Supplemental Digital Content is Available in the Text.The reliability and validity of International Pain Outcome questionnaire Spanish adaptation is confirmed in a large heterogeneous sample. Factor scores can be used as a global outcome analysis tool. Choosing perioperative suitable treatments requires reliable and valid outcome measurements. The International Pain Outcome (IPO) questionnaire has been widely used for quality improvement and research purposes within the PAIN-OUT network that has collected more than 550,000 data sets of postoperative patients in 200 hospitals worldwide. Our aim is to confirm psychometric properties of the Spanish version of the IPO questionnaire and its invariance by pain predictors.would have liked more pain treatment and opioid requirement was also estimated with logistic binary regression.Sample included 4014 participants within a large age range, who underwent different surgical procedures. Confirmatory factor analysis (CFA) assessed internal structure, considering invariance by sex, age, procedure, smoking, obesity, affective disorder, and chronic pain. Incremental predictive validity of factor scores on question would have liked more pain treatment was achieved.Confirmatory factor analysis verified original structure in 3 factors measuring pain intensity and interference (F1), adverse effects (F2), and perceptions of care (F3), with good internal consistency. Multigroup CFA analysis confirmed invariance by assessed pain predictors. Good incremental predictive capacity to identify Our study confirms the factor structure, supports reliability, and adds some evidence of convergent validity of the Spanish adaptation of the IPO questionnaire. The sum of scores in its main factors serves a global outcome analysis tool. Low scores in F1 and F2 with high scores in F3 would indicate optimal quality of care. After phase 1 analysis, they shortened the questionnaire to adapt it to the European population. From the Revised American Pain Society Patient Outcome Questionnaire, falls and sleep were combined. They eliminated the items how helpful the information was as well as the frightened and depressed items because they have a high correlation with anxious. They included the following 3 additional questions: interference with breathing, would have liked more pain treatment, and presence of previous chronic pain. Using principal component analysis, a 3-model factor structure was identified, explaining 53.8% of the total variance: pain intensity and interference, adverse effects, and perception of care.22As an outcome measurement tool, the International Pain Outcome (IPO) questionnaire22 ; (2) to test invariance and differential item functioning of the 3-factor structure by the patients' sex, chronological age, surgery type, current smoking, obesity, affective disorder, and presence of chronic previous pain27; and (3) to estimate the incremental predictive validity of the IPO factor scores on would have liked more pain treatment and total morphine consumption (defined as criteria of poor pain control).The general objective of this study was to evaluate the psychometric properties of the Spanish adaptation of the IPO questionnaire in a large clinical sample including patients who underwent different types of surgery. The specific objectives were as follows: (1) to obtain empirical evidence confirming the 3-factor structure for the IPO questionnaire found by Rothaug et al.29 The Spanish subsample of the European PAIN-OUT study was analyzed, which included n = 4650 patients recruited from 13 hospitals from 7 different regions of Spain. All centers were university hospitals (300–1000 beds) with an acute pain care unit. As the number of participants in the sample used for previous factorial validation studies was very low (less than 10% of the sample), we decided to maintain them in the current study to increase external validity and generalization capacity. Data were collected between February 2010 and December 2013 by trained research assistants, who followed a standard operating procedure provided by the PAIN-OUT project.20 Patients who accepted to participate completed the IPO questionnaire. The registered data were entered in a secured multi-institutional web-based database using a random identifier. As an inclusion criterion, it was required that patients were in their first postoperative day and in the ward for at least 6 hours. Exclusion criteria included being asleep, sedated, not in the ward at the time of data collection, and not able to communicate, including any language barrier, not able to read and understand questionnaires, and cognitive impairment .The IPO questionnaire developed by Rothaug et al.The study involving human subjects and the use of patient data for research purposes was approved by the Committee on Research Ethics of every participating center, and the research was conducted in accordance with the Declaration of the World Medical Association , and signed informed consent was obtained from all participants.The measures analyzed in the study correspond to self-report measures answered by the patients in the first day after surgery at the arrival to the surgery ward. Research assistants encouraged the patients to complete the questionnaires and could read the unanswered questions to patient once, intending that the items were all answered and that no problems had occurred because of a lack of understanding.22 Maximum likelihood (ML) estimator with missing values was used, and the overall goodness of fit was evaluated through the standard statistical measures3: the root mean square error of approximation (RMSEA), Bentler's comparative fit index (CFI), and the Tucker-Lewis index (TLI). Adequate model fit was considered for RMSEA <0.10, TLI >0.9, and CFI >0.9. The χ2 test was not considered as a fitting measure because of the strong dependence of this test with sample sizes . The internal consistency between items within each defined factor was estimated by omega coefficient  . A corrected item-scale correlation was calculated for each item. Because of the strong association between statistical significance for the coefficients and sample size, a corrected item-scale correlation was considered low to poor |R| >0.10, moderate to medium for |R| >0.24, and large to high for |R| >0.37 .21Statistical analysis was performed with Stata16 for Windows. Confirmatory factor analysis (CFA) was performed considering that the new adapted IPO questionnaire was developed after a theoretical rationale procedure based on the following steps: (1) adapting a new instrument for covering 3 specific domains (constructs/areas) related to the pain measure ; 2) reviewing all the items initially assigned to each domain to ensure that the contents were appropriate for the target population(s); and (3) providing a meaningful distribution and order to the new version of the questionnaire. Therefore, CFA in our study was performed assuming the existence of 3 latent theoretical factors from items measures on a 0 to 10 scale: factor 1 defined by 9 items measuring pain intensity and interference(s); F2 defined by 4 items measuring pain treatment-related adverse effects; and F3 defined by 3 items assessing the patients' perception of care: allowed to participate in pain treatment decision, pain relief, and satisfaction with pain treatment, with higher scores meaning better perception of care  analysis met the following criteria6: (1) the model specifying the items measuring each latent variable fits the data well; (2) all factor loadings are substantial  and statistically significant; and (3) no large modification indices exist that point to model misspecifications.Because of a steady association of the pain construct with variables such as sex, age (2 groups were defined based on the median in the own sample), surgery type, current smoking, obesity defined as body mass index greater or equal to 30 kg/md| >0.20, mild to moderate for |d| >0.50, and high to large for |d| >0.8016).Comparison for the raw factor scores between participants' sex, groups of age, surgery type, current smoking, obesity, affective disorder, and presence of previous pain was based on analysis of variance. Effect size for the mean comparison was based on Cohen's d coefficients  were part of the anesthetic protocol and not used to provide postoperative analgesia, so they were excluded. The value 30 mg per 24 hours was chosen to dichotomize the variable morphine equivalent consumption to high opioid consumption, based on previous literature.20As there are no gold standard measures of postoperative pain outcomes, the questions on the survey would have liked more pain treatment and high opioid consumption was estimated with logistic binary regression in 2 steps or blocks: (1) the first step or block entered and fixed the patients' sex, age, surgery type, current smoking, obesity, affective disorder, and presence of previous chronic pain; and (2) the second block added the 3 raw scores in the IPO questionnaire. Goodness of fit was valued with the Hosmer–Lemeshow test (adequate fitting was considered for P > 0.05), whereas the incremental predictive validity of the IPO scores was estimated with the change or increase in the Nagelkerke pseudo-R2 (∆R2) comparing first and second steps or blocks of the regression and the incremental discriminant validity with the increase in the area under the ROC curve (∆AUC2).The incremental predictive or discriminant validity of the factor scores measured through the IPO questionnaire on the question Of 4650 patients recruited, 636 did not participate in the study because of being asleep, sedated, not in the ward at the time of data collection (at least 6 hours in their first postoperative day in the ward), or not able to communicate (patient is deaf or is not able to communicate in any of the IPO available languages). Therefore, 4014 patients were analyzed. Figure pain intensity and interference (ω = 0.82), moderate for factor F2 adverse effects (ω = 0.61), and good for F3 perceptions of care (ω = 0.72). These results confirm the structure in three first-order factors for the IPO questionnaire in the whole sample .Figure http://links.lww.com/PR9/A96) contains the results to move from the single-group CFA obtained in the whole sample to the MGCFA to cross-validate the 3-factor structure across the groups defined by the participants' sex, age, surgery type, current smoking, obesity, affective disorder, and the presence of previous chronic pain. Good fitting indexes were obtained in the MGCFA models defined for assessing no differences in the structure for the IPO based on sex, age, current smoking, affective disorder, obesity, and presence of previous pain, whereas fitting was only moderate for the model measuring invariance by the surgery type. Nonsignificant results were found in the tests assessing invariance by sex , indicating a equally statistical structure for men and women. However, invariance reported significant results in the joint test for the rest of the groups tested in the MGCFA. Examining separately the standardized coefficients in each group, significant high scores (above 0.30) were achieved for all the items .Table S2  and adverse effects (P < 0.001). These 2 factors also registered higher mean scores as lower the patients' age, whereas the factor perception of care registered lower mean for older patients compared with other 2 groups of age (P < 0.001). Differences for type of surgery only reported differences for the factor measuring adverse effects; orthopedic surgery reported lower mean compared with both general (P = 0.007) and other (P = 0.004) surgeries. Current smoking reported less adverse events (P = 0.01).Table would have liked more pain treatment and for high opioid consumption, goodness of fit was achieved for the final model for the second step or block . Increase in the pseudo-R2 after including and fixing the variables defined into the first step or block indicated that the specific incremental predictive capacity of IPO factor scores was around 23%  and the specific incremental discriminative capacity was also around 23%  in would have liked more pain treatment. The predictive capacity of the variables included in the model for high opioid consumption was low (R2 = 0.057 and AUC = 0.626) and did not increase noticeably with the inclusion of factor scores (∆R2 = 0.027 and ∆AUC = 0.031). Significant OR coefficients were achieved for the factors measuring pain intensity and interference  and perception of care  in would have liked more pain treatment, whereas in high opioid consumption, significant OR coefficients were achieved for pain intensity and interference  and adverse effects , indicating that the probability of liking for more treatment was higher for patients who perceived higher pain intensity and interference and lower perception of care, while the probability of high opioid consumption was higher for patients who perceived higher intensity and interference and higher adverse effects.Table 20 The main results of this study provide evidence about (1) the structure of the IPO questionnaire in 3-factors ; (2) the invariance of the structure by sex, age, surgery type, current smoking, history of affective disorder, obesity, and presence of previous pain; and (3) the capability of the factor scores to predict would have liked more pain treatment.This study aims to test the psychometric validity of the IPO questionnaire in a large clinical Spanish sample with patients who underwent a broad range of surgical procedures and perioperative management.22 our CFA shows that interference with breathing and coughing was the item with the lowest factor loading (0.33) on F1 (pain intensity and interference). This could be related to the heterogeneity of the procedures included in the sample, considering that factor loading on this item increases in general compared with orthopedics procedures because limb procedures usually do not affect the respiratory system.20 The moderate adjustment of invariance by type of procedure could also be influenced by this item. For F2 (adverse effects), itch (0.32) is the factor with the lowest standardized coefficient, which may be due to the low frequency of occurrence and low intensity compared with other adverse effects.20 Itching was introduced in the IPO as one of the main adverse effects of intrathecal and epidural opioid treatments, but the frequency of occurrence in large sample studies has been around 6% to 18%,11 and although it is bothersome, its relevance in the functional status and morbidity of postoperative patients is arguable. Regarding perception of care (F3), the satisfaction item explains almost all the variability in that factor, in contrast to the original exploratory factor analysis by Rothaug,22 where the items loads were more balanced. Also, for F3, our study shows moderate internal consistency suggesting that pain relief, satisfaction, and participation in pain treatment decisions measure different aspects of postoperative experience in Spanish patients and should be treated separately. High participation and information about pain therapy, perceived by the patients, has been shown to be a predictor of less pain intensity, restriction with movement, and dissatisfaction in the German population.18 Unlike other countries, such as the United States, where both participation and satisfaction with treatment are high,28 Spanish patients, on average, perceive that they participate less in pain treatment, but despite this, satisfaction is comparable to other countries.20 This may be due to sociocultural differences, the fact that health care is public in Spain, and the degree of involvement that Spanish patients want to have in treatment decisions may differ from other countries.Similar to the initial IPO exploratory validation study,12 Raw scores show differences by sex in intensity and interference and adverse effects, but not in perception of care. The higher sensitivity to pain in women compared with men seems to occur after puberty,4 and it is believed to be related to increased occurrence of pain due to the menstrual cycle, that generates a larger painful memory network and higher pain sensitivity,5 a fact that could explain the increase in pain interference scores. Higher frequency of adverse effects could be associated to pharmacokinetic differences in the metabolism of analgesic medication, as shown by the fact that plasma morphine concentrations with the same dose are higher in women and exposes them to higher frequency of adverse effects.10 Interestingly, although men had lower scores in intensity of pain (F1) than women, in the logistic regression analysis, being a man is a predictor of would have liked more pain treatment.The analysis presented here suggests invariance of the factor structure for sex, age, previous chronic pain, current smoking, obesity, history of affective disorders, and type of surgery, which implies that factor scores can be used to compare these groups. The lesser fit of the model by surgery type is consistent with previous literature that even lesser surgeries can result in significant pain and it it is likely that individual factors have a greater impact than nociceptiva burden of surgical procedures in the experience of postoperative pain and treatment outcomes.13 Although previous studies have shown that satisfaction is greater in older patients,26 Jaipaul and Rosenthal showed that this factor varied with health status, so that older adults (patients older than 65 years) with poor health status report less satisfaction with treatment compared with older adults in good physical condition.15 That could explain the higher perception of care by the younger sample in our results because our population study came mainly from tertiary care hospitals that treat older people with poor health status. Our raw scores do not differ with the presence or absence of previous chronic pain, which is in agreement with previous studies showing that only previous severe chronic pain is related with worst postoperative outcomes.20 Opposite to results in Yang metanalysis,27 patients with obesity and history of affective disorders had similar raw scores in the 3 factors and were not predictors of would have liked more treatment. As expected, current smoking had lower raw scores in adverse events, mainly by the decreased risk of nausea,2 but similar raw scores in pain intensity and perception of care.When patients are grouped by age, the scores of the younger half of the sample are higher in intensity and interference, adverse effects, and perception of care. Gerbershagen et al. had already shown that young patients have greater postoperative pain regardless of the type of surgery.Would have liked more pain treatment is used to validate the predictive capacity of the questionnaire, under the assumption that wanting more pain treatment is an indirect but specific measure of poor pain control. Our analysis shows the probability of liking more pain treatment increases with the intensity and interference score and decreases with the perception of care score. This agrees with Schwenkglenks et al.24 study results that showed that satisfaction with pain treatment was associated with 3 items: more pain relief, greater participation in the treatment of pain, and no desire to have received more treatment. As expected, intensity and interference score and adverse effects were also related to high opioid consumption.2518 The IPO focus on postoperative pain, which is corroborated by its factor structure (the explained variance by intensity and interference factor in the Rothaug study is 36%). However, current trends derived from fast track and enhanced surgery protocols9 focus on the quality of postoperative recovery, especially the patient's early ability to move, which depends on other factors additionally to pain outcomes. Studies are needed to test the IPO validity in this new paradigm. Another limitation of the study is the absence of important variables related with the pain construct, such as sleep difficulties, degree of catastrophizing, and patient resilience as well as lack of presenting treatment data, such as type, doses, and combination of pharmacological and nonpharmacological treatment. Items factor loading depend on outcomes distribution, so pain treatments that significantly influence patient outcomes could have altered the present results.The main limitation of this study is the analysis of cross-sectional data, which did not allow to study the temporal reliability of the IPO measures, such as test–retest analysis. Other psychometric validations of the IPO, such as acceptability, responsiveness, divergent validity, and feasibility, were already proved in Rothaug study, so they were not analyzed here. The overlap of the sample with the previous validation study is a limitation, although CFAs are statistical hypothesis tests that evaluate if the data fit a hypothesized structural model (in this case a 3-factor structure model). Thus, the CFA is now sustained as the rational procedure used for the elaboration of the IPO questionnaire. Voluntary participation in the PAIN-OUT study makes the sample representative only of patients who attend public university hospitals. Characteristics of patients from other populations in Spain could modify the responses to the questionnaire and its factor structure.17The main strengths of our study are the large sample size, the inclusion of heterogeneous patients, and the use of MGCFA procedures to assess structure invariance by variables strongly related to pain. It is the first time that the IPO is conceptualized as a sum of scores in its main factors, which can serve as a global outcome analysis tool. Low scores in pain interferences and adverse effects with high scores in perception of care would indicate optimal quality of care.The total factor scores also allow simpler comparison between centers and procedures and could become an improvement tool in the quality of postoperative pain management.Further studies will be needed to increase the convergent and divergent validity of the questionnaire with other measures related to postoperative pain and recovery from surgery.24In conclusion, the study confirms the 3-factors structure of the IPO questionnaire in the Spanish population attending public university hospitals, its invariance by sex, age, previous chronic pain, and type of surgery, and serves as a proof that the sum of the scores of the factorial structure predicts would have liked more pain treatment, a key aspect in patient satisfaction, along with the ability to participate in treatment decisions and a sense of providers caring for them.The authors have no conflicts of interest to declare.http://links.lww.com/PR9/A96.Supplemental digital content associated with this article can be found online at


Previous studies have suggested that patients with psychotic or mental disorders are relatively pain insensitive, resulting in difficulties in the diagnosis of acute intra-abdominal diseases requiring emergency surgeries. We aimed to evaluate whether central nervous system (CNS) or mental disorders are associated with perforated appendicitis in patients with acute appendicitis.We conducted a population-based case-control study using Taiwan's National Health Insurance Research database. Patients aged >18 years who had been hospitalized with a diagnosis of acute appendicitis between 2000 and 2013 were identified. After 1:1 matching for age and sex, 2792 patients with perforated appendicitis (case group) and 2792 patients with nonperforated appendicitis (control group) were included. CNS disorders, mental disorders, pain control medication, and several comorbidities were analyzed for the odds of appendiceal perforation with 95% confidence interval (CI) using the multivariable logistic regression model.P = .009) and 4.8 for schizophrenia . Other factors, such as other CNS disorders, comorbidities, and pain control medication, were not associated with the risk of perforated appendicitis.Schizophrenia and dementia were associated with a high risk of appendiceal rupture in patients with acute appendicitis, with an adjusted odds ratio of 2.01 for dementia (95% CI: 1.19–3.39, Dementia and schizophrenia are associated with perforated appendicitis in patients with acute appendicitis. This might be owing to altered pain perception, difficult symptom expression, and delayed hospitalization. Further studies are still needed to determine the underlying mechanism and confirm the causality. Usually, the treatment is based on whether the appendicitis is perforated. For example, nonoperative treatment is reasonable when ruptured appendicitis is complicated with peri-appendiceal abscess. Generally, the perforation rate in acute appendicitis is approximately 13% to 20%, and it may be owing to delayed presentation. Perforated appendicitis accounts for more mortality and morbidity than those without.Acute appendicitis is the most common abdominal surgical emergency in the world, In that study, the investigators reported their experience with 5 critical ill patients who had chronic schizophrenia and decreased pain perception; the lack of signs and symptoms in these patients resulted in delayed abdominal surgery. Moreover, pain insensitivity may also cause delay in the presentation of acute appendicitis, resulting in perforation. In a retrospective cohort study, it was observed that appendiceal perforation was more frequent in patients with schizophrenia than in controls. Another population-based retrospective study suggested that schizophrenia is associated with a 2.83 times increased risk of ruptured appendix in those who were hospitalized for appendicitis. In addition to psychiatric disorders, altered pain perception is also common in older patients owing to cognitive impairment , medication for chronic pain and multiple coexistent diseases. Hence, the precise diagnosis of acute appendicitis is also challenging in the elderly. Therefore, the incidence of perforated appendix is high in them.,14 However, the association between the risk of perforated appendicitis and central nervous system (CNS) disorders has not been clearly reported. In light of existing evidence, we hypothesized that dementia and schizophrenia are associated with perforated appendicitis in patients with acute appendicitis. Here, we present data on a nationwide population-based case-control study that analyzed the association between ruptured appendicitis and mental or CNS disorders.Previous study reports indicate that patients with psychotic disorders such as schizophrenia are relatively pain insensitive which often leads to difficulties in the diagnosis of acute intra-abdominal diseases requiring emergency surgeries.22.1Taiwan launched its single-payer and mandatory-enrollment National Health Insurance (NHI) program in 1995. More than 99% of the Taiwanese are covered by the NHI program. All outpatient, inpatient and emergency services are covered by the NHI. This study was conducted by using Longitudinal Heath Insurance Database (LHID). The LHID, a subset of the Taiwan's NHI Research Database, contains data from 1 million people who were randomly sampled from the 23.8 million NHI beneficiaries for research purposes by the National Health Research Institute of Taiwan. The diagnostic codes used in LHID were from the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). To protect patient privacy and data security, personal identifiers in the LHID were encrypted before the National Health Research Institute released the database. This study was approved by the Research Ethics Committee of China Medical University and Hospital in Taiwan (CMUH-104-REC2-115). Informed consent was not required for this observational study according to our institutional guidelines.2.2The case and control populations were obtained from the LHID. Our study population included adult patients aged ≥18 years who were hospitalized (index admission) owing to acute appendicitis  between 2000 and 2013. The patients with perforated appendicitis  were classified as the perforated appendicitis group (case group) and the patients with nonperforated appendicitis  were classified as the control group by 1:1 propensity score matching for age and sex.2.3We identified whether patients had been diagnosed with mental or CNS disorders before the hospitalization for acute appendicitis. Patients were categorized as having a mental or CNS disorder if there was at least 1 inpatient or 2 outpatient records as diagnosed by a neurologist, neurosurgeon, or psychiatrist before the index admission. CNS disorders included dementia , Parkinsondisease (ICD-9-CM 332), cerebrovascular diseases (ICD-9-CM 430–438), and other CNS disorders . Mental disorders included schizophrenia (ICD-9-CM 295), affective disorder (ICD-9-CM 296), and other mental disorder .2.4Potential confounders such as diabetes (ICD-9-CM codes 250), hypertension (ICD-9-CM codes 401–405), ischemic heart disease (ICD-9-CM codes 410–414), chronic obstructive pulmonary disease (ICD-9-CM codes 490–496), chronic kidney disease (ICD-9-CM codes 580–589), cirrhosis (ICD-9-CM codes 580–589), and malignancy  were retrieved. Those comorbidities were defined as a disease diagnosed in at least 1 inpatient record or 2 outpatient records within 1 year before the index admission. Baseline medication for pain control was defined as a drug that had been prescribed within 3 months before the index admission, including non-steroidal anti-inflammatory drug (NSAID), opioids, and steroids by prescription code in National Health Insurance Research Database (NHIRD). Monthly income, urbanization, hospital geography, and hospital accreditation were also considered. Income was categorized into 3 levels  based on the income-related NHI premiums. Urbanization levels of residence were categorized into 4 levels (level 1 indicated the most urbanized areas and level 4 the least urbanized).2.5t-tests and categorical variables were compared by χ2 tests. The logistic regression model was used to calculate the adjusted odds ratio (OR) with 95% confidence interval (CI) for risks of perforated appendicitis associated with mental or CNS disorders. The multivariate logistic regression model was performed with adjustments for all potential confounding factors as listed in Table P < .05 was considered statistically significant.Continuous variables were compared using 3P = .001) and dementia  between the 2 groups.Table P = .005) and 2.01 in dementia . However, subjects with other mental disorders were associated with a reduced risk of appendiceal rupture . Other factors, such as affective disorder, Parkinson disease, stroke, and other CNS disorders, were not associated with a risk of perforated appendicitis. All other baseline comorbidities and medication for pain control were not associated with an increased risk of developing perforated appendicitis.Table 4Data in this nationwide population-based case-control study indicate that schizophrenia and dementia were associated with an increased risk of perforated appendicitis among patients with acute appendicitis. Other factors, such as affective disorder, Parkinson disease, stroke, and other CNS disorders, were not associated with the risk of perforated appendicitis. In addition, all other baseline comorbidities and medicine usage for pain control were not associated with an increased risk of developing perforated appendicitis.,10 One retrospective cohort study included 62 patients with schizophrenia and 200 without schizophrenia requiring appendectomy (N = 1821). The adjusted OR for perforation was 4.87 (95% CI: 2.33–10.2) for schizophrenia, 2.18 (95% CI: 1.12–4.27) for delayed presentation and 3.35 (95% CI: 1.51–7.45) for age > 55 years. Another population-based retrospective study using NHI data in Taiwan also found that patients with schizophrenia have a 2.83 times higher risk of having ruptured appendicitis . Age was also found to be a contributor to perforated appendicitis. However, in that study, there was no significant difference with respect to perforation risk in affective psychoses or other mental disorders compared with controls. However, there were no sufficient data for other factors influencing pain sensitivity or cognition function in these previous studies. Our study evaluated other related factors such as stroke, Parkinson disease, dementia, and other CNS disorder which can affect pain sensitivity or cognitive function. The use of medication for pain control was also analyzed and was not found to be associated with ruptured appendicitis.Previous studies have demonstrated the possible association between perforated appendicitis and schizophrenia.,15,16 Our study revealed a 4.8 times higher perforation rate in the case group than that in the control group, which is similar to that reported by a previous retrospective study. In addition to schizophrenia, we found that dementia also has a significant association with perforated appendicitis , which may explain the increased risk of perforated appendicitis in the elderly reported by previous studies.,14,17 One explanation for these data is that elderly patients, particularly those with cognitive dysfunction such as dementia, may have difficulty describing their symptoms which could mask the severity of the appendicitis. Pain threshold also increases with age which can result in delayed hospitalization and may also contribute to the high risk of perforation in acute appendicitis.,19 In addition to ruptured appendix, previous investigators have reported several cases of schizophrenia patients presenting pain insensitivity of painful medical condition like peptic ulcer, peritonitis, acute abdomens, perforated bowel, and compartment syndrome, which resulted in tragic outcomes such as late surgical attention, misdiagnosis, and delayed treatment. Of note, in medical students and doctors, there are more stigmatizing attitudes toward schizophrenia patients about dangerousness, unpredictability, and even desire for social distance. This stigmatization may be a barrier for patients with mental disorder to receive the treatment they need.Altered pain perception and high pain thresholds in patients with schizophrenia may result in delayed emergent operation for appendicitis, resulting in perforation.,23 For example, dysfunctions of opioid receptor- and N-methyl-D-aspartate receptor-mediated neurotransmission in CNS have been suggested to participate in the increase in pain threshold in patients with schizophrenia. Additionally, age-related loss in the structure and function of the peripheral and CNS pathways has been implicated in the reduced pain sensitivity in patients with dementia. Furthermore, the inability to successfully communicate pain in these patients may be a contributing factor.Pain perception involves peripheral afferent pathways and CNS processing of nociceptive signals. The mechanisms underlying the insensitivity to pain in schizophrenia or dementia are largely unknown, although some notions have been postulated.The present study had some limitations that should be addressed. Some information that could be relevant, such as time of admission after the development of symptoms, lifestyle of the subjects, patient's clinical presentation, vital signs, laboratory test results, and imaging study reports could not be accessed using the claims-based data, and, therefore, could not be controlled or adjusted. Additionally, we were also unable to interview patients to confirm the diagnosis and obtain information regarding their pain perception. Further studies overcoming these issues are required.In summary, this population-based case-control study identifies schizophrenia and dementia as risk factors for perforated appendicitis in patients with acute appendicitis. This association may be due to the possibility that patients with psychotic or mental disorders are relatively pain insensitive, resulting in difficulties in the diagnosis and surgical treatment of acute appendicitis. The accuracy of prompt diagnosis of appendicitis remains challenging in such specific populations. Future prospective large-scale studies are still necessary to explore and confirm this clinical issue. Further, studies are also needed to determine the factors that affect pain insensitivities and to understand the underlying mechanisms.Data curation: Hsiang Chi Wang, Jen Hung Wang.Formal analysis: Hsiang Chi Wang, Jen Hung Wang.Investigation: Huang Ren Lin, Hsin Han Lu.Methodology: Hsiang Chi Wang, Jen Hung Wang.Supervision: Jen Hung Wang.Validation: Jen Hung Wang.Writing – original draft: Huang Re Lin, Hsin Han Lu.Writing – review & editing: Huang Ren Lin, Hsin Han Lu.


Background: Dizziness and pain are common complaints that often appear concomitantly, with or without a causal relationship. However, these symptoms might maintain and exacerbate each other and other co-morbidities. Therefore, adequate rehabilitation may have to include an expanded focus on other deficits and preconditions, especially in older adults and in patients.Objective: To understand how frequently vestibular dysfunction coincided with medical conditions and aging, we studied two categories: Study 1: patients referred to a vestibular unit and Study 2: senior members in a fitness association.Method: Study 1: 49 patients  seeking health care for balance disorders and vestibular deficits were asked in questionnaires about their perception of dizziness and pain, and emotional and functional strains. Study 2: 101 senior members in a fitness association , were assessed for vestibular and balance deficits and for any co-morbidities. The participants were monitored for falls for 12 months after the initial assessments.Result: Study 1: Co-morbidity often existed between dizziness and pain (65%). The patients reported high emotional and functional strain related to their dizziness and pain. Patients older than 60 years reported longer durations of pain (p ≤ 0.028) but less emotional strain (p = 0.036), compared to younger patients. Study 2: 84% of the participants had a vestibular impairment, often without noticing any symptoms. Furthermore, 40% reported cardiovascular illnesses, 12% musculoskeletal disorders, and 63% reported other medical conditions. Forty-two percent experienced falls within 1 year after the initial assessments (thereof 42% in the group with vestibular deficits and 38% in the group without vestibular deficits).Conclusion: To enhance and preserve postural control, both in patients with vestibular deficits and in older adults, we suggest an expanded clinical perspective. Hence, we recommend detailed examinations of the vestibular system but simultaneously probing for possible co-morbidities. Since aging often entails deterioration of multimodal processes related to maintained mobility and postural stability, our results add focus on the importance of addressing balance disorders together with additional medical conditions. Remaining in equilibrium with adequate adjustments during locomotion and movement requires a constantly ongoing feedforward and feedback postural control system . This syThe peripheral vestibular sensors can be considered as part of a multifaceted sensorimotor control system with several interacting and interfering entities. However, the normal aging processes cause over time increasingly larger multisensory deficits and multimodal deterioration within the postural control system, which impair the ability to produce accurate postural adjustments , 6. SomeA fall is an obvious and severe outcome of dizziness or loss of balance . The cloThese studies aimed to identify occurrences of some co-morbidities related to vestibular impairments and dizziness. More specifically, we wanted to investigate the co-existence of dizziness with other commonly occurring ailments, and especially with musculoskeletal pain. We also wanted to analyze how common vestibular dysfunction and impaired postural control  is in a population of still physically active older people.The study conforms to the standards set by Declaration of Helsinki, 2004 and was approved by Regional Ethics Review Board , Lund University, Lund, Sweden. All subjects participated voluntary and provided written informed consent before taking part in the study. The data collection used in study 1 is an extraction from an already published article from our research group, the extracted data here categorized and analyzed to determine co-morbidities .n = 15); (2) subjects <60 years of age (n = 34), and (3) the youngest 15 subjects in the population (n = 15). Results from the total study population has been partly reported, with allowance of extraction for the purpose of the present paper ) 2.0], consecutively referred to a tertiary referral center for examination of vestibular deficits and balance dysfunction. To be included the patients had to be adult, conceding to be a part of the study, being able to understand and communicate, and fill out the required questionnaires. The patients thus had a variety of diagnosis with symptoms of dizziness or perceived balance impairment. Study questionnaires were sent to the patients 2 weeks before the visit and collected at the visit. Patients that subsequently failed to return the questionnaire were excluded. The population was divided into three subgroups for comparisons; (1) subjects ≥60 years of age  questionnaire and a custom-made questionnaire detailing the properties of pain, dizziness, and occurrence of trauma/accident, considered by the patient to be related to their symptoms.This questionnaire included 25 questions related to the dizzy symptoms, assessing perceived handicap and impact on quality of life –25. In tThis questionnaire comprised eight questions, that queried intensity and duration factors related to dizziness and if present, of a pain  15). Fo. Fo15). n = 85) and subjects without vestibular deficits (n = 16). The subjects in the two categories had similar mean age (75.1 vs. 74.8 years) and both categories were dominated by females (Table 5).The participants were senior members of a Swedish fitness association who were invited to a balance workshop. The workshop was repeated at three different times to allow all volunteering subjects to attend. The inclusion criterion was that the subject should be an active participant in a fitness association, and by that indirectly, having an independent and physically active lifestyle. Subjects that failed to return the fall incident dairies during the 12-months observation period were excluded. In total, 150 persons attended the workshops. Out of these, 113 accepted to participate in the study. The 101 participants  who performed all testes and returned at least one fall diary were included in this study. After performing a series of vestibular assessments the population was divided into two categories, subjects with vestibular deficits  with the headshake test, Dix-Hallpike test , and heaThree screening tests of the vestibular function were performed . The eyeVestibular asymmetry was assessed by the headshake test, where the tested person was lying supine and the examiner shook their head from side to side for 15 s at ~2 Hz.Benign paroxysmal positional vertigo for the posterior and anterior canals were assessed by the Dix-Hallpike test. The tested person sat on an examination table, with their head turned about 45° to the left or right. The examiner thereafter moved the patient down into a supine position, with the patient's supported head leaning back about 30 degrees. The test was considered positive if nystagmus and vertigo occurred .For assessing hypofunction in the angular vestibulo-ocular reflex, the head impulse test was used. The tested person was asked to focus the gaze on the examiner's nose, and the examiner rotated the patient's head slowly from side to side. The examiner then turned the head rapidly about 20° to one side. The test was repeated randomly to each side. The test was considered pathologic if the tested person was not able to keep their eyes focused on the target, but responded with a corrective or compensatory saccade , 30.Balance was assessed by the TUG, TUGcog, and TUGman. In TUG, the tested person was instructed to stand up from a chair, walk in a fast but safely pace three meters and cross a line marked on the floor, turn around, walk back to the chair, and sit down . In TUGmAll participants were given a falls diary booklet at the workshop, in which the participant noted falls during a 12-months period. The participants were instructed to detail in the diary the number of times they had fallen and describe the situational characteristics of the incidents associated with the falls. Every third month during the 12-months follow-up, a new diary was sent home by ordinary mail, together with a pre-paid envelope, which the participant used for returning the filled-in diary. The falls was categorized according to a classification system from St. Louis, Older Adult Service and Information System (OASIS) .U (two-tailed) analysis or the Pearson's Chi-square test when appropriate (p < 0.1) are presented in the figures and marked with bold text in the tables.Our initial analysis revealed that patients referred to a vestibular unit often displayed symptoms that seemed related to their age above and below 60 years of age. Therefore, to reveal better any age effects, data from the subjects ≥60 years were compared with all subjects below 60 years of age, and a subgroup of the 15 youngest subjects in the population. Moreover, pain in various parts of the body was also very common and the patients reported that their symptoms might be associated with an accident they had experienced . The rolropriate . In the ropriate . P-valuep-value set to 0.05 (two-tailed), our study would require n = 14 subjects to reach a power value of 0.8 for this parameter category , our study would require n = 10 subjects to reach a power value of 0.8 for this parameter.Using the statistical package GPower 3.1™, sample size analyses of parameter categories, such as DHI revealed an effect size of 1.1, which shows that with the category . The samU (two-tailed) analysis or the Pearson's Chi-square test when appropriate  are marked with bold text in the table.Non-parametric statistical methods were used since distribution tests with Kolmogorov-Smirnov and Shapiro-Wilk methods revealed that some of the datasets did not have a normal distribution profile and that normal distribution could not be obtained by logarithmic transformation. In the analyses, nificant . BonferrIn study 2, measures of step time was also performed, using a wearable device. Step time was used for calculation of power. Expecting 50% more falls among persons with a variance in step time of ≥2.0 ms, and the level of significance set at 0.05, a total of 60 participants would be necessary to reach a power of 80%.The statistical analyses were performed with SPSS 26.0 software  and the power analysis was performed with GPower 3.1™.The patients with balance disorders showed signs of physical, emotional and functional strain, irrespectively of age. In the total DHI score, 19 of 49 subjects (39%) reported severe handicap; 9 of 49 subjects (18%) reported moderate handicap, whereas 14 of 49 subjects (29%) reported mild handicap. A large proportion of the patients, 65.3% (SEM 6.9), presented co-morbidity with pain to the levels that it influenced daily life. Another co-morbidity factor was that 24.5% (SEM 6.2) of the subjects reported that they believed some of the symptoms they experienced were related to a history of an accident.p = 0.054), and significantly lower than the youngest age category (p = 0.036), suggesting less emotional strain. Pain symptoms were commonly reported in all populations and this did not differ significantly between the older and younger populations. However, the older population reported significantly longer pain duration than the <60 years category (p = 0.023), and the youngest age category (p = 0.028). Finally, the dizziness duration tended to be longer in the older population than in the youngest population (p = 0.063).Females were overrepresented in all age categories, but the gender distribution was not significantly different between any of the categories . The oldp = 0.082). Moreover, the youngest population tended to report more pain in the neck/shoulder region (p = 0.065), but significantly less pain in the arms (p = 0.032) and also a tendency of less pain in the legs (p = 0.099) than the older population.The population <60 years tended to report pain more often in the upper torso region compared with the older population , though p = 0.013) (p = 0.004) and in the DHI sub-scales DHI_Emotional (p < 0.001) and DHI_Functional (p = 0.011). A significant number of the patients that reported pain had a history of an accident (p = 0.004).The females suffered more often from pain than males (= 0.013) . The patIn the patients suffering from any kind of pain, the most common location for pain were the head (56.3%), the neck/shoulder (87.5%), the back (65.6%), and the legs (43.8%) .p = 0.054) (p = 0.004).Females tended to more often have experienced an accident than males (= 0.054) . The patp = 0.013) and neck/shoulder (p < 0.001) and tended to have more often pain in the back (p = 0.055) compared with patients that had no history of an accident (The patients reporting that they had an accident in their history had significantly more often pain in the head (accident .n = 85), most of the subjects had pathological headshake nystagmus (90.6%) and pathological head impulse responses (46.4%)  . A smallEven if many of participants reported that they had no illnesses, many of them used some kind of medication. Therefore, the categorization of illnesses was based on both reported illness and reported medication. In the total population, 40% reported cardiovascular illnesses, 12% musculoskeletal disorders, and 63% reported other types of illnesses that affected daily life. The frequencies of illnesses were very similar in both categories of vestibular deficits and without vestibular deficits. Cardiovascular illnesses were common in both categories, 38.8 vs. 43.8%. Severe musculoskeletal disorders and other illnesses were also common in both categories (10.6 vs. 18.8%) resp. (28.2 vs. 12.5%). Some subjects in both categories reported more than one illness (14.1 vs. 18.8%).The mean values and standard error of mean for age, the TUG, TUGman, and TUGcog tests and the results for health status and vestibular tests are shown in We found that patients with dizziness also commonly report musculoskeletal pain and that co-morbidities between dizziness and pain add psychological distress. In addition, older subjects, healthy enough to participate in physical activities, frequently had asymptomatic vestibular deficits. Almost half of these physically active older people experienced one or more fall incidence during the following year.Although both dizziness and pain are common in a general population, the concurrent appearance of these two symptoms might suggest an interrelationship as well as an additional burden for the individual. The patients with pain demonstrated significantly higher levels of perceived handicap of their dizziness, and thus, that this had consequences on their perceived quality of life compared to patients that did not report pain. Older patients stated significantly longer pain duration and they reported more pain in their lower extremities compared to the younger population, who had more pain in the neck/shoulder and torso regions .In patients that reported pain, 38% also reported a history of an accident the patient themselves thought was the origin of the pain. These patients had significantly more often issues with pain in the head and neck/shoulder regions and reported more often back pain . Pain inThe high frequency of reported pain conditions in lower extremities, the neck and the shoulder regions in this study group of dizzy patients, highlight the importance of asking patients about any pain conditions and history of trauma.Since aging often entails deterioration of multisensory and multimodal processes related to maintained mobility and postural stability, our results add focus on the importance of paying attention and taking direct actions when balance disorders occur together with pain and other medical conditions. Especially when dizziness occurs together with pain in the neck/shoulder regions and in the lower extremities, the symptoms might interact and maintain or even enhance each other. To some extent, the balance deficits may be compensated for, but the adjustment options might be fewer due to pain related impairments. Thus, the functional loss may become more prominent, with reduced physical function and thereby also a loss of postural stability –13.per se is regarded as one important factor for preserved postural stability  of the older subjects active in a fitness association demonstrated vestibular asymmetry or other balance function disturbances. Most of them were not aware of such dysfunctions. That said, the study participants all had responded to an invitation to take part in a workshop about balance, which might suggest that at least some of them had a specific interest in such a topic. Thus, one may speculate that this interest might be instigated by them having experienced instability and balance disturbance. If that was the case, that would explain the proportionally very high amounts of vestibular asymmetry in the studied group compared to other populations 4% of the, 46. On More than half of the group reported impairment related to other medical conditions, which highlight the importance to evaluate the person's entire state of health regarding their ability to maintain postural control. Vestibular dysfunctions are common in the older population and together with physiological changes and multi-morbidity it implies a risk of hazardous events, such as falls . KristinBoth sub-studies were explorative, carried out independently and performed in two different contexts. However, they both addressed co-morbidities to vestibular impairments and dizziness.Both study 1 and study 2 included subjective self-reported data. Thus, in study 1 questionnaire answers and reports of pain might be skewed by, e.g., subjective exaggeration of symptom severity. However, a recently published study with similar approach and scope as in study 1 largely confirm our findings . Study 2In study 2, the commonly used and simple to perform TUG test was utilized to make a primary assessment of postural control, as some studies suggests that this method can determine fallers from non-fallers , 49. An The findings highlight some of the most important factors for our ability to be active and in good health at old age. A good body balance, good postural alignment, and preserved muscle strength are considered to be protective factors for maintain an active lifestyle in aging. These factors also coincide with good quality of life . Since mIn summary, based on the clinical implications of our results, together with previously acquired knowledge, we recommend health care practitioners to always ask for, and consider the co-morbidities that often coincide with dizziness. Pain should be considered a common co-morbidity, of importance to address both for optimal vestibular rehabilitation and for training postural control. Having a history of an accident/trauma may also be a contributing factor to dizziness, pain, and sensorimotor deficits. When performing rehabilitation, the exercises should promote a holistic approach of maintaining healthy muscular and biomechanical function in all intersegmental levels, as well as to facilitate optimum use of integrated sensory information from all sensory sources, i.e., vision, vestibular, mechanoreceptors, and proprioceptors. Older adults may be more prone to suffer from vestibular impairment, and should be diagnosed and rehabilitated accordingly.The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Regional Ethics Review Board , Lund University, Lund, Sweden. The patients/participants provided their written informed consent to participate in this study.E-MM, EE, MM, and P-AF conceived the study design. E-MM, EE, and MM executed the data collection procedures. E-MM, EE, MM, AH, and P-AF analyzed and interpreted the results and contributed to the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The aim of this study was to investigate whether statistically significant differences exist regarding pain and the impact on oral quality of life of orthodontic treatment. A conventional brackets system was compared with low-friction brackets. A total of 90 patients  were chosen for this randomized clinical trial. Pain was assessed at 4, 8, and 24 hours and 2, 3, 4, 5, 6, and 7 days after the start of treatment using the McGill Pain Questionnaire. Oral health-related quality of life (OHRQoL) was assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire. Oral quality of life was assessed at one month, with patients with low-friction brackets describing lower levels of pain. The patients with conventional brackets indicated a worse impact on their quality of life compared to the group with low-friction brackets. Statistically significant differences were found between the groups, with maximum pain observed between the first 24 and 48 hours, and the values of minimum pain are reached after 7 days. The pain and impact on oral quality of life was statistically worse in patients with conventional brackets compared to patients with low-friction brackets. The type of bracket system used was therefore shown to influence patients’ perceptions of pain and impact on their OHRQoL.  Orthodontics is a dental specialty that has rapidly developed over recent decades. It deals with the correction of dental malocclusions and maxillary bone alterations through the application of forces that produce tooth movement . During According to several studies, approximately 90% to 95% of patients receiving orthodontic treatment experience pain during the first weeks of treatment ,4. This Pain is an undesirable consequence of this orthodontic treatment. The pain described by patients may appear spontaneously, due to the force applied to the teeth in order for them to move, or as a consequence of functional processes, such as chewing . This paGiven that orthodontic pain in orthodontic patients is due to the application of forces that generate pressure, ischemia, inflammation, and edema in the periodontal tissues, some clinicians use lubricants to reduce friction and thus the perceived pressure on teeth . OrthospThe perception of pain depends on a person’s individual characteristics, such as age, sex, threshold of individual pain, stress, cultural differences, the magnitude of the force that is applied during treatment, and the emotional state of the patient. At present, there are only a few published studies concerning the impact on the oral quality of life of patients undergoing orthodontic treatment. However, the reports that do exist suggest that orthodontic treatment, which has an important psychosocial component, requires measures to assess the oral quality of life ,11,12.The purpose of this study was to analyze whether there were statistically significant differences regarding the perception of pain in the first seven days of orthodontic treatment and the impact on oral quality of life during the first month of orthodontic treatment. In addition, a conventional brackets system was compared to low-friction brackets and low-friction brackets alongside the use of lubricating gel (Orthospeed®). The null hypothesis was that the prevalence and severity of pain and the impact on oral health-related quality of life would not differ among the groups of patients.The research project of this randomized clinical trial was approved by the Bioethics Committee of the University of Salamanca (USAL_16/060). The study followed the guidelines established by the Helsinki Declaration for research involving human subjects, as well as the CONSORT guidelines. The participants were informed about the examination procedures and assured regarding confidentiality of the collected information. Only those who gave written consent were included in the research.Sample size calculation was performed using the Raosoft online sample-size calculator . With a margin of error of 5% and a confidence level of 95%, the target sample size was determined to be 90 patients, including 10% dropout. Previously published studies were considered when calculating the sample size ,11. All This randomized clinical trial consisted of a total of 90 participants and was designed following the CONSORT guidelines . The sample was divided into three groups, with each group consisting of 30 patients. The first group (CON group) consisted of patients who were fitted with conventional fixed-type multibrackets , the second group (LF group) was composed of patients who were fitted with low-friction fixed multibrackets , and the third group (LFO group) consisted of patients who were fitted with low-friction fixed multibrackets  and used Orthospeed®. In the treatment protocol, all of the employed brackets had 0.022" slots. The initial treatment arc was 0.014" super-elastic nickel-titanium . Brackets were ligated with 0.12-inch elastomeric ligatures (G&H Orthodontics). The patients were examined after four weeks to ensure the brackets were intact. After bracket bonding, archwires were inserted and ligated to all teeth in both the maxillary and mandibular arches. The archwire was cut distal to the molar tube without cinching back. During the single-blind study, the allocation of the bracket type of brackets was concealed from the participants but not the clinician. -Permanente dentition and aged between 18 and 40 years old;-No previous orthodontic treatment;-No craniofacial anomalies;-No missing teeth, with the exception of third molars;-Dental bone discrepancy between −1.5 and −7.0 mm in both arches; and-Skeletal Class I or II malocclusion (ANB 0° and 5°) .The inclusion criteria were as follows: -Patients requiring tooth extractions;-Mild or high dental crowding (between −1.5 and −7.0 mm);-Patients who are not in a period of dental eruption;-Significant physical or mental impairment;-Patients with orthodontic-surgical treatment;-Chronic use of analgesic, antidepressants, and/or anticonvulsants medications;-Patients with previous pain-related pathology or disease ;-Dental caries;-Pregnancy; and-Patients with auxiliary orthodontic appliances.The exclusion criteria were as follows:No bite planes, lingual arches, or intermaxillary elastics were placed and no dental extractions were undertaken during the study period. Similar oral hygiene and appliance maintenance instructions were given to the four groups. Patients who declined to participate in the study were excluded from the sample. Patients who presented with periodontal pathology (gingivitis) were treated before starting orthodontic treatment to ensure that all patients began their orthodontic treatment with good oral health.http://www.randomizer.org/form.htm), namely, conventional fixed-type multibrackets , low-friction fixed multibrackets , and low-friction fixed multibrackets  with Orthospeed®  use. Bracket bonding, archwire insertion, and orthodontic treatment were performed by one nonblinded experienced operator between June and December 2019. Crowding was calculated according to dental bone discrepancy.In total, 90 patients were enrolled to increase the power of the study and compensate for possible dropouts. These patients were randomly divided into three equal treatment groups by using a randomization program  according to the McGill Pain Questionnaire from 0 to 10, with the terms "absence of pain" and "maximum pain" as endpoints. This scale evaluated the pain perceived by the patient at 4 hours (T1), 8 hours (T2), 24 hours (T3), 2 days (T4), 3 days (T5), 4 days (T6), 5 days (T7), 6 days (T8), and 7 days (T9) after the start of the treatment. One month after treatment, the patients completed the Oral Health Impact Profile-14 questionnaire (OHIP-14) to measure the impact on oral quality of life. The OHIP-14 questionnaire used in this study was previously developed by Slade (1997) as a shorter version of the OHIP-49 questionnaire introduced by Locker and Miller (1994). The OHIP-14 questionnaire was used to measure oral health-related quality of life; the Spanish version of this questionnaire was validated previously [In this questionnaire, the participants were asked how often they had experienced impact with regard to each of the 14 items, and the responses were set on a 5-point Likert scale . This instrument was conceptually divided into seven subscales  based on Locker’s theoretical model of oral health .Impact was measured by totaling up the number of items recorded as occasionally or more often, thereby obtaining a quantitative variable that reflected patient wellbeing. Each domain was composed of two items, thus the impact score in each domain ranged from 0 to 2.n, %) of the categorical variables and the means and standard deviations (mean ± SD) of the quantitative variables were used to describe the relevant variables in the sample. Descriptive statistics  were calculated using SPSS v-20 . The differences between the groups were analyzed using the ANOVA test with post-hoc Bonferroni correction for the quantitative variables. Pearson correlation coefficients were calculated to assess the linear relationships between the quantitative variables, respectively. The level of significance was set at 0.05.The sample distribution (n = 30). A CONSORT diagram showing the flow of the patients through the study is given in In total, 102 patients were screened from the Dental Clinic of the University of Salamanca during 2019. Twelve patients were excluded as they did not meet the inclusion and exclusion criteria, with a total of 90 patients meeting the screening criteria. All 90 patients consented and were randomly assigned to one of the three treatment groups by random tables, with equal numbers in each group  were men and 61.1% (55 patients) were female; this distribution was similar throughout all groups . p < 0.05). The patients with the conventional brackets exhibited had the highest mean value with respect to the level of pain during the entire first week after treatment (3.5 ± 2.4). In comparison, the group of patients with the low-friction brackets using Orthospeed® described the lowest level of pain on average (1.3 ± 1.9) for the same time period. This trend was observed throughout the entire follow-up period.Statistically significant differences were found among the different groups throughout all assessment time points (p < 0.01) after the start of the study, with the patients with low-friction brackets, regardless of Orthospeed® use, indicating that their maximum level of pain occurred within the first 24 hours  (p < 0.01). From this peak, the level of pain gradually decreased until day 7 in all three groups .In addition, a trend was observed after analyzing the influence of gender on the level of pain perceived during the first seven days, as greater levels of pain were perceived by women. However, this result was not statistically significant , especiap < 0.05) were significantly higher than the low friction group using Orthospeed®  (p < 0.05). As determined by the OHIP-14 questionnaire, pain, psychological discomfort, functional limitation, and physical disability were the most commonly affected dimensions. The impact on the handicap dimension was zero throughout all three study groups.p = 0.03).Regarding ofthe possible influence of gender on oral quality of life, This randomized clinical trial aimed to evaluate whether two bracket systems  influenced patient pain perception and oral quality of life, as well as the effect of the use of a lubricating gel (Orthospeed®) on the same descriptors. The limitations of the present study could be due to the short follow-up period in relation to the duration of the orthodontic treatment.Published studies comparing low-friction Synergy® brackets with conventional brackets are based on in vitro investigations ,17,18. SIn this study, a significant discrepancy was observed between the pain caused by conventional brackets compared to low-friction brackets alongside the use of Orthospeed®. However, according to other authors, no statistically significant differences exist regarding pain between patients with conventional brackets and self-ligating brackets during the first week of treatment ,26,27. HIn recent years, several questionnaires were developed to assess patients’ oral quality of life levels. In this regard, the OHIP questionnaire was the most frequently used in published studies and was also the questionnaire used in this work ,31,32. This study showed that the level of oral quality of life was significantly better at 30 days of treatment in the group using Orthospeed® compared to the group who were fitted with conventional brackets . HoweverPain is the dimension that has the greatest impact on patients compared to the other dimensions of oral quality of life, as shown in The primary limitation of this study was the sample size of 90 patients (30 patients per group). Of the 90 patients, 55 were female and 35 were male. In daily clinical practice, the frequency of female orthodontic patients is higher compared to male patients, as females are generally more concerned about their dental appearance than males. According to previous studies, gender does not influence the pain described by patients during orthodontic treatment ,27,33,34To the best of our knowledge, this was the first randomized clinical trial reported in the literature, where the effect of a lubricating gel (Orthospeed®) and a conventional brackets system is compared to a low-friction bracket system to assess relative pain and the impact of orthodontic treatment on patients´ oral health-related quality of life. Future research could be directed to optimize the use of Orthospeed® in orthodontic treatment.The peak of maximum pain was reached between the first 24 and 48 hours, at which time it started to decrease until reaching minimum values on the seventh day. Pain and the overall impact on oral quality of life was statistically worse in patients with conventional brackets compared to patients with low-friction brackets who used the lubricating gel (Orthospeed®).


Background: An important motivation for adolescents and young adults to engage in aerobic exercise (AE) is to improve fitness, body composition and physical appearance. These parameters have an impact on bodily perception as conceptualized by the ‘body image’ (BI) construct. AE is known to have positive effects on pain perception, mood, and body image (BI). However, no study has hitherto investigated their interrelationship within one study. Methods: Participants were randomly assigned to an intervention group  or a passive control group . Frankfurt Body-Concept Scales (FKKS), Positive and Negative Affect Scale (PANAS), State and Trait Anxiety Inventory, warmth and heat pain thresholds , pain tolerance, and graded exercise test data from baseline (T0) and the end of the intervention (T6) were analyzed using a paired t-test (p < 0.05). Results: A significant increase in the BI dimension ‘physical efficacy’ was identified from T0 to T6, which correlated positively with PANAS Positive Affect Scale and HPT. Conclusion: Data in young adults undergoing AE indicate that changes in the BI sub-category ‘physical efficacy’ are closely linked with changes in positive affect and antinociception. These novel findings suggest that BI plays a role in antinociception and positive affect. Aerobic exercise (AE), either voluntary  or prescRegular AE has been shown to go along with small to moderate positive effects on BI ,20,21,22Research distinguishes between the independent concepts of positive and negative body image , which mMoreover, AE has positive effects on pain perception. Exercise-induced hypoalgesia (EIH), is a well-established psychophysical phenomenon that is thought to play a role in prevention and non-pharmacological management of chronic pain states. Experimentally, EIH can be elicited as acute local and/or remote heat or cold pain threshold changes on sensory testing, or by enhanced pain tolerance ,34,35,36Whether the biological and psychological concepts are mutually exclusive or rather interrelated remains unknown as no study, we are currently aware of, has measured the three components  within one single study design. Therefore, the purpose of the present study was to determine whether changes in BI concept predict exercise-induced changes in mood and pain perception and, if so, to unravel which subcomponent of the BI concept—‘self-acceptance of one’s body’, ‘physical efficacy’, or ‘health’—has a driving force. Hypothesizing differential downstream behavioral effects depending on (i) long-term PE (intervention group) or (ii) continued sedentary behavior (control group), our analyses of the BI questionnaire , were me‘RUNSTUD’ is a longitudinal AE intervention study of six months duration in which young (24.2 ± 4.2 years) sedentary individuals were pseudo-randomly assigned to a physical intervention group (IG: 3 × per week aerobic exercise) or a control group (CG: no regular aerobic exercise). Prior to inclusion in the study, all participants underwent a medical healthcare check involving a short anamnestic questionnaire, auscultation of the lung and heart, and a 12-channel resting electro cardiogram to exclude major physical health risks for subsequent exercise tests and trainings. Subsequently, all participants (IC and CG) performed a graded exercise test (GXT) on a treadmill to determine their individual fitness level. During the study, participants completed this test four times in total: at baseline , after 2 months (T2), 4 months (T4) and 6 months (T6). Parallel to the GXT, participants underwent additional examinations every 2nd months including: MRI (3T and 7T), neuropsychological tests, and blood sampling for epigenetics which are not the focus of the current study. The current work is a purely cognitive and affective behavioral sub-analysis of the data derived from RUNSTUD, focusing on pain perception/pain tolerance, mood and BI, and their interaction dependent on long-term exercise or continued sedentary behavior. The body image questionnaire was acquired exclusively at baseline and at the end of the study , hence, restricting the analyses to these two time-points. The study design is shown in n = 26 . Participants were without any prior history of neurological or psychiatric illness, orthopedic or general health problems that may have prohibited physical activity. From a set of questionnaires . 59 participants with a sedentary lifestyle were initially included in the study, 27 of whom dropped out due to loss of interest and lack of time during the course of the study. Of the remaining 32 participants, complete datasets for this study design were collected only in nventory ; German nventory ) descripnventory , the Stanventory  and the nventory . One of 2max) and maximum heart rate (HRmax). Exhaustion was considered with the attainment of at least two of the following criteria: high levels of blood lactate ; a perceived rate of exertion of ≥ 18 and/or a heart rate (HR) of ±10 bpm of age-predicted maximum (220-age) [2  and HR  were averaged over the last 30 s of each step, and capillary blood lactate samples were taken from the fingertip in the last 15 s of each step. To determine blood lactate concentration, 20 µL of capillary blood were immediately mixed with 1 mL hemolysis solution and analysed via an amperometric-enzymatically procedure . At the same time-points, rating of perceived exertion (RPE) was assessed using the 6  to 20  points Borg scale [All participants performed a GXT on a treadmill  with an initial running speed of 6 km/h, 1% incline and 1∙km/h increments every 3 min to determine maximum oxygen uptake (VO220-age) . VO2  were performed on average. An activity tracker was used to monitor participants’ heart rate, steps and distance of each home training as well as general daily physical activities.max and three to five minutes active recovery with six to eight repetitions. To ensure a steady progression of physical adaptations, exercise intensity was adapted individually according to the results of each GXT (2 and 4 months after baseline). Lactate thresholds were determined using the modified method of [max). Participants in the control group were instructed to maintain their usual lifestyle, to refrain from any kind of exercise and to continue their normal dietary and physical activity practices throughout the study. Both groups (IG and CG) were asked to wear a fitness tracker and to record every physical activity with the tracker.The endurance exercise of the running intervention group was designed as extensive interval training with three to five minutes intervals at 75–80% of HRethod of  (Dmax). The Frankfurt Body Concept Scales   is a selAll items were rated by a 6-point-Likert-scale ranging from ‘very much’ to ‘not at all’. The higher the score the more positive the body image can be interpreted.The Positive and Negative Affect Schedule is one of the most widely used self-report questionnaires for affective measures . It cons2 contact thermode was placed at the non-dominant left volar forearm 2 cm below the arm bend. For the WPT, participants were instructed to press a button with their right hand as soon as experiencing a ‘temperature change’. For the HPT, they were instructed to press a button when the thermal heat perception was accompanied for the first time by a ‘painful sensation’. Three test trials were followed by 5 main trials [Measurements of warmth perception thresholds (WPT) and thermal heat pain thresholds (HPT) were performed pre and post intervention using a MEDOC-TSA II thermal pain stimulation device . Starting at a temperature of 32 °C, the ‘ascending methods of limits’ option with a temperature increase of 0.5 °C per second was used. Therefore, a 9 cmn trials . The tesTo determine pain tolerance (PTol) as a measure of EIH pre and post intervention, participants were asked to place their left hand in 2 °C cold water using a commercially available refrigerated circulating bath . The instructions for the cold pressor test (CPT) were to withdraw the hand from the cold water as soon as perceived pain was no longer tolerable. The elapsed time was measured. For safety reasons the maximal time of testing was set at 4 min. During the test, participants were requested to indicate perceived pain on a VAS (pain intensity) every 20 s. Withdrawal was expected to occur at a maximum pain intensity level on the VAS, thus, validating the PTol measurements. PTol was always determined directly after WPT and HPT.p ≤ 0.05. Additionally, correlation coefficient ‘r’ as an effect size will be reported, with r < 0.30 representing a small effect, 0.3 < r < 0.5 a medium effect, and r > 0.5 a large effect.All statistical analyses were performed using SPSS 25 . Normal distribution was verified by a Shapiro–Wilk test. Differences were considered significant at t-test  or a Wilcoxon rank-sum test .Significant differences between T0 and T6 of the physiological data, the data of the questionnaires , and the data of the pain measurements were statistically analyzed using either a paired t-test or a Mann–Whitney U test.To test for group differences, individual ‘T6–T0’ deltas (Δ) were created for all acquired data and entered in either an independent max in the GXT), mood (PANAS), anxiety (STAI), or pain perception , additional one-tailed correlation analyses were performed using the deltas of T6 minus T0.To investigate whether the dimensions of the FKKS (that show a significant effect due to the intervention) correlate with individual fitness level . Analysis revealed a significant increase in VO2max in the IG from 39.3 ± 5.3 (mean ± standard deviation) to 43.1 ± 6.4 mL/min/kg . The CG showed a significant decrease in VO2max from 41.7 ± 7.5 to 40.3 ± 7.4 mL/min/kg    . Comparing the two groups with each other (IG versus CG) revealed a significant difference between the groups for all three parameters: VO2max , speed at Dmax  and peak running speed   a. Analys= −0.88) b and pea= −0.91) c. The CG= −0.75) .p = 0.001, r = 0.73), while the CG did not reveal any changes in this dimension  = −0.11; p = 0.913, r = 0.04)   of the FKKS only revealed a significant change in the dimension ‘physical efficacy’ (SKEF). The IG showed a significant increase in SKEF from 37.3 ± 6.2 to 44.6 ± 7.1 (t(15) = −4.12,  = 0.04) a. Compar = 0.53) a.p = 0.585, r = 0.14; CG: t(9) = −0.53, p = 0.611, r = 0.17) and ‘self-acceptance of one’s body’  did not reveal any significant changes in any of the two groups or between groups (SGKB: t(24) = 0.05, p = 0.962, r = 0.01; SSAK: U = 52.0, z = −1.50, p = 0.133, r = −0.29)  = −0.56, = −0.29) b,c.p = 0.385, r = 0.23) and no change in the CG  = −0.07, p = 0.946, r = 0.02)  = −0.33, p = 0.752, r = 0.11)   = −0.01, p = 0.991, r = 0.00 ; STAI state: z = −0.77; p = 0.442; r = −0.15)  = −0.90,  = 0.02) a. The PA = 0.11) b. The ac= −0.49) c. Howeve= −0.15) .p = 0.412, r = 0.22; HPT: 1.3 ± 3.2 °C, t(15) = −1.33, p = 0.203, r = 0.32) and the CG  = −1.45, p = 0.187, r = 0.46; HPT: 1.0 ± 1.5 °C, t(8) = −1.98, p = 0083, r = 0.57)  = −0.85,  = 0.57) a,b. Howen = 20 participants , therefore, the statistical analysis for the between group comparison of PTol does lack statistical power and robustness. However, to provide a complete picture of the data, we will still describe the results. While there was an increase in PTol in the IG from 60.2 ± 48.9 to 78.6 ± 88.4 s , the CG group showed a decrease in PTol from 81.5 ± 53.1 to 71.0 ± 47.5 s . However, there was no significant difference between groups  . Unfortunately, the final group size for pain tolerance included only = −0.24) c.max, ΔPANAS, ΔSTAI trait, ΔWPT, ΔHPT and ΔPTol. Analyses revealed a significant correlation in the IG between the ΔSKEF and ΔPANAS Positive Affect Scale  and between the ΔSKEF and ΔHPT   . Howevermax , ΔSKEF and ΔPANAS Positive Affect Scale  and the ΔSKEF and ΔHPT   revealed a significant correlation between the ΔSKEF and Δspeed at D n = 25) .This randomized six months AE-intervention in young healthy sedentary individuals sheds new light on the BI changes occurring in the context of long-term exercise and associated fitness adaptations: For the first time, we demonstrate AE-induced (sub-category) BI-changes and their link to well-established psychophysical phenomena seen after long-term exercise.2max, running speed at Dmax, and peak running speed, hence, providing proof of the efficacy of the PE intervention. While mood scales, anxiety scales and pain indices  revealed no significant change over time in the intervention group, the FKKS revealed a significant sub-category BI-change in the dimension SKEF, supporting previous cross-sectional data related to exercise (see discussion below). The observed changes in the SKEF hint towards AE-induced improvements in ‘physical efficacy’, i.e., sensed and experienced bodily strength, skillfulness, looseness, and flexibility [Regular PE in the intervention group (but not in the control group) was associated with expected fitness increases; these were evidenced by significant improvements in VOxibility , rather Our findings nicely align with previous observations indicating regular AE to have long-term modulatory effects on both, pain and mood: Antinociceptive effects are increasingly acknowledged as long-term effects of regular AE training, with meta-analytical analyses reporting pain threshold elevations , as in oRegarding mood, it has been reported that people undergoing regular AE training have higher levels of mental well-being ,55 and lSelf-efficacy is known to influence different health behaviors  and it wAlthough our findings were centered on exercise-induced changes in ‘physical efficacy’, corroborating previous findings in chronic pain patients  we have Finally, we would like to point out that our findings certainly do not imply that the observed changes in BI are the exclusive variables influencing pain and mood percepts in AE. Rather, we would like to suggest that neurohumoral changes in the brain induced by AE play an elementary role for shaping perceptual and affective aspects of the BI and the resulting neuropsychological state.As discussed above, the association between the change in SKEF and both, the increase in PANAS Positive Affect Scale and the increase in HPT, suggests SKEF to have impact on both behavioral categories. However, a causal relation cannot be derived at the current stage and further empirical research would be needed to prove such a hypothesis. The sample size per group is quite small and future studies are needed to investigate bigger sample sizes. Moreover, due to the small sample size we were not able to investigate gender differences.The FKKS revealed a significant improvement in the IG in the dimension ‘physical efficacy’, supporting the role of BI changes induced by AE. A significant change in mood, anxiety or pain perception could not be detected in either of the groups. However, exercise-induced changes in BI sub-category ‘physical efficacy’ relate to elevated HPT and increased positive mood. This indicates that higher ‘physical efficacy’ induced by AE is associated with elevated mood and higher heat pain thresholds. While it appears to be generally established in the literature that AE has a positive effect on BI, the interrelationships with mood and pain perception studied here are novel and so far not covered by any research we are aware of. Current data from a randomized exercise intervention in healthy participants thus extend the knowledge on changes in BI sub-categories induced by AE and, notably, its relation to pain perception and mood.