colorectal surgery –6. TheseLong-acting opioids are considered the cornerstone of single-injection IA for postoperative pain. While morphine has been considered the gold standard opioid for IA, recent national drug shortages have limited its availability. Hydromorphone is an alternative long-acting opioid that has grown in popularity, particularly for chronic pain. Its role in acute postoperative pain is less clear. Limited data exist on the safety, efficacy, and optimal IA medication regimen in the setting of an ERP including open and laparoscopic surgery. Therefore, we aimed to describe the efficacy and safety of IA, including intrathecal hydromorphone, in a cohort of colon and rectal surgical patients in a standardized ERP program.Institutional review board approval was obtained (ID # 13-007936). We retrospectively identified all colorectal procedures from October 2012 through December 2013 in which patients received single-injection IA as part of a multimodal analgesic strategy for ERP. Patients were identified from the prospectively-defined Mayo Clinic Colorectal Surgery Database. Inclusion criteria were age ≥ 18 years, undergoing an elective colorectal operation , enrollment into the institutional perioperative ERP, and receiving preoperative single-injection IA. Patients undergoing emergent operations or who refused research authorization were excluded.Our institution's enhanced recovery pathway has previously been described . The anaAll patients were monitored according to institutional guidelines outlined in a standardized intrathecal for analgesia order set. This consists of continuous pulse oximetry and nursing assessments every hour for first 12 hours, then every 2 hours for next 12 hours, then every four hours in a general care setting. Intensive care unit monitoring was not routinely required .Demographic data (age and sex) and operative details including anesthetic/analgesic management (dosage and pain scores) were collected from the anesthetic record. Short-term postoperative outcomes including verbal rating pain scores at 4, 8, 12, 24, and 48 hours after PACU discharge, postoperative opiate consumption ), postoperative ileus , and length of stay  were collected from the colorectal surgical database. Adverse effects related to neuraxial opiate administration were recorded, specifically searching for the administration of naloxone as a surrogate metric for respiratory depression and nalbuphine as a surrogate for pruritus within 24 hours of surgery. Finally, presence of postdural puncture headache and requirement for a blood patch were collected using a free-text search of the medical record.F-test or nonparametric Kruskal-Wallis test. For categorical variables, the chi-square or Fisher's exact test were used. A p value of 0.05 was considered statistically significant. All analyses were performed used SAS.Continuous variables were summarized with mean and standard deviation (SD) or median and interquartile range (IQR). Categorical variables were summarized with frequencies and percentages. The comparison of continuous variables between groups was performed using the one-way ANOVA n=547, 91%) received IA-O. There was no statistically significant difference observed in length of stay (LOS) when comparing IA-O or IA-L. Pain scores were also similar; however, the median 48 hour postoperative maximal pain score reported was higher in those receiving IA-L . Furthermore, a greater proportion of those patients receiving IA-O utilized zero OMEs compared to IA-L   .n=427, 71%). There was no difference in the reported pain scores at all measured intervals. However, the total oral morphine equivalents (OME) utilized were greater in those patients with higher dose IA, specifically those receiving 76–100 mcg or >100 mcg (p=0.01). When eliminating those patients who received zero OMEs, there was no difference in OME received between the dose ranges (p=0.14). Fifty-five patients received >200 OMEs; when reviewing these patients, the majority (n=42) had either an open operation with midline incision or a hand-assisted approach.Patients were grouped into one of four hydromorphone dose ranges: <50 mcg, 50–75 mcg, 76–100 mcg, and >100 mcg . The majp=0.29). The median (IQR) LOS in patients with a LOS greater than 3 days  was 5 days [p < 0.0001).Median (IQR) length of stay (LOS) for the entire cohort was 3 days , 5. LOS s n=258, 3% was 5 Complications of IA were rare. Seven patients (1.2%) were treated with nalbuphine for symptoms of pruritus, and one patient (0.2%) developed respiratory depression requiring administration of naloxone within 24 hours of the administration of IA. One patient (0.2%) required blood patch for postdural puncture headache.Our review of the feasibility, safety, and efficacy of intrathecal analgesia in a high-volume enhanced recovery colorectal surgery program demonstrated that intrathecal analgesia is feasible, safe, and effective across a wide range of opioid dosages. Furthermore, lower dosages of intrathecal opioid appeared to achieve a similar level of pain control.Although the beneficial effects of epidural analgesia have been widely reported –24, the Among the chief concerns often cited with the use of long-acting intrathecal opiates is the risk of respiratory depression. Our report demonstrated this to be a rare event (0.2%). This is less than other contemporary studies, with reported incidences as high as 3% , 18, 25.Intrathecal analgesia within an ERP is performed to provide an additional pain control mechanism within a multimodal pathway that also includes acetaminophen (paracetamol) and NSAIDs. Larson et al. previously reported our experience that pathway compliance, low postoperative oral morphine equivalent (OME) usage (<30 mg), and high surgeon volume (>100 cases per year) were associated with discharge from the hospital within 48 hours . In thisConsistent with best practices for anesthesiology and pharmacists, we generally feel that the lowest effective dose should typically be employed. Though limited data are available on the use of intrathecal hydromorphone for acute postoperative pain, a recent prospective comparison of spinal hydromorphone and morphine in cesarean section determined that the ED90 of intrathecal hydromorphone was 75 mcg . Our resThe major limitation of this study is that it was conducted as a retrospective cohort study, which in itself presents inherent weaknesses such as incomplete documentation or subjective, biased reporting of outcomes. Though premedication and postoperative analgesic protocols were identical, group assignment to treatment with intrathecal hydromorphone was not randomized or blinded, and the dose of hydromorphone was based on the preference of the attending anesthesiologist. Therefore, potential for selection bias exists with hydromorphone dose and older age and/or type of procedure (open versus MIS). Randomized trials further investigating alternative dosing regimens would limit the inherent associated biases. However, we are still able to report a relatively robust experience and characterize the feasibility, safety, and efficacy of IA.In conclusion, IA is a safe and efficacious mode of analgesia for patients undergoing open and minimally invasive colorectal surgery. All intrathecal regimens and doses were efficacious at achieving a short LOS, low pain scores, and a low incidence of adverse events.


The use of elastomeric devices for ambulatory intravenous pain treatment in Major Ambulatory Surgery (MAS) has been described to improve postoperative pain management. The objective of the study was to describe the first 3 years experience of the use of elastomeric devices for ambulatory intravenous pain treatment in MAS implemented at our site since 2010.Data were retrieved from the medical records for all patients who, between January 2010 and March 2014, underwent surgical procedures at the ambulatory surgical centre at our hospital and were prescribed a home-based continuous intravenous analgesia.Data were retrieved from the medical records of 1128 patients. The most frequent surgical interventions included orthopedic and proctology surgeries. 80 % of patients were discharged home without pain; during the first 48 h after discharge roughly 40 % of subjects were completely free of pain, 50 % reported mild pain (VAS 1 to 3) and 9 % reported higher pain scores (4 and above). Peripheral nerve block was associated to better pain control in the immediate postoperative period. Vomiting in the first 24 h was 4.6 % before introducing haloperidol into the drug schemes, and 2.6 % thereafter. Complications related with the intravenous route required treatment withdrawal in 1.1 % cases. Only 3.5 % of patients returned to the hospital in the first 72 h, mainly for non-pain related reasons. Overall, 99.5 % of patients were satisfied with the treatment received at home.Our initial experience suggest that outpatient multimodal intravenous analgesia in patients undergoing day-case surgery is a feasible alternative in our setting, that allows an effective management of postoperative pain with a small rate of adverse events and complications requiring readmission. Acute postoperative pain (APP) and postoperative nausea and vomiting are the most frequent clinical problems after Major Ambulatory Surgery (MAS). They complicate the recovery, delaying patient discharge or increasing the rate of readmission after discharge. The development of new minimally invasive surgical techniques, the progress in anesthesia and new systems for administration of analgesics have been instrumental to expand the scope of surgical procedures that can be done in MAS settings, including interventions which were previously discarded mainly due to the difficulties to achieve an appropriate control of APP , 2.An appropriate control of pain is a healthcare quality indicator having social and economical implications. However, in US and Canada, where about 70 % of surgical procedures are MAS, 30 % of subjects undergoing ambulatory surgery yet suffer moderate to severe pain in the first 24 h after surgery, despite receiving analgesic treatment [Asociación Española de Cirugía Mayor Ambulatoria- Spanish Association for Major Ambulatory Surgery) subscribed a joint consensus document with other medical-surgical societies, which includes a statement on the need to apply a multidisciplinary, multimodal and individualized approach to surgical pain management [There is general agreement on multimodal analgesia as the most appropriate analgesia in MAS , 5–9. Innagement .Post-operative pain in MAS should be approached already before surgery, with home preoperative medication, and consolidated in the intra-operative period with appropriate anesthesia and analgesia; in particular, nerve blockades, infiltrations and/or instillation of surgical wounds with long lasting local anesthetics have proven to be very effective and should be done systematically . In the The availability of elastomeric infusion systems and pumps for intravenous administration both as continuous infusion and as patient controlled analgesia (PCA) allow stable plasma concentrations of drugs which achieve better control of pain, thus improving efficacy and reducing adverse effects as compared to bolus administration , 17.At our site and in parallel to an early discharge program in MAS, we introduced the use of elastomeric devices for early treatment of postoperative pain in MAS patients on 2008, with the aim to improve postoperative pain management in the first days after surgery. On January 2010 a formal protocol for analgesia in postoperative pain in patients undergoing ambulatory surgery was issued and implemented, which included the use of elastomeric pumps for intravenous analgesia before and after discharge, covering the first 48 to 96 h after surgery depending on the degree of expected pain for each type of surgery. The protocol includes close monitoring by nursing staff for as long as the patient is receiving intravenous treatment.The present report summarizes the three year experience with the protocol for domiciliary intravenous analgesia for the treatment of postoperative pain after major ambulatory surgery, with special emphasis on describing the pain control achieved, and with the aim to identify any specific safety problems that may arise from the application of domiciliary analgesia.th 2014; the requirement for written informed consent was waived by the institutional review board.An early discharge program in MAS with nurse-driven ambulatory follow up was implemented on January 2010. As a part of pain management, the protocol included the use of elastomeric pumps for continuous intravenous analgesia administration during the first 48 to 96 h post-surgery. In February 2014, an observational retrospective study was designed aimed to describe the initial experience regarding the effectiveness and safety of the use of elastomeric pumps for analgesia in this setting. The study protocol was reviewed and approved by an independent ethic’s committee  on March 4Data were retrieved from the medical and nursing records for all patients who, between January 2010 and March 2014, underwent surgical procedures in the CQA  and were prescribed a home-based continuous intravenous analgesia (HBCIA); a semi-structured questionnaire was used for patient follow-up as a part of the protocol activities. Table During this period, five different analgesic schemes were used for HBCIA Table . The choThe elastomeric pumps used were Infusor Folfusor SV 2 (Baxter) which is a portable and disposable non-electronic small volume infuser with nominal flow rate of 2 mL/h and a maximum volume of 130 mL, which allows a slow continuous infusion over 48 h. The pumps were prepared by the hospital Pharmacy Department and delivered to the CQA, where nursing personnel could add to the pump customized antiemetic medications according to the postoperative medical prescriptions.Infusions using HBCIA elastomeric pumps were started either at the anesthetic reanimation room or at the so called unit for adaption to environment, and were maintained for 48 h, regardless of patient discharge to their home. Patients were instructed on general care of venous access and pump care. After 24 h patients received a follow-up call by a nurse, and at 48 h they received a nurse visit at home; in some cases, a new pump was replaced during this visit to prolong HBCIA for additional 24 h or even 48 h (mainly limited to hemorrhoidectomies), as prescribed depending on the intensity of pain. At the end of the prescribed period  the nurse retired the pump and iv access, in addition to reviewing of wounds and dressings, and checked pain and wellbeing. At any time, nurses solved problems derived from the infusion , or stopped the infusion in case of adverse reactions  and derived to the hospital any problem related with the infusion, the drugs infused or any postoperative complication which required medical assessment.Medical and nursing records were reviewed to retrieve demographic data, surgical and anesthetic procedures, and treatments administered before hospital discharge and during the post-surgery period.The main effectiveness assessments were numerical rating scales (0–10) for post-operative pain which were routinely assessed by the semi-structured form used by nurses for patient follow-up, as a part of the protocol activities, at entry and discharge of each care unit, and also once daily during ambulatory care.Also, safety information was obtained from the routine assessments performed before discharge and after during ambulatory visits. The semi-structured forms included assessments for presence of nausea, vomiting, somnolence and pruritus, need for analgesic rescue medication, incidences with the infusion system and patient satisfaction (satisfied or not satisfied). Any further hospital admissions or visits to emergency ward were retrieved from the hospital admission records.Quantitative variables were described and are presented as mean ± standard deviation, and qualitative variables with number and percentages, considering the different transitions of care from reanimation to the unit for adaption to environment, and then daily for the home care period, either on the phone or during a home visit. The numerical pain rating scale was categorized as no pain (0), mild pain (1–3), moderate pain (4–6) and intense pain (7–10).From January 2010 to March 2014, 1135 patients underwent major outpatient surgery at CQA who were prescribed home-based analgesia with an elastomeric pump. Of these, 5 patients did not finally receive treatment with elastomeric pumps: 4 because they were admitted to regular hospitalization due to nausea, sickness or pain, during the immediate postoperative period, and 1 due to technical problems with the pump which precluded its use. Two more patients were excluded from description because no nursing visits were done in the first two days due to logistic problems (snow storm). Table Table The type of multimodal analgesia used in the elastomeric pumps is described in Table According to the routine pain assessments, most patients were free of pain immediately after surgery, and only 11.3 % presented moderate or intense pain (pain scores ≥ 4). As expected, knee and shoulder surgery were the most painful interventions with 22.3 % and 25.2 % of patients presenting at least moderate pain, respectively. Nearly 80 % of patients were discharged home without pain, and around 40 % referred to be completely free of pain at home after 24 and 48 h from surgery . 15.4 % of patients used rescue medication with oral tramadol at some time on top of their HBICA.Adverse reactions were infrequent. Intravenous treatment was retired in 5 cases due to emesis and in 8 cases due to other adverse reactions . Complications related with the intravenous route included extravasation in 15 (1.3 %) patients and phlebitis in 4 patients. In 12 (1.1 %) cases the route had to be replaced or retired due to technical problems. During the first 72 h after surgery, 40 patients (3.5 %) returned to the hospital. Figure Our series describes the experience of more than 3 years with an early discharge program in MAS, in which we introduced the use of elastomeric devices for early treatment of postoperative pain that was extended after discharge, including home-based continuous intravenous analgesia.In our 1128 patient series, we have observed that pain control while at the surgical centre allowed that 80 % of patients were discharged home with no pain, and that during the first 48 h after discharge, roughly 90 % of subjects were either completely free of pain or reported mild pain scores. However, yet a 9 % reported pain scores of 4 and above.Most patients received a 48 h infusion and then were switched to oral route; for these, no further pain assessments were available since they were considered completed as regards to special follow-up. Only patients undergoing surgeries considered to be very painful received extended infusions and were followed over 72 or even 96 h; this may be the reason why our data show worse pain control rates at 72 h, with a proportion of patients with scores ≥ 4 up to 14 %.We consider that our results may be regarded as good, as compared to similar series in both inpatient and outpatient setting. In a case series from the Netherlands, moderate to severe postoperative pain was present in 41 % of hospitalized patients on the first day of surgery, and in 15 % of patients on the 4th day . In the All the therapeutic schemes in the elastomeric pumps that were used during the studied period contained tramadol, and almost all (> 97 %) combined both tramadol and dexketoprofen. Routine use of tramadol has been controversial, since nausea and vomiting have been described in up to 40 % of treated patients in some series , 23. RawRegarding other clinical outcomes, it is remarkable that we observed a low incidence of complications related to the intravenous route, like extravasation or phlebitis, and the need to replace the venous access or to withdraw the intravenous treatment occurred only in 1.1 % of cases . Also, iOne of the key aspects of our outpatient program is the domiciliary patient follow-up, combining telephonic and in-person nursing care in the early postoperative period. The program uptake was remarkably well accepted by medical and nursing staff , but alsThere are a number of limitations to our report. First, this is a report of our clinical experience. Data has been collected retrospectively from clinical charts and simple forms that were designed for clinical purposes during the ambulatory follow at the time of program implementation, and thus the information has not been collected in a standardized and prospective way intended for research purposes. Thus the results reported should be considered within this observational perspective, especially as regards to effectiveness. Also, it has been previously reported that several risk factors can be identified to predict the requirement of prolonged stay in ambulatory surgery . Since tWe present aggregated data for many different surgeries that are known to have quite different pain management requirements and characteristics, and report joint results for a number of different drug preparations. Besides, the type of drug combinations used along the program implementation have been slightly modified in time, so that i. ex. antiemetic drugs, mainly haloperidol, were added to the elastomeric preparations after first year. However, the availability of a number of combinations allowed personalized choices according to each subject characteristics, considering allergies, comorbidities, risks for adverse events and type of surgery. Likely, a reasonable degree of flexibility may be useful to maintain a low rate of complications and improve clinical results.Our data suggest that an approach based on extending the intravenous multimodal analgesia after discharge has proven to be feasible and appropriate in a wide series of patients in our setting, and in many surgical procedures, and has proven safe and easy to apply within the parameters defined by our program. Whether this approach may be translated to other settings is uncertain, since the availability of resources, the relatively close proximity of the geographical area to cover, and the easiness of arrangements for home visits after discharge may be difficult to reproduce in other geographies and health system models. We have observed an effective management of postoperative pain with an acceptable rate of adverse events and complications, and the process has been feasible and well accepted by all involved parties. We think that our experience may be useful to other groups who may be considering strategies aimed to enhance patient access to surgical procedures, and since the objectives of the program have been achieved, these results reinforce its continuation and suggest the convenience to consider the extension of the model to other types of surgeries.


To identify factors, available at the time of trauma admission, associated with the development of chronic pain to allow testing of preventive approaches.  In a retrospective observational cohort study, we included all patients ≥ 18 years old admitted for injury in 57 adult trauma centers in the province of Quebec (Canada) between 2004 and 2014. Chronic pain was defined as follows: treated in a chronic pain clinic, diagnosed with chronic pain, or received at least 2 prescriptions of chronic pain medications 3 to 12 months postinjury.  A total of 95,134 patients were retained for analysis. Mean age was 59.8 years (±21.7), and 52% were men. The causes of trauma were falls (63%) and motor vehicle accidents (22%). We identified 14,518 patients  who developed chronic pain. After controlling for confounding factors, the variables associated with chronic pain were spinal cord injury , disc-vertebra trauma , history of alcoholism , history of anxiety , history of depression , and being female . The area under the receiving operating characteristic curve derived from the model was 0.80.  We identified risk factors present on hospital admission that can predict trauma patients who will develop chronic pain. These factors should be prospectively validated. Traumatic injury accounts for approximately 37 million emergency department visits each year in the US . For manThe prevalence of posttraumatic chronic pain varies greatly between and within injury types: from 22 to 93% in orthopedic trauma , 26–96% Several studies have identified risk factors of chronic pain development in trauma patients , 7. DemoIf used during the acute pain phase, some therapeutic strategies  may help prevent the development of chronic pain . As primThe main objective of the present study was to identify factors, available at hospital admission, associated with the development of chronic pain for trauma patients and to develop a predictive model.A retrospective multicenter cohort study was conducted using three government population databases. All patients of 18 years and older admitted for injury to any one of 57 adult trauma centers  in the province of Quebec (Canada) between 2004 and 2014 were included in the study. Patients who died or with a follow-up period less than 1 year and those with multiple trauma episodes (difficult to identify which trauma episode was associated with chronic pain) were excluded.Quebec Trauma Registry was developed in 1993 and involves mandatory data collection for patients admitted to any provincial trauma center according to the following inclusion criteria: death following injury, hospital stay > 2 days, intensive care unit admission, or transfer from another hospital. Medical archivists extract registry data from patients' medical files, using standardized coding protocols. Anatomic injuries are coded with the Abbreviated Injury Scale (AIS) according to guidelines published by the Association for the Advancement of Automotive Medicine [The Medicine . The regMED-ECHO  is a medico administrative database managed by the Quebec Ministry of Health. It contains information on principal and secondary diagnoses and medical interventions for all hospitalizations in the province of Quebec. For each included patient, access to MED-ECHO information was granted for a time period ranging from 1 year before to 8 years after the target injury.RAMQ medical consultations and medication database of the Régie de l'Assurance Maladie du Québec is an administrative database maintained by the Quebec Ministry of Health and contains diagnostic information and specific codes for chronic pain visits for all medical consultations in the province of Quebec. It also contains information on all medication prescriptions filled for Quebec residents covered by the Quebec prescription drug insurance plan, which represent approximately 50% of all included individuals. The RAMQ database provided information on included patients for the same time period as for the MED-ECHO database.The The three databases were linked using a unique anonymous identification number provided by the “Régie de l'assurance maladie du Québec.” Access to these databases required the ethic approval of the “Commission d'accès à l'information du Québec” (CAI) and the “Responsable de l'accès à l'information et de la protection des renseignements personnels de la RAMQ” (RAI-RAMQ). The CAI and the RAI-RAMQ approved our study for cases registered in the Quebec Trauma Registry between 2004 and 2014.Chronic pain (pain experienced for at least 3 months) patients were identified using any of the following 3 criteria: (1) Patients who were referred to a specialized chronic pain clinic . (2) Patients diagnosed with chronic pain  during their entire follow-up period (up to 8 years after injury). We used the entire follow-up (from 3 months to 8 years after injury) for these chronic pain criteria since access to specialized chronic pain clinics can extend for years. (3) Patients who filled at least 2 prescriptions of opioids or at least 1 prescription of chronic pain medication  , injury severity score (ISS), abbreviated injury scale (AIS), emergency department (ED) stay duration, and history of alcoholism, depression, or anxiety 1 year prior to target injury. A score greater than 15 on the ISS was used to define major trauma or polytrauma . The firt-tests) to compare the characteristics of the included patients versus those who were excluded (died or had a follow-up less than 1 year). We randomly selected two-thirds of cases to generate a derivation sample used to create a model to predict chronic pain and the last third was used as a validation sample [t-tests) to compare the characteristics of the derivation and the validation samples. Since small differences can result in a statistically significant test in very large samples, Cohen's effect sizes are presented instead of p values. Small, medium, and large effect sizes for Chi-square are 0.1, 0.3, and 0.5, respectively, and for the t-test statistic, 0.2, 0.5, and 0.8, respectively [We used univariate statistics  were selected for multivariate analysis. We used a multivariate logistic regression analysis with backward stepwise procedure to develop the model on the derivation sample using chronic pain development as the dependent variable. Performance of the derivation sample model was assessed using Nagelkerke's On the validation sample, the logistic regression equation (derived on the derivation sample) was used to predict chronic pain. Performance and discrimination were also evaluated using the Brier score and the c-statistic, respectively.Alpha levels were set at 0.05 and all analyses were performed using SPSS version 23 . Results are reported according to the “Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis” (TRIPOD) Statement .The Québec Trauma Registry included a total of 151,189 adult patients admitted for an injury between January 1, 2004, and March 31, 2014. Of these patients, 11% were excluded for having more than one injury episode, 6.3% because they met the chronic pain criteria during the year preceding their target injury episode, and 19.8% because they died or had a follow-up shorter than a year. A total of 95,134 subjects to create the derivation and validation sample were retained .  Table The mean age of the selected sample was 59.8 years (SD ± 21.7), almost half (48.1%) were female, and the mean follow-up duration was 4.8 years (SD ± 2.4). The most common mechanism of injury was falls (63%), 17% had major trauma, and the average time spent in the ED was 17 hours. In the whole sample, 14,518 patients  developed chronic pain during the follow-up period according to our three criteria: 92% of the chronic pain patients were identified through chronic pain medication consumption, 7% had a chronic pain clinic consultation code, and 4% were diagnosed with chronic pain when subsequently hospitalized.Univariate comparisons of patients' characteristics for the derivation and the validation samples are presented in N = 62,669) are presented in p value calculated on the derivation sample was 0.01, the Nagelkerke's percentage of variance explained was 0.28, the Brier score was 0.11, and area under the ROC curve was 0.80 (95% CI: 0.79–0.81). Except for calibration (Hosmer–Lemeshow), performance (Nagelkerke's and Brier score) and discrimination (area under the ROC curve) values are within the range of an informative model.Because collinearity was strong between insurance status and age , age was removed from the multivariate analysis. Results of the multivariate logistic regression analysis using the derivation sample , the Brier score remained at 0.11 and the area under the ROC curve was estimated at 0.80 (95% CI: 0.80–0.81) which is consistent with strong discrimination [When the logistic regression equation using the same predictors was applied to the validation sample . Except for loss of consciousness, which was no longer significant, the same set of predictors with approximately the same odds ratios was associated with the development of chronic pain.In a sensitivity analysis on the derivation sample, we performed the same stepwise logistic regression using only patients covered by the Quebec prescription drug insurance plan , injury characteristics, and history of alcoholism, anxiety, or depression have all previously been identified as predictors of chronic pain , 19–22. However, our study was done on a very large sample size  from the Quebec Trauma Registry, a reliable government supervised database. For example, inclusion in the Quebec Trauma Registry is mandatory; it uses standardized coding protocols and is subject to periodic validation. Our study is also the first to focus on risk factors present on hospital admission. Furthermore, we validated our predictive model on a large distinct sample . This predictive model could allow for the prompt screening of the trauma population at risk of developing chronic pain, early testing, and implementation of preventive approaches.The discrimination power of our model is good  and is higher than a recently published study predicting chronic pain development in patients with acute low back pain . HoweverThe prevalence of chronic pain development found in the present study (15.3%) is lower than that observed in two major reviews in trauma populations (from 22% to 96%) . The chrThis study has other limitations. The majority (92%) of our chronic pain patients were identified through the use of the chronic pain medication criteria. Since almost half of our trauma population were not covered by the Quebec prescription drug insurance plan, the prevalence of chronic pain development was likely underestimated, even in the presence of the other two criteria.The definition of chronic pain in our study may introduce other biases in the estimation of chronic pain prevalence and could also affect our risk factor modelling. Since we used the following proxy—filling at least 2 pain medication prescriptions within 3 to 12 months after the target injury—to define chronic pain development, we cannot exclude that some patients filled their prescriptions but did not consume any medication, or were taking pain medication for a subsequent injury/health problem or even became addicted to the pain medication. The retrospective design of this study limited our choice of chronic pain development predictors to variables included in the Quebec Trauma Registry. For example, pain intensity level on hospital admission, which has been shown as a consistent predictor of chronic pain in a trauma population, was not available in the Quebec Trauma Registry. Finally, history of alcoholism, depression, and anxiety was limited to the year preceding the target injury. Prospective studies are needed to evaluate and improve the ability of our model to predict chronic pain development from predictors that are available at hospital admission.Despite the relatively low incidence of chronic pain in our injury cohort, we identified risk factors present on hospital admission that can reliably predict trauma patients who will develop chronic pain. These factors should be prospectively validated. Hospital admission screening of the trauma population at risk of developing chronic pain could allow for early testing and implementation of preventive approaches.


The indications and clinical necessity for routine hardware removal after treating ankle or distal tibia fracture with open reduction and internal fixation are disputed even when hardware-related pain is insignificant. Thus, we determined the clinical effects of routine hardware removal irrespective of the degree of hardware-related pain, especially in the perspective of patients' daily activities. This study was conducted on 80 consecutive cases (78 patients) treated by surgery and hardware removal after bony union. There were 56 ankle and 24 distal tibia fractures. The hardware-related pain, ankle joint stiffness, discomfort on ambulation, and patient satisfaction were evaluated before and at least 6 months after hardware removal. Pain score before hardware removal was 3.4 (range 0 to 6) and decreased to 1.3 (range 0 to 6) after removal. 58 (72.5%) patients experienced improved ankle stiffness and 65 (81.3%) less discomfort while walking on uneven ground and 63 (80.8%) patients were satisfied with hardware removal. These results suggest that routine hardware removal after ankle or distal tibia fracture could ameliorate hardware-related pain and improves daily activities and patient satisfaction even when the hardware-related pain is minimal. Displaced ankle and distal tibia fractures are among the most common fractures of the extremities and are often treated by open reduction and internal fixation (ORIF) , 2. Howe in situ and are unconvinced of clinically significant adverse effects, but this report described only surgeons' opinions and practice patterns and did not consider the topic from the patient's perspective [Pain from soft tissue irritation when normal activities resume after fracture healing is typical indication for removing implants from adults . The conspective .The incidence of late pain at fracture hardware sites and rate of hardware removal for late pain for ankle or distal tibia fractures are also not well documented. Moreover, little information is available on the relative merits of hardware removal after ORIF, and almost no studies have considered the change of patients' functional status related to daily activities after routine hardware removal , 7. TherInstitutional Review Board approval was obtained for this study and informed consent was obtained from all patients involved. We had used some implants which included 3.5 mm cortical screws, 4.0 mm partial-threaded cannulated screws, one-third tubular plates, and/or locking compression plates  for treating all these fractures. This study included patients who already had been initially treated by ORIF at our institution from July 2006 to July 2010 and enrolled consecutive 80 ankle or distal tibial fractures that underwent hardware removal after fracture bony union. Patients with intra-articular distal tibia fractures were excluded because intra-articular joint pain could confound the results.Hardware removal was routinely recommended only after a noneventful course and radiographically confirmed bony union, usually about 1 year after surgery, even when hardware-related pain or ill-defined ankle discomfort was minimal. Hardware was not removed from the patients with age of more than 65 years considering the life expectancy. Patients were followed up for at least 6 months after removal.Patients were interviewed at the clinic by one of the authors (JIK) who used a custom-made questionnaire to evaluate the functional changes in daily activities after hardware removal as shown as follows. Patient's Evaluation after Hardware RemovalAnkle and Distal Tibia Fractures ORIFDate (year/month/day): ____/____/_____Patient's name: _______________________Registration number: _______________________Sex/Age: ______/________Mobile phone number: ___-___-__________Home phone number: ___-___-__________Occupation: _____________ Daily activity level Type of medical insurance: Name of diagnosis: ____________________ Ankle /Tibia /Calcaneus/Talus/LisfrancName of operation: ____________________ , broken hardware (Y/N)Date of operation (year/month/day): ___/____/________Date of Internal fixation implant removal (year/month/day): ____/____/_______ (Post-op:   months)Site of pain:Level of pain (VAS score) preop:  postop: none□0 low□1□2 mild□3□4 intermediate□5□6□7 severe□8□9 extremely severe□10Level of pain on a wet and gloomy weatherextremely painfulmore painfulno difference from other daysreducedvery reducedHow is your postoperative ankle joint movement?much more comfortablemore comfortableno changeuncomfortablemuch more uncomfortableWhat's your level of satisfaction about operation scar?very satisfiedsatisfiedfairunsatisfiedvery unsatisfied(6)How is swelling on operation lesion compared to pre-implant removal state?very reducedreducedno changeincreasedvery increased(7)How is skin sensation on operation lesion compared to pre-implant removal state?very sensitivesensitiveno changedullvery dull(8)Do you have any tingling sense on either operation lesion or other body parts after the implant removal? Please specify the body parts. ——(Yes/No) ——(Yes/No) ——(Yes/No)(9) Function evaluation(9.1) How was the “level of limping” accommodated after the surgery?(a)much improved(b)improved(c)no change(d)more limping after the surgery(e)much more limping after the surgery(9.2)How was the “level of discomfort when walking up the stair” accommodated after the surgery?(a)very much improved(b)improved(c)no change(d)more uncomfortable after the surgery(e)more uncomfortable after the surgery(9.3)How was the “level of discomfort when squatting” accommodated after the surgery?(a)very much improved(b)improved(c)no change(d)more uncomfortable after the surgery(e)much more uncomfortable after the surgery(9.4)How was the “level of discomfort at work” accommodated after the surgery?(a)very much improved(b)improved(c)no change(d)more uncomfortable after the surgery(e)much more uncomfortable after the surgery(9.5)How was the “level of discomfort during sports activities” accommodated after the surgery?(a)very much improved(b)improved(c)no change(d)more uncomfortable after the surgery(e)much more uncomfortable after the surgery(10)What is your general level of satisfaction about hardware removal surgery?very satisfiedsatisfiedfairunsatisfiedvery unsatisfied(11)If you were in the same situation, would you receive the same surgery again?Yes, I'd like to.No, I wouldn't.not determined.(12)Would you recommend the hardware removal surgery to others?Yes, I'd like to.No, I wouldn't.not determined.(13)Please specify your recommendation if you have.AOFAS score: Pre-hardware removal:Post-hardware removal: All interviews were performed by one of the authors (JIK). Pain was assessed on a 10 cm visual analog scale (VAS) anchored at one end by “no pain” and the other as “worst pain imaginable.” Other questions evaluated ankle stiffness and change in ankle discomfort while walking on an uneven surface, while walking upstairs, and while squatting. In addition, information was collected on patient satisfaction, intermittent swelling, and surgical scar formation.α = .05, β = .1) with use of Mann–Whitney test. Therefore, comparing two groups  met the statistical power requirements of this study. In comparing preoperative and postoperative pain, Wilcoxon signed ranks test was used. Fisher's exact test was used for comparing the frequency of complications. We used Spearman correlation test to analyze associations between patient's satisfaction and other independent factors: age, preoperative and postoperative pain scores, scar improvement, swelling improvement, and screw breakage.When comparing patients of tibia fracture with patients of ankle fracture, we used VAS pain score as the primary outcome indicator and determined effect size as 1 for retrospective power analysis. Thus a power analysis indicated that a sample size of 24 would provide 90% statistical power to detect an effect of this size between the two groups  separately. In the last 33 cases enrolled, before hardware removal we asked patients whether they would undergo hardware removal if clinician did not recommend surgery. Following that, responses were compared between patients who would and would not undergo hardware removal without a clinician's recommendation.Unless otherwise noted, the significance level for all statistical tests was set at 5% and all tests were two-tailed. Statistical analysis was performed using SPSS software  which was utilized throughout for this statistical analysis.We studied 80 fractures in 56 men and 22 women, all of whom had been followed up for more than 6 months after hardware removal . Mean age at hardware removal was 41.8  years. The 56 ankle fractures were classified using the Lauge-Hansen criteria: 39 (69.6%) of the 56 were supination-external rotation type, 3 (5.4%) were supination-adduction type, 13 (23.2%) were pronation-external rotation type, and 1 (1.8%) was pronation-abduction type. All 24 distal tibia fractures were classified as 43A according to the OA/Orthopaedic Trauma Association Classification [Radiographic bony union was confirmed for all 78 patients with 80 fractures, and all were followed up long enough after ORIF to have reached maximal recovery before scheduled hardware removal. When the achievement of bony union was uncertain on simple radiograph and physical examination, the confirmation of union was obtained by computerized tomography (CT). Consequently, the mean time from index fracture surgery to hardware removal was 23.6 (range 7 to 240) months.Mean pain scores were significantly lower after hardware removal overall and for ankle and tibial fractures, both after fixation with plates or screws, and among patients with preremoval pain scores of 3 or less .p < .001). Similarly, mean VAS score in the screw fixation group (14 fractures) significantly decreased from 3.2 (range 0 to 5) before to 1.1 (range 0 to 3) after hardware removal (p < .001). Again, no significant difference was found between these two groups (p = .868)  decreased significantly from 3.4 (range 0 to 6) to 1.3 (range 0 to 6) ( = .868) .About 72% of all patients reported subjective improvements in ankle stiffness, while about 89% of the patients improved walking on uneven ground, climbing stairs, and squatting . 63 80..p = .347). The degree and severity of intermittent ankle swelling decreased in 58 (72.5%) patients, while it increased in 4 (5%).Complications of screw breakage occurred in four patients, two of whom were with distal tibia fractures and the others with ankle fracture. None complained of symptoms because of remaining screw fragment. The frequency of that complication did not differ significantly between the two groups  significantly improved from the mean score of 2.21 to the mean of 0.77 . Of thisOf the last 33 patients enrolled, 24 (73%) underwent hardware removal on the clinician's recommendation rather than their own request, and 18 (75%) of the 24 patients reported satisfaction with hardware removal surgery. Another five patients all showed fair response although their pain was reduced. Only 1 (4.17%) of the 24 patients was dissatisfied with the surgery, the reason given being a hypertrophic scar and broken screw.ORIF of displaced ankle fractures is one of the most common surgeries in the orthopedic field and had showed better outcomes than closed reduction and cast immobilization , 10, 11.However, the indications and the clinical need for routine hardware removal after the treatment of distal tibia or ankle fractures by ORIF are disputed, especially when hardware-related pain is negligible . Thus, tPrevious outcome studies on hardware removal have been limited to hardware-related pain. Brown et al.  and KeatOur study has several limitations that warrant consideration. First, we did not use a control group. Determining the effect of routine implant removal by a randomized trial, such as sham procedure, is difficult for ethical or methodological reasons. For example, patients can easily know the existence of their implant because hardware around ankle joint is usually prominent onto skin, which prevents blinded study and placebo effect. Therefore, we recommended routinely removing hardware from all patients and separately analyzed subgroups that had mild symptom and therefore less motivation to have hardware removed. Second, standard functional evaluation score, such as American Orthopaedic Foot and Ankle Society ankle-hindfoot functional score, was not performed. But this was because the patients did not complain of significant pain or other discomfort expecting functional impairment. Findings of physical examination such as ankle movement also were not included in questionnaire of this study, which could have been less biased by the patients' expectations. Despite these limitations, we believe that this outcome of study could be used to develop prospective cohort or randomized controlled trials focusing on genuine effects of routine hardware removal.Our results of hardware removal after ORIF for an ankle or distal tibia fracture, even in mild symptoms, improve the functional daily activities in the patients' perspective and high patient satisfaction, supporting the recommendation to routinely remove hardware from these patients.