A maladaptive response to surgical stress might lead to postoperative complications. A multidisciplinary approach aimed at controlling the surgical stress response may reduce procedural complications and improve patients’ quality of life in the short and long term. Several studies suggest that psychological interventions may interact with the pathophysiology of surgical stress response, potentially influencing wound repair, innate and adaptive immunity, inflammation, perception of pain, and patients’ mood. The aim of this systematic review is to summarise the effects of perioperative psychological interventions on surgical pain and/or anxiety in adult patients scheduled for elective general abdominal and/or urologic surgery.We conducted a systematic review of controlled clinical trials and observational studies involving psychological interventions for adult patients scheduled for elective general abdominal and/or urologic surgery. Only studies reporting pain and/or anxiety among outcome measures were included in the systematic review. The following psychological interventions were considered: (1) relaxation techniques, (2) cognitive-behavioural therapies, (3) mindfulness, (4) narrative medicine, (5) hypnosis and (6) coping strategies.We examined 2174 papers. Among these, 9 studies were considered eligible for inclusion in this systematic review (1126 patients cumulatively): 8 are randomised controlled trials and 1 is an observational prospective pre/post study.Psychological characteristics widely influence the pathophysiological mechanisms underlying the neuroendocrine and inflammatory response to surgical stress, potentially interfering with surgical outcomes. Psychological interventions are technically feasible and realistically applicable perioperatively during abdominal and/or urologic surgery; they influence the pathophysiological mechanisms underlying maladaptive surgical stress response and might have positive effects on patients’ surgical outcomes, such as pain and anxiety. The optimisation of perioperative care may reduce postoperative complications and undesirable sequelae of surgery such as pain, fatigue, depression, and prolonged convalescence  performed the records screening (title and abstract) by independently cross-checking data from identified studies with inclusion/exclusion criteria. A third author (IL) resolved the conflicts. The following data were extracted from the selected papers using a uniform spreadsheet: study identifiers, methods, examined interventions, and surgical outcomes.A flow chart of the selection process used to identify eligible studies is shown in Fig. Information on psychological treatments and surgical outcomes in the selected studies is reported in Table In this systematic review, we summarise the effects of perioperative psychological interventions  on surgical pain and/or anxiety in adult patients scheduled for elective general abdominal and/or urologic surgery. Several studies suggest that psychologic/psychosocial, preoperative patient factors directly interact with the pathophysiological mechanisms involved in the surgical stress response . Interestingly, the authors observed that patients treated with perioperative relaxation therapies had higher hydroxyproline deposition in the wound (i.e. expression of tissue repair) than those in the control group .Psychologic/psychosocial patient factors have been demonstrated to interact with perioperative inflammation , and pre- and postoperative anxiety , while no significant effects were associated to postoperative analgesic use  or to conditions where anxiety and stress may affect patients outcomes (e.g. cardiac surgery). Moreover, differently from what was observed by Szeverenyi and colleagues, we observed a reduction in postoperative pain as well as a reduction in postoperative analgesic use in patients receiving psychological therapies.As far as we are aware, this is the first systematic review focusing on the effects of psychological treatments on surgical pain and anxiety in patients undergoing abdominal and/or urologic surgery. Previous systematic reviews and metanalyses aimed at assessing the effects of psychological interventions in the context of orthopaedic or cardiac surgery. Results from our review are generally consistent with those obtained from studies involving orthopaedic or cardiac surgery patients. In particular, in a systematic review of 62 relevant studies published from January 1980 to September 2016, Szeverenyi and colleagues found that psychosocial interventions significantly reduced postoperative pain . More objective indicators of intervention success  were used only in two of the identified studies.Finally, the treatments explored and the outcomes observed in this review are different among the selected studies. For these reasons, a synthesis of the evidence on effectiveness of psychological treatments in reducing perioperative anxiety and pain has not been provided. Nonetheless, results seem to suggest a positive effect on anxiety and pain, that certainly merits further investigation in the abdominal/urologic setting.In conclusion, a maladaptive response to surgical stress negatively influences perioperative outcomes. Psychological characteristics widely influence the pathophysiological mechanisms underlying the neuroendocrine and inflammatory response to surgical stress, potentially interfering with wound repair, innate and adaptive immunity, inflammation, perception of pain, and mood. Interestingly, perioperative psychological interventions  have proved effective on improving patients’ anxiety and pain, and have been shown to be technically feasible and realistically applicable perioperatively during abdominal and/or urologic surgery.


NLRP3-, MEFV- or TNFRSF1A gene. However, no systematical analysis of the clinical and psychological presentation of pain has been performed to date.Pain is the clinical hallmark of patients in patients with autoinflammatory diseases (AID) caused by variants of the NLRP3-, MEFV- and TNFRSF1A gene and clinical signs suggestive of an AID were retrospectively included in this monocentric cross-sectional case-series study. Patients were examined and interviewed using the German pain questionnaire. The hospital anxiety and depression scale (HADS) was applied to screen patients for anxiety and depression.Twenty-one symptomatic patients with variants in the n = 20; 95%). Pain symptoms were treated continuously with analgesic or co-analgesic drugs in 10 patients (48%). Five patients (24%) have been positively screened for concomitant depression or anxiety.Twenty out of 21 AID patients (95%) reported pain at the time of examination. Mean current pain intensity in all AID patients comprised 3.6 ± 1.3 and mean maximum pain intensity was 7.0 ± 1.6 on a 11-point numeric ranging scale (NRS). In 15 patients (71%), pain was present for more than 60 months. Ten patients (48%) experienced recurrent attacks with asymptomatic intervals and 7 patients (33%) suffered from constant pain, while 4 patients (19%) experienced both. Nociceptive pain including musculoskeletal and visceral affection was the most prominent type of pain (Early and prompt diagnosis is necessary to provide multimodal pain treatment and to avoid the development of chronic pain in patients with AID. Pain is one of the predominant characteristics in patients with autoinflammatory diseases (AID), including the cryopyrin-associated periodic syndrome (CAPS), familial Mediterranean fever (FMF) or tumor necrosis factor receptor associated periodic syndrome (TRAPS). It is also the experience of pain that significantly impacts patient’s daily life activities and drives patients with autoinflammatory syndromes to seek medical care and to use non-steroidal anti-inflammatory drugs . AlthougThe clinical picture of AID are commonly characterized by painful flares of systemic inflammation in joints, skin, muscles, eyes and serosal surfaces, accompanied by unexplained fever and elevated acute phase reactants . InvolveNLRP3 gene, FMF is caused by sequence variants in the MEFV locus encoding the inflammasome complex pyrin [TNFRSF1A gene, which encodes the TNF receptor TNFR1. These mutations have been associated with an accumulation of mutated TNF receptors in the endoplasmic reticulum due to inadequate shedding, thus triggering an inflammatory response [CAPS, FMF and TRAPS are all caused by a dysregulation of the innate immune system. While CAPS is mediated via gain-of-function mutations in the ex pyrin , 11. Dowex pyrin . In contresponse .NLRP3, MEFV or TNFRSF1A.Prompted by the leading symptom of severe whole body-pain in one patient carrying the NLRP3 Q703K (+/−) low penetrance variant (no. 9), we planned to investigate clinical and psychological characteristics of pain in a larger cohort of AID patients. Therefore, we have consecutively investigated 21 patients with 1) clinical symptoms compatible with either CAPS, FMF or TRAPS and 2) genetically proven low penetrance variants or pathogenic mutations in the respective genes, including NLRP3 (exons 4 and 6), MEFV  or TNFRSF1A . Detailed demographic data including sex, age, ethnicity, underlying mutation and age at disease onset were collected. Medical data collected and evaluated include clinical manifestations, disease course, elevation of inflammatory markers (including C-reactive protein (CRP) in mg/dl, serum amyloid-A (SAA) values in mg/dl), cerebrospinal fluid (CSF)  and magnetic resonance imaging (MRI) as well as AID-specific treatment. Written informed consent according to local ethics committee guidelines of the Ludwig-Maximilian University (project no: 600–15) and in accordance with the Declaration of Helsinki were obtained from each patient. A proportion of patients presented herein has been included in a previous clinical study [Between January 2016 and March 2018, a retrospective analysis of 21 patients with clinically and genetically determined AID was conducted at the Institute of Clinical Neuroimmunology in cooperation with the interdisciplinary Pain Centre, both located within the University Hospital Munich (LMU). All patients were referred to our outpatient clinic by medical specialists including rheumatologists and neurologists. Inclusion criteria were defined as a clinical presentation suggestive for AID and the detection of low penetrance or known pathogenic mutations in the P3 exons  and 6, Mwww.DGSS.org). Its modular approach to pain assessment consisted of demographic data, pain variables , sensory and affective qualities of pain , triggering and relieving factors as well as current pain treatment procedures. A numeric rating scale (NRS) scale ranging from 0 to 10  was used to assess patients’ subjective intensity of current, average and maximum pain intensity within the last 3 months. The affective pain quality summary score  was calculated by summing the responses of each item including miserable, terrible, horrible, awful. A cut-off value of ≥9 was regarded as increased affective pain experience. According to Korff [Patients were structurally interviewed for the presence, intensity, location and characteristics of pain using the German pain questionnaire  was used to screen AID patients for emotional distress including depressive and anxious episodes. Each item is scored on a response-scale with four alternatives ranging between 0 and 3. All responses are summed to obtain the two subscales of depression and anxiety. The most reliable cut-off values to screen successfully for mental disorders are as following: ≥ 10 on the HADS depression subscale, and ≥ 6 on the HADS anxiety subscale .r with Prism 6.01 software .Frequencies and percentages were used as descriptive statistics for categorical variables. To describe numerical variables, mean and standard deviation were used. Correlations are calculated using the Spearman’s rank correlation coefficient NLRP3 gene, while no other mutation was detected in NLRP3, MEFV or TNFRSF1A. Physical therapy, oral analgesics and psychotherapy partially improved her symptoms.In 2016, a 55-year-old former employee in the field of quality management was referred to our department from the psychiatry ward because of unspecific “total body pain”. She initially sought psychiatric treatment due to her schizoaffective disorder, which began after her father’s death in 2002. At the same time, she developed persistent pain in all joints with radiation into the entire musculature. Pain qualities were described as “dragging” and “stabbing”. She had seen numerous specialists, including orthopedic surgeons, neurologists, rheumatologists and pain specialists, without receiving a definitive diagnosis. On clinical examination, she exhibited an increased sensitivity to pain over the entire body and displayed a diffuse weakness in all limbs. Maximum pain intensity was 9.0 on a 11-point numeric ranging scale , while average pain intensity was 6.0 at the time of initial contact. A comprehensive differential diagnostic workup was undertaken. On brain MRI, multiple, supratentorial white matter lesions were present, which remained stable over time. MRI of the cervical spine showed no pathological findings. EMG and nerve conduction studies were normal. Audiometry detected a sensorineural hearing loss in the right ear, while ophthalmological examination showed a keratoconjunctivitis on both eyes. Laboratory testing repeatedly showed increased serum amyloid a (SAA) levels, but no evidence for an underlying rheumatological disease was found. Taken together, the clinical and paraclinical parameter pointed to a possible autoinflammatory condition. Genetic testing revealed a heterozygous Q703K substitution encoded by exon 3 of the n = 9). Aberrations in the MEFV gene included the pathogenic V726A (n = 2), M694V (n = 1), M680I (n = 1) mutations and the low penetrance substitution I591T (n = 2). In the TNFRSF1A gene, the low penetrance variant R92Q , 5 heterozygous) was exclusively found  were included in the study. All patients were Caucasian adults. The median age at study entry was 42 ± 12 years. The only NLRP3 variant found was the low penetrance substitution Q703K  showed a recurrent disease course with flares and no intermittent symptoms. Organ involvement included the musculoskeletal system , eyes , skin , gastrointestinal tract  and CNS . Of these CNS manifestations, two patients suffered from recurrent aseptic meningoencephalitis , and one from cerebral vasculitis with ischemic strokes (no. 1).The median age at symptom onset was 28 ± 4 years. Most patients , CRP  and leukocytosis . Lumbar puncture was performed in 13 patients. CSF abnormalities were found in 8 patients (36%). MRI was performed in 16 patients. Ten of these patients (63%) showed abnormalities (46%), including unspecific white matter lesions as the most common neuroradiological feature.Overall, 14 patients (64%) exhibited intermittently elevated levels of acute phase reactants including SAA (AID-specific therapies included colchicine in 4 patients (18%) and treatment with anti-IL-1 therapies in 10 patients (46%). All detailed clinical data are comprehensively summarized in Table Twenty out of 21 AID patients (95%) reported ongoing pain at the time of examination. Mean current pain intensity in all AID patients was 3.6 ± 1.3) on the 11-point numeric ranging scale (NRS) from 0 to 10. Mean maximum pain intensity was 7.0, ranging from 5.4 to 8.6 on NRS. Mean average pain intensity was 4.8 ± 1.2) at the time of examination. Average values for current, average and maximum pain intensity are shown in Fig. n = 13; 62%), arms , shoulders , hands  and head , while chest pain was only reported in 3 AID patients (14%). The vast majority of patients  reported pain in more than two body regions. Eighteen out of 21 total AID patients complained about ≥2 different pain qualities (86%). The most frequently reported pain qualities were “dragging” , “stabbing”  and “dull” . With the exception of patient no. 1, all patients displayed nociceptive pain including musculoskeletal and visceral pain affection. Only patient no. 1 showed an intermittent neuropathic pain episode with painful dysesthesias in the lower limbs due to a corresponding lesion in the thoracic spinal cord on level 12 five years earlier, which recovered completely during the following months. Detailed pain localizations and sensory qualities of each individual patient are presented in Table Pain was located most commonly in the legs n = 1; 62%, arn = 14; 67%), while the most commonly mentioned pain-relieving factor was physical exercise , while half of them were prescribed more than one analgesic substance. Eight patients received nonsteroidal anti-inflammatory drugs (NSAID). In two patients no. 3 and 20) steroids were administered, while in one patient (no. 21) a calcium channel blocker was administered to reduce pruritic pain  was found in 4 patients (19%). In the total patient cohort, the mean depression sub score (HADS-D) was 7.3 ± 1.1), while mean anxiety sub score (HADS-A) was 7.3 ± 0.9). Five patients (24%) scored ≥11 in the depression test scale  suggesting a possible depressive disorder, while also five patients (24%) had a score of ≥11 in the anxiety test scale  pointing to the potential cooccurrence of anxiety . Self-rer = 0.8207; p < 0.0001)     Fig. a, affectAutoinflammatory syndromes are rare, debilitating diseases and demand interdisciplinary treatment strategies due to multi-organ involvement. Although painful flares of skin, eyes, joints, muscles and CNS are part of the diagnostic criteria in AID , 18, 19,NLRP3, MEFV or TNFRSF1A. In our patient cohort, pain was present at a very high frequency, most commonly of nociceptive nature, following a chronic course and presenting as recurrent attacks and persisting pain alike. Clinical pain presentation was heterogenous and a distinct phenotype could not be attributed to a certain autoinflammatory syndrome. While other groups have found abdominal pain to be present in 95% of all FMF patients and have described an increased frequency of MEFV mutations in patients with epigastric pain syndrome [MEFV low penetrance variants. This finding may be partially explained by the low frequency of pathogenic mutation carriers in our study.Our index patient initially presented with “whole body pain”, which persisted and generalized to the point of causing significant disability for more than 10 years. Extensive evaluation by numerous specialists had been unrevealing. The diffuse nature of her pain together with psychiatric comorbidities aggravated finding the definitive diagnosis. Intrigued by this case, we subsequently set out to systemically review the pain patterns and the impact of psychological factors in patients with low penetrance variants in the syndrome –22, in oThe underlying mechanism for pain manifestation in AID patients is poorly understood. As almost all patients displayed nociceptive pain including musculoskeletal and visceral pain affection, an inflammatory nature of pain seems likely as patients with AID show a hyperinflammatory phenotype with increased levels of IL-1β, IL-6 and TNF-α following in vitro PBMC stimulation , 24. TheNotably, chronic pain is one of the critical factors for determining depression, and their coexistence tends to further aggravate and perpetuate the severity of both disorders. In our patient cohort, 24% of the study population were positively screened for depression and anxiety. Self-reported average working capacity and social life activities were significantly impaired due to pain manifestations. Here, the traditional explanatory causation model, whereby pain and disability induced by physical illness leads to mental health problems, becomes replaced by a more complex, integrated view on pathophysiology. In rheumatoid arthritis, for example, emerging data illustrate the negative effects of proinflammatory cytokines on monoaminergic neurotransmission, neurotrophic factors, and measures of synaptic plasticity. Accumulating evidence includes findings from clinical trials of immunomodulatory therapy, indicating that these interventions can provide benefits to mental health independent of improvements in physical disease scores .MEFV gene. Further and more sophisticated genetic investigations such as whole-exome sequencing and the exclusion of somatic mosaicism is desirable to detect yet unknown mutations. A further limitation is the relatively small sample size. Accordingly, a multi-centre study with larger number of patients is desirable to confirm our results.Patients with low penetrance variants have been reported to exhibit a milder phenotype, usually lacking both CNS symptoms and an up-regulation of the IL-1β axis –32. In cAs has been demonstrated by our index patient, it is common for rare AID patients to report unusual symptoms. As such, patients are frequently mislabelled as “hypochondriacs”, or as having a psychosomatic disorder. As a consequence, AID has to be considered in patients with heterogenous pain syndromes to effectively diagnose, treat and ultimately prevent patients from the development of chronic pain and the loss of functionality in their working and social life. Accordingly, we strongly recommend the routine use of supplementary questionnaires and patient-reported outcome measures amending the clinical status in a multidisciplinary setting .Taken together, our data highlight the complexity in assessment and management of pain and emphasizes the necessity of an integrated biopsychosocial view on AID as well as on other rheumatic diseases.Monogenetic autoinflammatory diseases (AID) are rare and debilitating diseases, caused by a dysregulation of the innate immune system. In patients with AID, pain occurs at a high frequency, regardless of the underlying genotype. Therefore, these patients will be encountered by pain specialists in clinical practice. Furthermore, pain in AID patients carrying low penetrance variants is of a nociceptive nature and often causes significant disability in social and working life. Contrary to widespread believe, affective components play an inferior role in pain perpetuation among these patients.


In an Expert Consensus guided by systematic review, the panel agreed that for open elective incisional hernia repair, sublay mesh location is preferred, but open intraperitoneal onlay mesh (IPOM) may be useful in certain settings. This analysis of data from the Herniamed Registry aimed to compare the outcomes of open IPOM and sublay technique.Propensity score matching of 9091 patients with elective incisional hernia repair and with defect width ≥ 4 cm was performed. The following matching variables were selected: age, gender, risk factors, ASA score, preoperative pain, defect size, and defect localization.n = 1938 (98%) pairs were formed. No differences were seen between the two groups with regard to the intraoperative, postoperative and general complications, complication-related reoperations and recurrences. But significant disadvantages were identified for the open IPOM repair in respect of pain on exertion , pain at rest  and chronic pain requiring treatment , in addition to rates of 3.8%, 1.1% and 1.1%, respectively, occurring in both matched patients. No relationship with tacker mesh fixation was identified. There are only very few reports in the literature with comparable findings.For the 1977 patients with open IPOM repair and 7114 patients with sublay repair, Compared with sublay repair, open IPOM repair appears to pose a higher risk of chronic pain. This finding concords with the Expert Consensus recommending that incisional hernia should preferably be repaired using the sublay technique. Two recently published systematic reviews and meta-analyses once again unequivocally demonstrated that the use of mesh procedures for repair of ventral and incisional hernias produces better results than suture techniques , 2. ThisThe following analysis of data from the Herniamed Registry now compares the perioperative and one-year follow-up outcome for open IPOM versus sublay technique for elective incisional hernia repair with a defect size of ≥ 4 cm. Propensity score matching was applied to obtain comparable patient collectives .As of February 1, 2019, 712 hospitals and surgeons in independent practice in Germany, Austria and Switzerland were taking part in the internet-based Herniamed Hernia Registry , 25. TheAs part of the information provided to patients regarding participation in the Herniamed Registry and signing the informed consent declaration, all patients were informed that the treating hospital or surgeon would like to be informed about any problem occurring after the operation and that the patient had the opportunity to attend for clinical examination , 26.All postoperative complications occurring within 30 days should be identified and documented. Therefore, the questionnaire sent to the general practitioner and patient at one-year follow-up once again enquires about any postoperative complications , 26. FurOne publication has provided impressive evidence of the role of patient-reported outcomes for both recurrence and chronic pain .The following analysis compares the prospective data of all patients with primary incisional hernia repair and a defect size of ≥ 4 cm   operated0 cm, III2), and risk factors like chronic obstructive pulmonary disease (COPD), diabetes mellitus, aortic aneurysms, corticoid medication, immunosuppression, coagulopathy, smoking, antiplatelet medication, anticoagulant therapy, and preoperative pain. Hernia-related variables influencing the outcome included the hernia defect size according to the European Hernia Society (EHS) classification  [The demographic and patient-related parameters include age (years), gender, American Society of Anesthesiologists (ASA) score I, II, III–IV, BMI (kg/m> 10 cm)  and hern> 10 cm) . Hernia > 10 cm) , 21, 26.> 10 cm) , 21, 26.p value ≤ 0.05 represents a significant result [All analyses were performed with the software SAS 9.4  and intentionally calculated to a full significance level of 5%, that is they were not corrected for multiple testing and each t result , 26. Thet result , 26.2), gender , risk factors (yes/no), ASA score , preoperative pain , defect size , drainage (yes/no), and EHS classification  [Propensity score matching is a suitable statistical method for formation of comparison groups from a very heterogeneous patient population. Persons with similar characteristics were assigned to the comparison groups and then compared with regard to the outcome variables. The propensity scores were calculated using a logistic regression model with selected matching variables. The following matching variables were selected: age in years, BMI (kg/mombined) , 21.The robust greedy algorithm was used for matching applying a caliper of 0.1 standard deviation , 21. UnaMcNemar’s test was performed to analyze the influence of the operation techniques on the outcome parameters  in the matched samples , 21.Furthermore, odds ratio estimates (adjusted for matched samples) and their corresponding 95% confidence intervals are given .p = 0.903) and body mass index (BMI) . For the categorical influence factors, significant differences were identified between these two surgical techniques with regard to the EHS width classification, EHS defect classification, drainage and preoperative pain  and lateral and combined defect localization than those operated on with open sublay technique. Patients with sublay repair already had preoperative pain more often. For the open sublay technique, drains were also used significantly more often.n = 1938 (98%) of patients  in addition to a rate of 3.8% pairs with pain occurring in both matched patients. Likewise, for pain at rest  and chronic pain requiring treatment , a difference was seen in favor of the open sublay technique. No systematic difference was found between the two surgical techniques for any of the other outcome variables.The standardized differences between the matching variables both before  and after matching (matched sample) are shown below Fig. . The difTo investigate the reasons for the significantly higher pain rates associated with open IPOM, the influence of using tackers for mesh fixation was analyzed additionally.For 760 of 1938 patients with open IPOM (39.2%) the mesh was fixed only with tackers or in combination with tackers. Compared with the patient group with no tacker mesh fixation, and only with suture fixation, no significant influence was identified on the pain rates at one-year follow-up ) and lateral and combined defects. Patients with open IPOM repair also reported preoperative pain less often than patients with sublay repair. Hence, propensity score matching revealed that the comparative patient collectives were characterized by a higher proportion of incisional hernias with EHS width classification III (> 10 cm) and lateral and combined localization as well as a smaller proportion of patients with preoperative pain.The use of tackers for mesh fixation in open IPOM was not found to significantly influence the chronic pain rates. Data of the possible influence of transfascial sutures on the chronic pain rates were not available.In systematic reviews and meta-analyses of open surgical techniques for incisional hernia repair, the only details reported on the outcome relate to the perioperative complications and recurrences –19.There are hardly any reports in the literature on chronic pain rates following incisional hernia repair. In a prospective study of 109 patients with elective incisional hernia repair with underlay composite mesh placement, chronic pain was defined as significant pain persisting after 3 months as assessed using a 10-point numeric scale  . After aIn a Cochrane review of open surgical procedures for incisional hernia repair, more postoperative pain was found in the intraperitoneal mesh group .Hence, it must be assumed that there are essentially no differences in the perioperative outcome and recurrence rate following incisional hernia repair in IPOM technique compared with sublay repair but that a higher rate of chronic pain must be expected. This appears to be independent of the tacker in comparison to suture mesh fixation technique. Therefore, the open IPOM technique should only be used when sublay repair is not possible. As such, the findings presented here concord with the recommendation of the Expert Consensus, indicating that for open elective incisional hernia repair, sublay mesh location is preferred, but open intraperitoneal onlay mesh may be useful in certain settings .Incorrect or missing data limit a registry , 26, 31.In summary, there is no systematic difference in the perioperative outcome or recurrence rate when comparing the open IPOM with the sublay technique for elective incisional hernia repair for large defects . However, significantly higher rates of pain on exertion, pain at rest and chronic pain requiring treatment to the disadvantage of open IPOM repair were identified. No relationship with tacker mesh fixation was identified. Hence, the open IPOM technique should only be used when sublay repair is not possible.


However, limited studies are available on the effect of topical curcumin. This study aimed to investigate the effect of curcumin ointment on knee pain in older adults with osteoarthritis.Some studies have shown the effect of oral administration of curcumin 5% ointment or Vaseline ointment twice daily for 6 weeks. Using a Visual Analog Scale, the severity of knee pain was measured at the beginning of the study, at the end of the fourth and sixth week. Data were analyzed using descriptive and inferential methods.This double-blind randomized placebo trial was conducted on 72 older adults with knee pain associated with osteoarthritis. The subjects were randomly assigned into an intervention and a placebo group to apply either P = 0.15). The mean pain intensity was significantly lower in the intervention group than in the placebo group at the third measurement (P = 0.02). The repeated-measures analysis showed that over time, the curcumin significantly decreased the mean pain intensity in the intervention group (P = 0.001). The mixed model showed an absolute difference of 1.133 (i.e. 11.33 mm) score which signifies a medium effect size and that the patient in the intervention group achieved the minimal clinically important difference.The mean baseline knee pain intensity was not significantly different between the two groups  ,  Knee pain is one of the most common health problems in older adults. Knee osteoarthritis is one of the most important causes of chronic knee pain in older adults . OsteoarIn Iranian people, the knee joint is more vulnerable and the prevalence of osteoarthritis and knee pain is higher due to various factors such as the inclination to sit on the ground, the form of the toilets, less participation in sports activities, standing cooking and housekeeping and other lifestyle-related factors . It is rA wide range of pharmacological, surgical and conservative mechanical treatments are being used in the treatment of osteoarthritis , then the degrees of freedom were corrected using the Greenhouse- Geisser test. The results showed that over time, the curcumin significantly decreased the mean pain intensity in the intervention group [F = 119.02, df = 1.329, and P = 0.001; Table P = 0.221). The value of between-group difference at T2 was 0.47 (i.e. 4.7 mm in the VAS) which signifies an effect size of 0.291. However, the mean pain intensity was significantly lower in the intervention group than in the placebo group at the end of the sixth week (T3) (P = 0.006). The value of between-group difference at this time was 1.14 (i.e. 11.4 mm in the VAS) which signifies an effect size of 0.664.As Table P = 0.71) but it did not significantly change afterward. However, in the intervention group, the amount of pain reduction between T1 and T2 was nearly threefold that of the placebo group (i.e. 1.64 score) (P = 0.001) and then continued to decrease at T3. Pairwise comparisons showed that all measurements in the intervention group were significantly different from each other (P = 0.001) and the pain intensity in this group had a significant decreasing trend during the study.Figure p <  0.05). Also, within-group changes were statistically significant in the intervention group.We calculated the changes in pain scores between T1 and T2 and also between T2 and T3. Table According to the linear mixed model effects, both the intervention and baseline pain had significant effects on post-intervention perceived pain Table . The mixcurcumin or Vaseline.During the study, none of the patients reported a local or systemic adverse event due to the use of curcumin ointment on the severity of knee pain in older adults with osteoarthritis was investigated. The outcome was assessed at the end of the fourth and sixth weeks. Although the results confirmed the progressive effect of curcumin ointment, however, the between-group difference was not statistically significant at the end of the fourth week. The value of the between-group difference was only 0.47 at this time. In other words, patients in the intervention group scored their pain only 0.47 (i.e. 4.7 mm) less than the placebo group which signified a small effect size at the end of the fourth week. Therefore, our first hypothesis cannot be accepted. However, the between-group difference was statistically significant at the end of the sixth week and the value of the between-group difference was 1.14 at this time. In other words, patients in the intervention group scored their knee pain 1.14 (i.e. 11.4 mm) less than the placebo group which signified a medium effect size at the end of the sixth week, and our second hypothesis was accepted. The mixed model also showed an absolute difference of 1.133 (i.e. 11.33 mm) which signifies a medium effect size. In addition to effect size, Polit and Beck (2017) also proposed the standard deviation as a criterion for operationalizing the minimum clinically important difference (MCID) in a clinical trial. This method interprets the results in the light of one-half standard deviation of baseline scores. Accordingly, a change equivalent to one half standard deviation of baseline scores of the comparison group is a good benchmark for interpreting that patients have achieved a minimal clinically important difference [In the present study, the effect of of fference . As the Although the placebo group experienced a slight but insignificant decrease in knee pain in the fourth week, this decrease did not continue in the third measurement.curcumin in older adults with osteoarthritis [curcumin is a very unstable compound and its oral administration provides poor bioavailability. This may have led to erroneous results in laboratory and clinical studies. Therefore, further studies are needed to evaluate the effectiveness of its oral extract on joint pain [curcumin, Gaffey et al. have also suggested further studies to address its effect on pain due to chronic osteoarthritis [Only a small study of topical application of an ointment containing turmeric and some other herbs in knee and hand arthritis pain is available in which 17 patients used the ointment for 42 days and found it beneficial in the improvement of joint pain and stiffness . A numberthritis , 28 and int pain . Referrirthritis .curcumin on alleviation of arthritis symptoms. They reported that only in half of the 8 articles reviewed did the clinical symptoms improved. In five studies no significant difference was found between the mean pain intensity in the groups used turmeric and those used commercially available pain drugs, and in these studies, only three studies used a proper method for randomization of the subjects [Daily et al. have also reviewed the clinical trials investigating the effect of turmeric extract and subjects .curcumin. Turmeric is one of the common herbs in traditional Iranian medicine. In Iranian traditional medicine, a mixture of curcumin and egg yolk has been used to reduce pain and accelerate the healing process of sprains, strains, and fractures [curcumin or diferuloylmethane and other volatiles that have antioxidant, antitoxic, anti-free radicals, and anti-inflammatory effects [curcumin had anti-inflammatory effects similar to hydrocortisone and phenylbutazone [curcumin showed a significant anti-inflammatory effect [curcumin in an animal model and reported that curcumin may have a central effect and exert its analgesic effect by affecting the opioid system. According to this report, curcumin exerts its analgesic effect by enhancing the release and effect of mediators such as dopamine, serotonin, and noradrenaline [Curcumin actually increases the number of presynaptic terminals associated with these neurotransmitters and increases their effectiveness by increasing the length of time they are open. Curcumin also increases the level of 5-hydroxytryptophan and increases the sensitivity of postsynaptic cells to this substance. It also inhibits monoamine neurotransmitter oxidase A, B enzymes, and increases the level of noradrenaline in the frontal lobe, all of which have analgesic effects [Curcumin has also been shown to inhibit inflammatory substances such as cyclooxygenase 2 [curcumin, when administered orally, has little absorption and bioavailability and is rapidly eliminated from the systemic blood flow [curcumin is greater than that of the gastrointestinal tract. A study also used a topical ointment containing turmeric to relieve osteoarthritis pain and reported this method as effective [curcumin on the reduction of knee pain associated osteoarthritis in older adults.The progressive reduction of knee pain in the intervention group of the present study can be attributed to the local effect of ractures –43 and tractures . Turmeri effects . Some stbutazone , 46. In y effect . Anotherrenaline . Curcumi effects . Curcumigenase 2 . It alsogenase 2 . Howeverood flow , 32, 44 ood flow .. Some rffective . Congruecurcumin.In the present study, while the knee pain reduction in the intervention group continued till the end of the study, the placebo group experienced only a slight reduction in pain at the second time, which did not continue thereafter. The slight reduction of knee pain in the placebo group at the second measurement might partly be attributed to the placebo effect. In other words, assuming that they are using a painkiller, made the patients in this group to express less pain in the second measurement. On the other hand, this group, like the intervention group, massaged the knee while using Vaseline and wrapped it with a cloth. This manner might also have contributed to the reduction of pain in the second measurement. However, because all of these factors were similar for the two groups throughout the study, the persistence of pain reduction in the intervention group can be attributed to the effect of topical application of curcumin use. It also makes the skin temporarily yellow. If this discoloration is not important to the patient, curcumin ointment can be used as a safe, relatively inexpensive, and effective way to relieve osteoarthritis joint pain.Generally, turmeric is a safe substance and has no reported side effects. Allergies to plants of the ginger family and jaundice are the only restrictions of curcumin ointment on joint pain, it is recommended to repeat the same study on larger samples as well as on other age groups with knee joint pain and also for pain relief in other joints. Also, the intervention in the present study continued for 6 weeks. Increasing the duration of treatment and follow-up can clarify whether the analgesic effect can be progressive. In this study, we used a VAS scale to measure knee pain. However, it is suggested that the WOMAC scale be used in future studies. In the present study, we also did not assess the effect of curcumin ointment on plasma inflammatory markers. However, it is suggested that some inflammatory markers be evaluated in future studies. Although we tried to keep the patients and the physician blind to the type of the prescribed ointment, however, due to the color of the curcumin ointment, the one who trained the patients and assessed the pain was not blind to the type of ointment, which may have affected the pain assessment. It is recommended that a third party assess the pain in future studies. Due to some errors in the values we initially used in the sample size calculation, we recalculated the sample size at the end of the study but the estimated sample size did not change.This study was conducted on a limited sample of elderly patients. Given the scarcity of studies on the effect of topical administration of curcumin ointment was effective in reducing knee pain in elderly patients with knee osteoarthritis. Therefore, it is recommended to use this ointment in the treatment of elderly patients with knee pain related to osteoarthritis.The present study showed that 6 weeks of topical administration of 5%


Fibromyalgia (FM) patients are likely to differ from healthy controls in muscle activity and in reactivity to experimental stress.We compared psychophysiological reactivity to cognitive stress between 51 female FM patients aged 18 to 65 years and 31 age- and sex-matched healthy controls. They underwent a 20-minute protocol consisting of three phases of relaxation and two phases of cognitive stress. We recorded surface electromyography normalized to maximum voluntary muscle contraction (%EMG), the percentage of time with no muscle activity (EMG rest time), and subjective pain and stress intensities. We compared group reactivity using linear modelling and adjusted for psychological and life-style factors.p < 0.001), pain intensity , and perceived stress  and lower mean EMG rest time . In the FM patients, compared with controls, the pain intensity increased more during the second stress phase , and the %EMG decreased more during the final relaxation phase . Within the FM patients, higher BMI predicted higher %EMG but lower stress. Leisure time physical activity predicted lower %EMG and stress and higher EMG rest time. Higher perceived stress predicted lower EMG rest time, and higher trait anxiety predicted higher pain and stress overall.The FM patients had a significantly higher mean %EMG .Retrospectively registered on ClinicalTrials.gov ( Fibromyalgia (FM) is currently considered to be a nociplastic pain condition, and several studies have reported plastic changes in the central nervous system (CNS) , 2. HoweThe CNS changes seen in functional magnetic resonance imaging (fMRI) in FM resemble those seen in other chronic pain conditions where peripheral nociplastic pain is evident, such as osteoarthritis (OA) and rheumatoid arthritis (RA). In OA and RA, the pain persists in some patients even after successful joint replacement in OA or normalization of inflammatory biomarkers in RA, indicating a nociplastic mechanism, similar to that in FM, initiated by peripheral pathology , 4.While no evident structural pathology has been found in the muscles of FM patients, the pain pattern of FM patients might be of muscular origin, as it resembles the pain pattern provoked by muscle trigger points in myofascial pain syndrome . The musFunctional changes in muscle activity can be studied using electromyography (EMG). Surface electromyography (sEMG) is a non-invasive and painless version of EMG, allowing undisturbed measurement during both relaxation and activity. It is unable to distinguish individual motor units but instead measures the sum of several muscle motor unit potentials .Electromyography (EMG) studies comparing FM patients and healthy controls have reported both decreased and increased muscle activity. Thieme et al. reported lower sEMG activity of the upper trapezius muscle at baseline and during alternating instructed relaxation and stress  when comparing 30 FM patients with 30 healthy controls . On the Pain-related reactions should not be studied without considering psychosocial factors. A body of evidence confirms the importance of negative  risk factors  and positive, protective, factors  for pain reactions. Negative factors are generally associated with increased pain and even with the development from acute to chronic pain, while positive, protective, factors associate with less pain .FM patients often report mental stress as one factor leading to worsening of their symptoms  and it hWe hypothesized that FM patients have higher resting muscle activity, and that experimental stress causes a greater increase in muscle activity and pain in FM patients than in healthy controls. We further hypothesized that these differences in reactivity between groups was associated with differences in prior stress levels, both state and trait anxiety, and with pain catastrophizing.We recruited 51 Finnish women with FM, aged 18 to 65 years, through the Helsinki University Hospital clinics, City of Vantaa health centre, and the private clinic of one of the authors (RM). Thirty-one healthy, female, age-matched controls were recruited from the staff of these health care units and from a local home economics organisation (Uudenmaan Martat ry). The controls were not required to be completely pain-free and were not excluded for minor, localized pain complaints such as mild hip or knee pain.Inclusion criteria for the FM patients were the American College of Rheumatology (ACR) classification criteria for FM from 1990 (ACR1990) .Both the patients and controls also participated in an oral glucose tolerance test and in bicycle ergometry, the results of which will be published later. These guided the selection of exclusion criteria, which were conditions likely to affect muscle function and metabolism measurements or to interfere with the ability to participate in the measurements: diabetes, heart disease, peripheral atherosclerotic disease, uncontrolled hypertension, neurological, neuromuscular or muscle disease, severe psychiatric disorders, continuous use of beta-blockers, beta-agonists or statins, any musculoskeletal condition that would prevent bicycle ergometry, and poor Finnish language skills that would affect the ability to answer the questionnaires.Consecutive patients meeting the ACR1990 criteria according to patient records were invited for a visit where the diagnosis of FM was confirmed by the research physician . Eighty-Thirty-two controls were originally recruited, but one was excluded because of a history of FM-like symptoms and the finding of 12/18 tender points in the physical examination, despite their reporting no current symptoms or spontaneous pain.We collected the data between November 2015 and June 2018.Subjects answered a questionnaire on medical history and provided details on height, weight, pain history, sleep problems, leisure time physical activity habits, working status, education, smoking, handedness, and any former participation in relaxation training Table .Table 1We calculated subjects’ body mass index (BMI) from their height and weight.“none”, “1–2 times per month”, “1–2 times per week”, or “more often.” Exercise intensity was rated on a four-point scale of “walking”, “intermittent walking and running”, “slow running or jogging”, or “fast running”. These we dichotomized into a single variable, with subjects classified as physically active if they reported both the highest physical activity frequency (which we took to represent frequent exercise) and physical activity intensity above the lowest level of “walking” . These cut-offs were further verified as producing the most closely balanced distributions in the FM patient and control groups.Leisure time physical activity frequency was rated on a four-point scale of We expected pre-existing stress, concurrent anxiety, and predisposition to anxiety to influence reactivity to experimentally induced stress and we therefore included the following validated questionnaires.“Never”) to 4 (“Very often”). For example, Item 6 asks “In the last month, how often have you found that you could not cope with all the things that you had to do?” [Perceived Stress Scale (PSS) measures prolonged subjective stress over the previous month: we used the revised 10-item version of this which yields scores from 0 to 40 (higher scores indicate more stress and less feeling of control). The individual items are rated on a five-point scale from 0  to 4 (“Very much so”).The State-Trait Anxiety Inventory (STAI)  consists“When you worked, how much did pain or other symptoms of fibromyalgia interfere with your ability to work, including housework?” Questions are answered on a visual analogue scale (VAS) from 0 (“No problem”) to 10 (“Great difficulty”).The Fibromyalgia Impact Questionnaire (FIQ) , 20 asse“Not at all” to “All the time”. For example, Item 3 states “The pain is terrible, and I think it is never going to get any better”. A sum score of 0 to 52 is calculated, with higher scores indicating a greater tendency to catastrophize when in pain.The Pain Catastrophizing Scale (PCS)  consistsThe research visit took place at the Helsinki University Hospital pain clinic. The subjects had been instructed to discontinue any beta-agonists, beta-blockers, or muscle relaxants normally used symptomatically before the visit. First, the subjects answered the validated questionnaires and other questionnaires to detail background information, medical history, and symptoms.The research physician then palpated the 18 tender points of the ACR1990 classification criteria.We completed a protocol of alternating phases of relaxation and induced cognitive stress. During this protocol, we recorded sEMG and heart rate, as well as self-reported pain intensity and stress. The results for heart rate measurements will be published separately. The measurement protocol is outlined in Fig. During the measurement, the subjects were instructed to remain still, seated in an armchair. The measurement consisted of five phases, alternating between relaxation and a mental arithmetic task to induce cognitive stress. Starting with relaxation, there were three relaxation and two stress phases, each lasting four minutes. At the start of the measurement, between each phase and at the end, the subjects were asked to verbally rate both their pain and stress on numerical rating scales (NRS) of 0 to 10 (0 meaning no pain or stress and 10 being the worst imaginable pain or stress).We used an sEMG monitor  with a sample rate of 1000 Hz to record sEMGs of left and right upper trapezius, biceps brachii, and erector spinae muscles. The sticky gel electrodes  for the sEMG measurement were attached as follows.For the upper part of the trapezius, the anode and cathode electrodes were placed 1 cm medially and laterally from the point in the middle on the line from the posterolateral edge of the acromion to the processus spinosus of the 7th cervical vertebra respectively. The grounding electrode was placed 2.5 cm caudally on the line orthogonal to the acromio-cervical line.For the erector spinae, the anode was placed 3 cm laterally from the processus spinosus of the 2nd lumbar vertebra and the cathode 2 cm caudally from the anode. The grounding electrode was placed 2 cm laterally from the midpoint of the line between the anode and the cathode.For the biceps brachii, the anode and cathode were placed 1 cm cranially and caudally from the point two thirds down on the line from the anterolateral edge of the acromion to the fossa cubitae, respectively. The grounding electrode was placed 2.5 cm laterally from the midpoint of the line between the anode and the cathode.For relaxation, subjects could choose between silence or calm classical music  No. 3 in D Major, BWV 1068: II. Air (“Air on a G String”), and the Goldberg variations).For the arithmetical task, subjects listened to a recording of 14 series of 10 random numbers from 0 to 9 with background white noise calibrated to 60 dB. The subjects were instructed to mentally sum the numbers and asked to give their answer at the end of each series. They were told whether their answers were correct or incorrect but for four of the series they were told they were wrong regardless of their answer. We modelled this protocol on work by Thieme et al. .At the end of the procedure, we measured the maximum voluntary contractions (MVCs) of the monitored muscles. For each pair of muscles, the trapezii, the bicipites, and the erectores spinae, subjects were instructed to produce maximum force in an isometric contraction for 10 seconds against resistance provided by the same research physician. The MVC was recorded twice for each pair of muscles at an interval of 1 minute.The subjectively rated pain levels and perceived stress during the protocol, together with the EMG recordings, formed the psychophysiological measures evaluating our main outcomes: pain and muscle activity.We used Matlab R2017b for signal processing. The raw sEMG was first detrended to a mean amplitude of zero. The signal’s power spectrum was then inspected visually to identify sharp peaks of alternating current (AC) noise caused by various electronic devices, most commonly at 50 Hz and multiples thereof. Noise peaks were removed using interpolation to flatten the power of the noisy frequency spectrum range of 1 Hz to the mean power of frequency range 0.5 Hz above and below the noisy range. Finally, a fifth-order Butterworth low-pass filter was applied to remove frequencies above 450 Hz not containing significant EMG activity.We chose %EMG and EMG rest time as the outcome measures of muscle activity. As these are calculated using the MVC, they would likely minimize individual differences in, for example, muscle mass and thickness of subcutaneous tissue, which might affect absolute sEMG values.We calculated the root mean square of EMG amplitude with a 100-ms non-overlapping window for the relaxation and mental arithmetic phases. For the MVC recording, a 1000-ms non-overlapping window was used for better reproducibility in obtaining MVC . We usedWe then calculated the normalized EMG in percentage (%EMG) by dividing the absolute EMG of each muscle by the muscle MVC. This allowed the use of mean %EMG of all recorded muscles to evaluate overall muscle tension.EMG rest time is the proportion of time the muscle is at rest with no significant muscle activity. We used the definition of sEMG less than 0.5 % of MVC and the 100-ms window described above to calculate this .For the baseline values of %EMG and EMG rest time, we used the mean over the first 30 seconds at the beginning of the recording.For statistical analyses, we used R version 3.5.3 . For general linear modelling, we used the lme4 package for R .A combination of visual inspection of histograms and the Shapiro-Wilk test determined that most demographic, psychological, and symptom scores were non-normally distributed, due to the low scores reported by the controls. Therefore, we compared FM patients and controls using the Mann-Whitney U test for continuous variables, and the chi-squared test for categorical variables.We calculated Pearson correlation coefficients to test for correlation between questionnaire data and %EMG, and pain and stress intensities during the measurement. We tested for correlations in the whole study population and within FM patient and control groups.Y ~ Group + Phase + Group:Phase. A second model was adjusted for BMI, smoking (smoker vs. non-smoker), leisure time physical activity (active vs. inactive), trait anxiety (STAI-B score), and preceding stress (PSS score).The main objective of our study was to determine whether FM patients and controls reacted differently to the repeated alternating relaxation and stress. We tested the change from baseline for %EMG, EMG rest time, pain, and stress during the different phases with general linear models. The base model tested the interaction between group and time for each outcome Y, written as We used trait anxiety instead of state anxiety, as the more stable characteristics of the subjects were of greater interest. In any case, the correlation between the sum scores of the two anxiety scales was very high.Secondarily, we evaluated the effect of lifestyle and psychological factors on stress reactivity within the FM patient subgroup. For this, we tested for interactions between time and the following possible predictors of the outcome measures: trait anxiety, preceding prolonged stress (PSS score), FM symptom severity (FIQ score), catastrophizing (PCS score), BMI, smoking, and leisure time physical activity.p > 0.05), the variable was removed as inconsequential to the model’s fit. If the models differed significantly (p < 0.05) and the fit of the reduced model was worse (Akaike information criterion increased), the variable was retained. After testing each variable individually, a level-one reduced model, which contained only the retained variables, was constructed.We constructed a reduced model which aimed to find the minimum number of variables which predicted the observed data well. The significance of these likely predictors and interaction terms was tested hierarchically. For each outcome variable, a full model containing all likely predictors was compared to a reduced model with one predictor variable removed. We used maximum likelihood (ML) analysis of variance (ANOVA) testing. If the model with a variable removed did not differ significantly from the full model  whether the reintroduction of any individually removed variable would significantly improve the model’s fit. The resulting level-two reduced model was then again tested with individual removal of the remaining variables and so on until the fit of the model no longer improved significantly: this was used as the final reduced model.Forty-seven of the 51 patients (92 %) fulfilled the ACR 2016 diagnostic criteria for FM in addition to the ACR 1990 criteria. Patients were often unable to report the exact duration of FM symptoms and provided only estimates such as “at least ten years”. The duration of FM was thus stratified into two classes, under 3 years or 3 years and over . Most paThe patients had higher BMIs and were more likely to smoke or have other chronic diseases than the healthy controls. FM patients also reported more problems with sleeping, lower leisure time physical activity, and greater pain intensity over the previous week than controls, and were more likely to use medication Table .n = the number of answered questions) [On the FIQ, 13 patients left at least one item blank. These missing data were imputed by multiplying the score by a factor of 10/n (where estions) .The FM patients perceived their overall stress level (PSS) as higher and had greater state and trait anxiety (STAI-A and STAI-B) than controls. The results, along with FIQ and PCS scores for the FM patients, are shown in Table The mean absolute sEMGs of the individual muscles of the FM patients was mostly similar to those of the controls. Patients had higher values at 0.05 significance level only in the left trapezius and the right biceps. The MVCs for the upper limbs, trapezii, and bicipites brachii bilaterally were significantly lower for the patients than for the controls, but the MVCs of the trunk (erectores spinae) were similar Table .Table 3The mean %EMG of all muscles was significantly higher in the FM patients than in controls Table . The EMGThe pain and perceived stress ratings reported by the subjects during the protocol were higher in the FM patients than the controls Table .Table 6We used general linear modelling to determine differences in responses to the measurement protocol and likely predictors of outcome measures.Baseline + Group × Time, significant group–phase interactions, indicating a difference in change from baseline, were found in the second stress phase (phase 4), where FM patients showed a greater pain intensity increase  0.04 to 1.38; p = 0.038), and in the final relaxation phase (phase 5), where the FM patients had a higher %EMG decrease . No group interaction was found for EMG rest time or stress.In the base model p = 0.028), and group (FM) – time  interaction for %EMG of -0.29   – time (stress phase 2) interaction for pain of 0.71 .The final models were:The only outcome measure with interactions was %EMG, where a higher baseline %EMG predicted a lower %EMG at each subsequent time point. Higher BMI predicted higher overall %EMG and lower overall stress whereas higher leisure time physical activity predicted lower %EMG and stress and longer EMG rest time overall. Higher PSS predicted shorter EMG rest time, higher FIQ predicted longer EMG rest time, and higher STAI-B predicted higher pain and stress overall. Smoking or PCS did not significantly affect the fit of the models Table .Table 7Table r = 0.45, p < 0.001), concurrent anxiety , and trait-anxiety , but in controls correlations were less (between 0.12 and 0.24). Similarly, stress during the procedure correlated in patients with perceived stress , concurrent anxiety , and trait anxiety , but, again, less in controls (-0.07 to 0.06),.In patients, pain correlated positively with perceived stress . Between resting EMG and psychological measures, there were small negative correlations .r = -0.33 in patients, r = 0.25 in controls), otherwise correlations between psychophysiological measures, pain, and stress were less (-0.09 to 0.19).There was a small negative correlation between resting EMG and stress during the procedure . Thus, our conflicting findings may be explained by the differences in the control groups, although these are not obvious: the control groups were both all-female and similar in age (mean age 46 vs. 48 years) with no obvious demographic difference [post-hoc testing, the patients with high FIQ scores and low leisure time physical activity tended to have shorter EMG rest times, while patients with high FIQ scores and who were also physically active tended to have EMG rest times similar to the patients with low FIQ scores, regardless of leisure time physical activity levels, though this was not statistically significant in the small subgroups.Within the FM patient subgroup, higher FIQ score predicted a longer EMG rest time. This was surprising, as we expected the patients with more symptoms to have a shorter EMG rest time. We speculate this is likely due to confounding factors. For example, in Both %EMG and EMG rest time were calculated in relation to MVC, which was lower in FM patients than in controls. This contributes to the patients having higher %EMGs and shorter EMG rest times. The absolute sEMG voltages were also significantly higher in the left trapezius and right biceps of the FM patients, with a tendency for higher values in the other muscles. Thus, our results support the theory of increased resting muscle tension in FM. As discussed above, this is in contrast to previous work by Thieme et al., reporting lower muscle activity, and Westgaard et al., reporting similar muscle activity in FM patients compared with healthy controls , 9.The MVCs of FM patients were lower than those of the controls in the upper extremities but comparable to controls in erector spinae muscles (in the trunk). This might indicate decreased neuromuscular control or upper body muscle mass of the patients. Westgaard et al. found the MVC of the FM patients for the trapezius, deltoid, and biceps brachii muscles to be 55 to 69 % of the MVC of the controls [Perceived stress during the stressful procedure seemed to be strongly linked to habitual experience of stress and anxiety in FM patients but not in healthy controls.As anxiety is known to be connected to the severity of chronic pain, we expected anxiety and pain to be correlated. Indeed, overall pain during the protocol correlated with anxiety in the FM patients in both the linear modelling and the correlation coefficients.However, neither %EMG nor EMG rest time correlate with any of the psychological measures in either subgroup. This suggests that short-term reactivity at least of muscle activity is not strongly linked to the psychological measures we used and may be mediated through other mechanisms.The FM patients showed an increase in pain during the second stress phase. Consistent with our findings, Crettaz et al. reported that stress lowers the pressure pain threshold of FM patients . SimilarFM patients often report an inability to relax. This phenomenon could be connected to the higher baseline values of sEMG and stress that we observed and is consistent with the observed reduced rest time. It is unclear to what degree lower physical activity is reflected in lowered MVC of the FM patients.2), and FIQ (44.5 vs. 49.8) [Our sample size did not allow for controlling all possible confounding factors, which limits the generalizability of the results. However, the patient group was representative of the population encountered in clinical settings, with many comorbidities and medications. As a measure of FM severity, the FIQ score can be used to estimate the similarity of our patient population to those in previous studies. For example, compared with the validation study of the Finnish-language FIQ by Gauffin et al., the FM patients had similar mean age (45.1 vs. 47 years), BMI (28.2 vs. 28.1 kg/ms. 49.8) .A single researcher conducted all measurements and clinical examinations, which minimized interobserver variation but did not allow for interrater reliability checks.The induction of stress in our study was successful, both groups reporting higher perceived stress during the phases of cognitive stress.Our study was not designed to measure dynamic muscle function. Accordingly, the conclusion of dynamic, rather than static, muscle function disturbance is not definitive. We strongly encourage further studies along this line of inquiry.Our study revealed that repeated cognitive stress increases pain intensity in FM patients. The increase in pain did not seem to be directly linked to an increase in muscle tension, as we did not observe that acute cognitive stress affected this. In accordance with earlier studies, we found lower maximum muscle function and increased resting muscle tension in FM patients compared with healthy controls. The role of muscle activity in flare-ups remains unclear, but stress and anxiety are implicated as promising targets in treatment of FM.


This cohort study assesses trends in the rates of initiation of pain medication among patients with newly diagnosed diabetic peripheral neuropathy and the types of pain medication prescribed from 2014 to 2018. We examined first-line analgesic medications prescribed to adults with a new diagnosis of DPN between January 1, 2014, and December 31, 2018. This study was approved by the Mayo Clinic institutional review board. Informed consent was waived owing to the use of preexisting population-level electronic health record data. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (4Included medications were prescribed during the first year after diagnosis and had not been prescribed in the preceding 12 months (nonopioids) or 3 months (opioids). Medications were regarded as concurrent if they were prescribed within 2 weeks of each other and were categorized as (1) guideline recommended ; (2) opioids, which are not recommended; and (3) acceptable   started a new pain medication after diagnosis . BetweenBetween 2014 and 2018, initiation of pain medication among patients with newly diagnosed DPN decreased by 35%. Overall, 43.8% patients initiating therapy were prescribed opioids compared with 42.9% who were prescribed guideline-recommended medications. Such high rates of opioid use by patients with DPN, a lifelong pain syndrome, are concerning because safer effective treatment options are available.5 likely because we did not exclude patients with preexisting pain or mood disorders, which are common in this population, making our study findings more generalizable. Our analyses are limited by the inability to examine the clinical context of pain management, including pain severity and other potential indications for opioid therapy, or contraindications to guideline-recommended treatments. Our sample size may be underpowered to ascertain factors associated with the choice of specific treatment regimens. Our data could not capture the duration of opioid therapy; thus, some prescriptions may have been for short-term rather than long-term use. In addition, the patients included in the study received care in 3 institutions and, as such, may not be representative of all patients with DPN. Further research is needed to examine DPN management trends nationally, identify factors associated with opioid use and barriers to evidence-based alternatives, and develop interventions to improve DPN management in clinical practice.Rates of opioid use exceeded those reported previously


Arthroscopic rotator cuff repair is a painful procedure, and treatment of emetic events associated with drugs used in the current multimodal pain management remains challenging. This study aimed to evaluate the effectiveness of ramosetron or ondansetron to relieve postoperative nausea and vomiting (PONV) and pain after arthroscopic rotator cuff repair.n = 39), ondansetron group (n = 43), and control group (n = 40). Then, 0.3 mg of ramosetron or 8 mg of ondansetron was administered intravenously at the end of surgery according to group. All patients received general anesthesia and multimodal pain management protocol including preemptive analgesic medication, fentanyl-based intravenous patient-controlled analgesia, and postoperative analgesic medication. Incidence of emetic events, rescue antiemetic requirements , complete response, pain level, and side effects were recorded in three periods: 0–6, 6–24, and 24–48 h postoperatively. The severity of nausea and pain was evaluated using a visual analog scale.In total, 122 consecutive patients undergoing arthroscopic rotator cuff repair were randomly allocated into three groups: ramosetron group (The ramosetron group tended to have a lower incidence and severity of nausea during the 6- to 24-h postoperative period and fewer rescue antiemetic drug requirements during the 0- to 48-h period than the control group, showing statistical significance. Additionally, the frequency of complete response of the ramosetron and ondansetron groups was significantly higher than that of the control group. No difference was found among the groups in the pain level except during the 0- to 6-h period. The two groups have a higher complete response during the 6- to 24-h period than the control group.Ramosetron use led to a lower incidence, mild severity of nausea, and reduced use of rescue antiemetic drug after arthroscopic rotator cuff repair during the 6- to 24-h postoperative period than the control.Level I, randomized controlled trials, treatment study Rotator cuff disease is one of the common causes of shoulder pain and is commonly treated by arthroscopic rotator cuff repair, in which patients tend to experience intense postoperative pain , 2. AdeqSeveral studies report variable responses to specific antiemetic drugs –14. AmonHowever, information on the effectiveness of ramosetron on PONV prevention in orthopedic patients is limited, and a few clinical studies have compared the prophylactic efficacies of ondansetron, ramosetron, and placebo after arthroscopic rotator cuff repair. Therefore, the aim of this prospective, randomized, double-blinded trial was to compare the antiemetic effectiveness of prophylactic administration of ondansetron, ramosetron, and placebo in high-risk patients with fentanyl-based PCA after arthroscopic rotator cuff repair. We hypothesized that  patientsThis article fits into the framework of translational orthopedic: how to evaluate the efficacy of ramosetron in surgery of arthroscopic rotator –25.This prospective randomized, double-blinded trial study was approved by the Hospital Institutional Review Board, and informed written consent was obtained from all reviewed subjects. However, in 2011, when we conducted the study, the Clinical Research Information Service (CRIS) was not implemented in our country. So, we enrolled in CRIS retrospectively for our experiments and then were issued the registration number (KCT0004460 on CRIS). The authors confirm that all ongoing and related trials for this drug/intervention are registered.n = 39), ondansetron (n = 43), or placebo (n = 40). So, we enrolled and followed up patients from September 1, 2011, to February 31, 2013.A total of 122 patients undergoing arthroscopic rotator cuff repair surgery between September 2011 and February 2013 were randomized to receive either ramosetron (The inclusion criterion was ambulatory patients undergoing arthroscopic rotator cuff repair surgery. The exclusion criteria were as follows: (a) previous surgery, (b) trauma history, (c) intolerance or allergy to any drugs used in the study, (d) severe bowel motility impairment, (e) administration of another antiemetic drug 24 h before surgery, (f) alcohol or opioid dependence, (g) history of cardiovascular or respiratory disease, and (h) renal or hepatic functional impairments.In addition, we excluded patients when general anesthesia was contraindicated. After assessing 147 patients for eligibility, we excluded 19 patients before enrollment for various reasons; subsequently, 128 patients were enrolled for randomization  for analysis.Initially, 42 patients were allocated to the ramosetron group and 43 to the ondansetron and control groups respectively. We excluded three patients in the ramosetron group and three in the control group according to the defined exclusion criteria, leaving 122 patients  were administered for preoperative preemptive analgesia on a call basis to all 122 patients before surgery. Anesthesia was induced with 1.5 to 2.5 mg/kg of propofol, 0.5 to 1.5 μg/kg of remifentanil, and 0.6 mg/kg of rocuronium and maintained with 1.5 to 2.5% of sevoflurane (50:50 mixture of oxygen and air) and 0.1 to 0.3 μg/kg/min of remifentanil. Then, 2 mL of medication containing either 0.3 mg of ramosetron  or 8.0 mg of ondansetron  or normal saline 2 mL was injected 10 min before the end of surgery. Then, IV-PCA opioid was introduced. The IV PCA regimen was comprised of a mixture of 2 mg of fentanyl and 120 mg of ketorolac and normal saline in a total volume of 100 mL. The IV PCA maintenance dose was allowed only at 1 mL/h, respectively. To avoid the bias of time-dependent different dose, bolus dose injection was not permitted.Patients were administered every 12 h for 3 days after surgery with the following medications: 200 mg of celecoxib, 75 mg of pregabalin, and 650 mg of acetaminophen. Rescue antiemetic  or analgesic  was administered according to the decision of blinded orthopedic physicians in charge of a patient in wards or upon patient’s request.Incidence of PONV and severities of nausea were recorded during three postoperative periods . Nausea was defined as a subjective unpleasant sensation associated with the awareness of urge to vomit and vomiting as the forceful expulsion of gastric contents from the mouth . The sevp value < 0.05 was considered statistically significant.We compared the ramosetron, ondansetron, and control groups with respect to outcomes. Sample size was calculated with reference to the results of a study comparing the effects of ramosetron and ondansetron on PONV associated with IV-PCA use in highly susceptible patients . We calcp = 0.007) (Table p = 0.003) during the 6- to 24-h period. However, it showed no statistical difference compared with the ondansetron group even though incidence and severity of nausea in ramosetron group is lower  than the ondansetron group (Tables p = 0.005) (Table p = 0.001), but no differences were also found among three groups during the other two periods (Table The preoperative characteristics and operative data were similar in the three groups Table . During 7) Table . ProphylThe most important finding of this study was that the incidence and severity of postoperative nausea were reduced effectively in the ramosetron group during the 6- to 24-h period compared with the control group after arthroscopic rotator cuff repair. The requirement for rescue antiemetics during 0- to 48-h period in the ramosetron group was significantly less than in the control group. Additionally, the frequency of complete response to administered rescue antiemetics in the ramosetron group and ondansetron group were significantly higher than that in the control group.Rotator cuff repair can potentially cause severe postoperative pain. Although arthroscopic rotator cuff repair is minimally invasive, severe pain during the first several days after surgery is common. Various methods, including injection or infusion of local analgesics, regional nerve block, and IV-PCA, have been proposed to effectively reduce postoperative pain.Current trends in the use of multimodal analgesia after surgery are increasingly popular to preventing postoperative pain. It involves administering a combination of opioid and nonopioid analgesics before, during, and after surgery that act at different sites within the central and peripheral nervous systems in an effort to improve pain control while eliminating opioid-related adverse effects. However, a combination of anesthetic and analgesic agents commonly provokes PONV , 29, 30,Ramosetron is a newly developed 5-HT3 antagonist with a higher affinity and longer duration of action than that of the previously developed 5-HT3 antagonist such as ondansetron and granisetron. Several previous studies have reported that ramosetron is superior to ondansetron in preventing vomiting and reducing severity of nausea after surgery , 31. RamPrevious investigations have shown that 0.3 mg of ramosetron was more effective than 4 mg of ondansetron in patients with spine surgery, total knee arthroplasty, and laparoscopic cholecystectomy , 22, 31 Notably, ramosetron was superior to ondansetron and placebo in preventing PONV and improving complete response in the 6- to 24-h period in the present study. PONV often occurs between 12 and 24 h after surgery due to several factors, including food intake after prolonged preoperative fasting, early ambulation, use of opiates for pain control, reduced effectiveness of intraoperatively administered antiemetics, or residual anesthetics . After 25-HT3 antagonists (ramosetron and ondansetron) are reported to have side effects including headache, dizziness, and drowsiness . In our Although ramosetron and ondansetron can reduce nausea within 24 h, there was no significant difference in vomiting. This may mean that ramosetron cannot control other factors involved in vomiting. The effect of other factors such as histamine, muscarinic, and dopamine receptors on vomiting is greater than that of serotonin receptors. Further discussion on this issue will be needed in the future.This study had several limitations. First, our study population consisted of patients with different severities of rotator cuff tear. Second, our data cannot explain why the ability to control pain management is superior in the ondansetron group. Because a good therapeutic effect of PONV can lead to increase amount of opioid use, this may reduce pain level. However, there were no differences in opioid consumption, and pain management was slightly better in the ondansetron group. The control of PONV does not influence pain level in our data. In addition, this study included a small number of cases. Further, pain was simply measured in accordance with each postoperative period without distinguishing non-resting pain and resting pain. Since the degree of pain may differ according to the activity of the individual, it should be taken into account when assessing the severity of pain.Ramosetron use led to a lower incidence, mild severity of nausea, and reduced use of rescue antiemetic drug after arthroscopic rotator cuff repair during the 6- to 24-h postoperative period than the control.


There is a literature gap concerning the management of undesirable effects of analgesics prescribed to pediatric inpatients and a need to improve education provided about pain management. The use of analgesics for the treatment of post-operative pain is common, however, such medications are known to have potential side effects. These undesirable secondary effects can have an important impact on patients and impede their recovery.A review of the literature was conducted in order to gain a better understanding of the challenges confronted by pediatric patients in the acute post-operative period in terms of the side effects of analgesics.An online search of keywords  using PubMed, Medline and Scopus databases, and using the snowballing method of reference tracking was conducted.A total of 10 studies  published between 1990 and 2019 were reviewed. Common side effects experienced by patients were nausea, vomiting, and pruritus. Patients' parents reported having many concerns about analgesic use and reported a lack of knowledge on pain medications and side-effect management.Areas of improvement in clinical practice include providing the patient and their parents with more information about the post-operative period, analgesic use, and side effects as well as prescribing appropriate treatments to alleviate side effects. This review reveals a lack of qualitative data on pain management and related undesired side effects in pediatric patients having undergone inpatient surgery in addition to the consequences on patients' daily living and on the self-care strategies they engage in to attenuate such effects. However, even if the best pain management is provided and pain is well controlled, recovery may be prolonged due to the side effects of pain medication.13 The use of analgesics such as opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs for the treatment of postoperative pain is common in both adult29 and pediatric patients.2 However, such medications are known in both populations for common potential side effects such as sedation, nausea, vomiting, constipation, itching, dizziness, headache, respiratory depression, and digestive organ irritability.29 A better understanding of the challenges confronted by pediatric patients in the acute postoperative period in terms of analgesic-caused side effects may present valuable details to improve care provided.Postoperative pain in pediatric patients has been associated with limitations in daily living such as reduced school attendance, extracurricular activities, social activities, household tasks, and sleep quality.A review of the scientific literature on the postoperative challenges confronted by pediatric inpatients was completed to identify the needs of patients and their parents after surgery and after hospital discharge. This brief report aims to answer specific questions relevant to 4 distinct themes: (1) Analgesic use and side effects: What are the common side effects of postoperative analgesics reported by patients? How do these side effects disrupt patients' quality of life? (2) Self-management strategies: What are the common self-care strategies that patients use to attenuate side effects of analgesics? (3) Education provided by healthcare providers: What education is provided by healthcare providers on analgesics and their side effects? What is the perception of patients and/or their parents on the education provided on analgesics and their side effects? (4) Patients' and parents' concerns: What are the concerns of patients and/or their parents in terms of medication use?20A literature search was conducted using the online databases of PubMed, Medline, and Scopus as well as using the snowballing method of reference tracking using combinations of the following terms: pediatric, analgesic, pain medication, side effects, adverse effects, nausea and vomiting, postoperative, postdischarge, self-care, self-management, management, self-care strategies, patient expectations, patient concerns, and education. Articles published between 1990 and 2019 were searched for. The year 1990 was chosen because this is when opioids were increasingly used and studied, and became the first line of treatment for pain.Studies included had to relate to postoperative analgesic use by pediatric patients. The literature search included peer-reviewed articles published in English and studies using pediatric patients or their parents as participants. The term parent refers to any adult responsible for the child's care and supervision. The search was also limited to studies investigating patients scheduled to undergo or who have undergone a surgery that required incision, anesthesia, and a postoperative hospital stay. Only studies investigating common medications used in North America were included. Articles that were excluded were those that investigated the postoperative period after 6 months, patients undergoing outpatient surgery, adult patients (mean age >18 years), and patients with cancer. These exclusions had the purpose of homogenizing the populations and narrowing the research being discussed.Articles were screened and excluded based on the relevance of their abstracts and on whether they fulfilled the criteria by 2 independent reviewers. The full texts of the remaining articles were selected, read, and summarized by one reviewer.Ten studies met the criteria. A summary of the characteristics and results of the studies included are presented in Table 27 morphine,24 codeine,25 meperidine,25 hydromorphone,25 hydrocodone,25 oxycodone,5 tramadol,17 aspirin,25 diclofenac,11 ibuprofen,11 and ketoprofen.17 Tesler et al.25 found that the patients in their sample were prescribed 3.1 analgesics in the 5 days after surgery. Side effects reported by patients were respiratory depression,17 sedation,9 nausea,17 vomiting,17 pruritus,11 dizziness,5 constipation,5 and urinary retention.17 No literature was found on how these side effects may affect patients' quality of life.The time window observed in the included studies ranged from the day after surgery to a few days after discharge. Analgesics that were administered or prescribed to patients after surgery were acetaminophen,Patients may engage in self-care activities to attenuate the severity and frequency of their side effects. However, no studies were found in which this was investigated in pediatric patients.18 Simons and Roberson18 found that, in the days after surgery, about half of the parents they interviewed reported the need for more information on pain management. Many parents reported feeling overwhelmed with the amount of information they had to take in about pain management and felt hesitant to approach busy nurses for more support.18 Parents identified the need for more involvement in the patient's recovery and the need for more support and education from nurses concerning analgesic use and side effects.18It was common for parents of patients to feel as though they are not adequately knowledgeable about pain management and potential side effects.27 Parents have expressed worries about the efficacy of analgesics, the change in medication intake schedule after transitioning from hospital to home, the overconsumption of medication, and the side effects of postoperative analgesics.27Parents also have concerns about their child's analgesic use.28 Although discussing pain management and side effects one-on-one with a healthcare provider is important, written information should be provided in addition to this.10 This combination would allow the patient and parents to not only discuss concerns with a healthcare provider but also look back at written information if forgotten. A mobile application containing information about the postoperative period may be useful for patients and allow for access at any time.19 The implementation of knowledge translation intervention programs such as Evidence-based Practice for Improving Quality, in which contextual program tailoring, leadership support, staff engagement, and time and resource allocation are important factors,22 has also been shown to improve patient pain outcomes in a hospital setting.22The results found made it difficult to address the specific queries of this review due to limited published research in the field. A major issue that came out of the review is that parents commonly report lacking knowledge about analgesic use and side effects. Pain management education should aim to provide parents and patients with adequate and consistent age-specific information about the possible side effects of postoperative drugs and their duration, and advise them on how to manage them.27 Patients and parents should be knowledgeable about analgesic use and the risk for side effects in the weeks before surgery and their concerns should continuously be addressed thereafter by the same team to avoid them forgetting information and to ensure correct and consistent education.26 Prescribing antiemetics based on the reason for symptoms and administering prophylactic treatment to patients is frequent.28 However, parents and patients may not be comfortable with the consumption of additional medications; therefore, clinicians should also educate patients on nonpharmacological strategies for pain management and side effects.This review highlighted that parents have many concerns about their child's medication use and side effects such as the efficacy of analgesics, the change in medication use after transitioning from hospital to home, the overconsumption of medication, and the side effects of analgesics.25 Additional studies using qualitative methods can allow us to gain a deeper understanding of the patients' perspective on which side effects they find most disruptive and how they manage them. Moreover, how daily living is affected and which self-care strategies are used are important to study because they may have a significant impact on recovery. Knowing which self-care activities patients engage in and whether they are effective is important so that they can potentially be recommended as alternative side effect management strategies.Furthermore, the fact that information given to patients and parents is being perceived as being inadequate may be due to a lack of research conducted on pediatric inpatients' perspectives on the challenges they experience postoperatively. Most studies investigating this topic have used pediatric patients who have undergone day-surgery. Although outpatients may be more at risk of feeling unknowledgeable after discharge, the invasiveness of inpatient surgery usually requires the consumption of more analgesics; therefore, they may differ in terms of postoperative experience. A systematic review including both populations should be conducted. Also, only 4 of the 10 studies reviewed used a qualitative approach for data collection.The authors have no conflicts of interest to declare.