One hundred and thirty-six patients presenting for musculoskeletal specialty care completed measures of incapability, pain intensity, adverse childhood experiences, DLEs in the last year, unhelpful thoughts, symptoms of anxiety and depression, and sociodemographic factors. Factors associated with the magnitude of incapability and pain intensity were sought in multivariable analysis. Accounting for potential confounders, greater incapability was associated with greater unhelpful thoughts , but not with stressful life events (either during childhood or more recently). Greater pain intensity was associated with greater unhelpful thoughts and being divorced or widowed , but again, not with stressful life events. The strong association of unhelpful thoughts with magnitude of incapability and pain intensity can motivate musculoskeletal specialists to anticipate patients expressing negative pain thoughts and behaviors. Future studies might account for social and environmental context behind stressful life events and the influence of resiliency and pain-coping strategies on these interactions.Prior studies show that stressful life events are associated with greater magnitude of incapability and symptom intensity. We sought to understand the association of such events (i.e., both adverse childhood experiences Level III, prognostic study On one hand, experiencing ACEs may perpetuate further stressful experiences extending into adulthood, while on the other, such events can serve to catalyze the development of resilience and effective coping strategies that may benefit long-term biopsychosocial health. Either way, mental and social health support may buffer and bolster the experience of adverse events.Recent difficult life events (DLEs) can be a source of ongoing feelings of worry and despair and are associated with greater incapability.17 We sought to understand the interplay of the impact of stressful life events (both ACEs and recent DLEs) alongside feelings of negative mood and negative pain thoughts, on the magnitude of incapability and pain intensity (measured using patient-reported outcome measures [PROMs]) in a musculoskeletal population.There is also an expanding body of evidence for the dominant association between feelings of worry or despair and unhelpful thoughts on the magnitude of incapability and symptom intensity.This study assesses two questions: (1) What are the associations of magnitude of incapability with stressful adverse childhood experiences, a difficult life event in the last year, symptoms of anxiety or depression, and unhelpful thoughts in people with musculoskeletal conditions? (2) What are the associations of pain intensity with stressful adverse childhood experiences, a difficult life event in the last year, symptoms of anxiety or depression, and unhelpful thoughts in people with musculoskeletal conditions? The findings may help prioritize and select mental and social health opportunities in relation to stressful life experiences and psychosocial factors.In an Institutional Review Board (IRB)-approved, cross-sectional study, patients with musculoskeletal illness who presented to one of several musculoskeletal specialist outpatient offices in an urban area of the United States were invited to participate by a research assistant who was not directly involved in their care. All musculoskeletal injuries were eligible for this study. All patients were English- or Spanish-speaking. Participants were excluded if they were younger than 18 years old or had cognitive dysfunction. Patients were asked to complete the survey before or after the visit with the specialist in a private examination room. All patients gave verbal consent before collection of any data. Survey completion by patients was accepted by the IRB as equivalent to written informed consent. All surveys were completed on a tablet using Health Insurance and Portability Accounting Act-compliant software platform . Participants completed surveys measuring the magnitude of incapability, pain intensity, ACEs, DLEs in the last year, negative pain thoughts, and sociodemographic factors .A total of 203 eligible participants started the surveys with 136 (67%) completing them fully. Participants with incomplete survey responses were excluded. Incomplete surveys were due to two main reasons: First, due to the COVID-19 pandemic and minimizing the risk of transmission, patients were invited to complete surveys using their phones rather than office-based tablet devices. The opportunity to complete surveys in their own time rather than in clinic where the tablet would have to be returned, increased the risk of people leaving the office and only partially completing the survey if at all. Second, a temporary malfunction in REDCap during the study led to the survey being automatically shut down before completion. During the study, we introduced the use of tablet devices and a decontamination protocol between patients and the malfunction was rectified. We continued to enroll patients until we had a sufficient number of complete survey responses.One hundred and thirty-six patients with completed surveys were used for analysis. Forty-nine percent (n  =  67) were men. The mean age was 56 years  ±  16 years and 36% (n  =  49) had an annual household income of greater than $121,000 .19 PROMIS CATs are adaptive questionnaires designed to assess a range of health domains with new questions administered based on the participant's last response. PROMIS questionnaires are scaled to the general population living in the United States of America. A score of 50 represents the average score in this population, with one SD being represented by 10 points above or below 50. Lower PROMIS PF scores indicate greater incapability.We measured magnitude of incapability using the Patient Reported Outcome Measurement Information System Physical Function Computerized Adaptive Test (PROMIS PF CAT).21 The NPTQ4 measures unhelpful thoughts in response to nociception using 4 items, each scored on a 6-point Likert scale. Higher PROMIS Anxiety and PROMIS Depression scores respectively indicate greater symptoms of anxiety and depression. Higher NPTQ4 scores indicate greater unhelpful thoughts.We measured mental health using PROMIS anxiety CAT to measure symptoms of anxiety, PROMIS depression CAT to measure symptoms of depression, and a 4-question negative pain thoughts questionnaire (NPTQ4) to quantify unhelpful thinking.Pain intensity was measured using a Numeric Rating Scale for Pain, an 11-point ordinal scale from 0 representing no pain to 10, the worst pain imaginable. Scores vary from 0 to 10 with higher scores representing more adverse childhood experiences. The median (IQR) number of DLEs was 4.5 (IQR  =  2 to 8) and for ACEs 1.0 (IQR  =  0–2.5) (P < 0.001).We measured adverse childhood experiences (ACE) using the ACE scale, which is a validated 10-item binary questionnaire (answered with “yes” or “no”) measuring domains of physical, emotional, and sexual abuse before the age of 18.  0–2.5) . More AC We also used the Holmes–Rahe stress inventory weighted score, where every included life event is given a specific weighting to account for the relative impact it may have on a person. Higher scores represent more impact of DLEs.Finally, we used a list of DLEs based on the Holmes–Rahe stress inventory to count DLEs within the past year: death of spouse, marital separation, divorce, detention in jail or other institution, death of a close family member, major personal injury or illness, being fired at work, major decrease in the health or behavior of a family member, eviction or major damage to one's home, and being a victim of a crime.We obtained local institutional review board approval for this cross-sectional study (Registration No STUDY00001581).t-test and one-way analysis of variance (ANOVA) were used for continuous data with a normal distribution, and Mann–Whitney U tests and Kruskal–Wallis H tests were used for nonparametric continuous data. The Spearman correlation coefficient was calculated to assess the correlation between all continuous explanatory variables and (a) PROMIS PF CAT and (b) NRS pain intensity score. All variables with a P value below .10 in bivariate analysis were moved to multivariable analysis to limit the number of explanatory variables in order to have at least 10 observations per included variable , continuous nonparametric data were described as median with interquartile range (IQR), and categorical data was described in numbers with percentage. Student variable .27 Two The model with NPTQ-4 had the best fit and was selected, and other mental health variables were excluded. ACEs were not moved to multivariable analysis since the P value was above the .10 threshold in bivariate analysis.Due to multicollinearity (intercorrelation) between the mental health variables (Appendix 1), we decided to run multiple models with one mental health variable at the time and to only include the model that had the best model fit (lowest Akaike Information Criterion).An a priori sample size calculation determined that 136 patients would generate 80% statistical power based on a multivariable linear regression model with 8 explanatory variables, if DLEs account for 10% of the variation in PROMIS PF, and if the full model accounts for 25% of the overall variation, with alpha set at 0.05.Statistical analyses were performed in STATA .Question 1: What are the associations of magnitude of incapability with stressful adverse childhood experiences, a difficult life event in the last year, symptoms of anxiety or depression, and unhelpful thoughts in people with musculoskeletal conditions?P  ≤  .001), but not with a higher Holmes–Rahe score  and a divorced or widowed marital status , but not with the Holmes–Rahe score  with psychosocial determinants of health in musculoskeletal populations, including stressful life events such as ACEs and DLEs. Third, 33% of all patients who started the survey did not complete questionnaires and were thus excluded from the study. Although one reason was the technical malfunction on REDCap, which could not be anticipated, future studies might achieve improved completion rates by encouraging patients to complete surveys while in clinic, incentivizing patients, and providing them the option of survey administration via email, telephone call, or text. Fourth, we did not register diagnoses. All patients with any type of musculoskeletal illness were eligible for this study. The distribution of the diagnoses should be representative of musculoskeletal specialty care. Finally, we did not have data on whether the patient completed their surveys before or after the clinician visit, however, our studies have found that one visit does not typical alter questionnaire scores.There were several limitations to this study. First, our study focuses on the interplay between stressful life events and PROMs in a population with musculoskeletal illness ie, people who felt their symptomatic concerns were sufficient to seek musculoskeletal specialty care. We recognize that our findings might differ if the study was conducted in a general population. Second, the number of adverse childhood experiences was limited in our cohort that was relatively economically advantaged . It is possible that there would be a higher occurrence of ACEs in a less privileged cohort, which might alter the results. Studies involving different populations, may spotlight variations in worry, despair, and unhelpful thoughts among different racial and ethnic groups as well as their thoughts and behaviors regarding stressful life events. For instance, American Indians are documented to experience more DLEs and distress, which were associated with greater pain-related symptoms of anxiety and unhelpful thinking (pain catastrophizing).34 This may explain why there was some level of association between recent DLEs, rather than ACEs, and magnitude of incapability . Adults experiencing the effects of DLEs, including symptoms of posttraumatic stress disorder , are shown to report higher levels of pain intensity, pain bothersomeness, greater limitations, and worse mental health .42Unhelpful thoughts may be more important than the recollection of stressful life events (ACEs and DLEs) in the association with one's level of incapability. Perhaps the recollection of stressful life events (which may be easier when events are more recent) is only impactful to the extent that it reinforces unhelpful thinking—a factor that is strongly associated with the magnitude of incapability. ACEs are known risk factors for developing emotional concerns , negative addictive health behaviors , and worse impairment, cognitive function, and chronic conditions across the lifespan into adulthood.44 Such sequelae may occur within the backdrop of a variety of contextual  factors ranging from parental loss or divorce, childhood accidental trauma or nonaccidental trauma, financial hardships, hospitalizations and surgery, and social unmet needs .45In our study, ACEs were not associated with the magnitude of incapability. Another study also shows that ACEs do not correlate with the magnitude of incapability in adults with musculoskeletal illness, unless such events are accompanied by greater symptoms of anxiety or less effective coping strategies.46 Cumulative lifetime adversity (experienced at a moderate level rather than no adversity or nonextreme high adversity) is associated with resilient responses to controlled stressors and is considered beneficial for achieving optimal well-being. Newer measures capturing the cumulative effect of a range of stressful events  may better account for the variation in resiliency over time. A study by Tiet et al., shows youth with higher levels of adverse events were able to express greater resilience if they had a higher IQ, better family functioning, closer parental supervision and monitoring, greater numbers of adults in the household, and higher educational aspirations. Preferred social factors such as an extended network of family and friends complementing one's parental support may increase the likelihood of developing resilience and stimulating a sense of direction and hope. Future studies could better account for such contextual factors within analyses and assess the mediating/moderating effects of resiliency between stressful life events or unhelpful thoughts with level of incapability. Greater control, agency, and confidence in managing one's health may have substantial impact on the extent to which stressful life events associated with level of incapability.Notably, stressful life events in general may stimulate growth, adaptation, and building resilience in the face of adversity. This aligns with our results showing that the unhelpful thoughts have the strongest association with pain experience, regardless of the recent event. As detailed above, future studies might assess the impact of resiliency on the relationship between ACEs, DLEs, and pain intensity as well as opening lines of inquiry that account for different contextual factors, such as social unmet needs, in the relationship between stressful life events and pain experiences in patients seeking musculoskeletal care.Increased pain intensity was associated more with unhelpful thoughts than either DLEs or ACEs, suggesting ameliorating unhelpful thinking is an important factor in accommodating pain. A recent study found that in patients with PTSD-like symptoms (such as intrusive thoughts and distress) following a stressful life event, pain experience was independent of sustained trauma.50 Several authors have expressed exposure to stressful life events during youth may impair endogenous pain inhibition and heighten central sensitization thereby increasing future pain sensitivity and risk of experiencing painful events.51 Research to elucidate these biological mechanisms could continue in parallel with studies designed to uncover the psychosocial factors that may be driving the multifactorial relationships between stressful life events and symptom intensity.52A body of evidence also suggests that ACEs may be associated with seeking care for persistent pain and the activation of physiological  pathways.The finding of an association between unhelpful thoughts and magnitude of incapability and pain intensity among people in musculoskeletal specialty care, but not stressful life events, suggests that unhelpful thoughts are the key factor. There is some evidence that other aspects of mental health  and social health  might act as mediators or moderators of the association between patient-reported outcomes with unhelpful thoughts. Strategies that help focus our attention toward nurturing the healthiest possible thoughts and behaviors regarding symptoms may ameliorate the impact of stressful life events to achieve improved incapability and response to pain.


Both symptoms were reported more frequently in females . When sexes were compared, females reached higher scores in both IGA-CHE and HECSI. Itch and pain intensity correlated positively with disease severity. The intensity of itch and pain significantly influences HE patients’ QoL. A positive correlation between the 6-ISS score and the intensity of itch in the ‘last 3 days’ period was revealed . Conclusions: Itch and pain are common symptoms in HE patients, significantly contributing to the feeling of stigmatization. Providing characteristics of itch and pain may improve HE management. Symptom-decreasing treatment would definitely have a positive influence on patients’ well-being.Background: Hand eczema (HE) is a frequent chronic inflammatory dermatosis. Itch and pain are considered two of the most common and burdensome symptoms of the disease. Yet, the data related to these symptoms are still limited. The aim of this study was to evaluate characteristics of itch and pain in adults suffering from HE. Methods: The study group comprised 100 adult HE patients. An original questionnaire designed by the authors was used to survey the patients. It included questions regarding demographic characteristics such as the duration of the disease, exacerbation count, past diagnostics and treatment, as well as atopic predispositions. Additionally, the itch and pain intensity  during ‘3 days prior to the study’ and the ‘entire disease’ period was implemented. The clinical assessment of the disease severity was performed according to two specific measurement instruments: Investigator Global Assessment for Chronic Hand Eczema (IGA-CHE) scale and Hand Eczema Severity Index (HECSI). To assess patient quality of life (QoL), the DLQI tool was used and to determine the level of stigmatization and for its impact on patients’ life the 6-Item Stigmatization Scale (6-ISS) was employed. Results: Within the period of 3 days prior to the examination, itch was reported by 81.0% of patients ( Hand eczema (HE) is a recurrent inflammatory dermatosis with a high 1-year prevalence reaching 9.7% ,3,4,5. TThe most common primary lesions observed in HE patients are erythema, papules, oedema, vesicles or crusting. Additionally, signs of lichenification, areas of hyperkeratosis, scaling, fissures or erosions may appear. Manifestations of HE usually evolve in severity and clinical presentation over time. ,14 SignsItch can be defined as an unpleasant sensation which leads to scratching. It can be classified as acute or chronic, depending on time criteria  ,18. FourPain itself may be classified in various ways; for example, acute and chronic. The latter is described to affect over 30% of people worldwide . AnotherAssessment of QoL and health-related QoL (HRQoL) has become one of the most important means used to evaluate the effects of interventions in various studies or the impact of the disease on patients’ well-being. The following types of HRQoL instruments can be distinguished: generic instruments—whose results may be compared across different disorders—such as EQ-5D, and disease-specific instruments—assessing the influence of a particular disease on QoL—namely the Quality of Life in Hand Eczema Questionnaire (QOLHEQ). Additionally, a skin-specific group is recognized, as represented by Dermatology Life Quality Index (DLQI) or Skindex-17 questionnaires . CurrentThe aim of this study was to evaluate the prevalence and characteristics of itch and pain in a group of patients suffering from HE. A cross-sectional, prospective study was conducted on a group of 100 consecutive patients from an inpatient  and outpatient clinic at the Department of Dermatology, Venereology and Allergology in Wroclaw, Poland, between 1 February 2022 and 31 January 2023. All patients were recruited by the authors of this research. The whole studied population was diagnosed with chronic HE, based on the clinical picture and time criteria. Inclusion criteria comprised adult age (≥18 years old) and a course of disease persisting for over 3 months, enabling a chronic form of HE diagnosis. All patients with skin lesions that resembled CHE without a definite diagnosis or those waiting for the result of the biopsy were excluded from the study. An original survey, in the form of an investigation sheet, concerning group characteristics was prepared by the authors of the research prior to the study. The survey comprised questions regarding data related to the demographic data, the duration of the disease, exacerbation count, past diagnostics and treatment and atopic predispositions. Additionally, particular clinical features of the itch were investigated such as affected area . Patients were also asked to report where the skin lesions were located  and to declare whether they smoked tobacco or not . Patients completed questionnaires concerning itch and pain assessment, as well as validated Polish versions of the instruments assessing quality of life  and stigmatization level .The study was approved by the local ethics committee (consent no. KB-234/2023) and written informed consent was obtained from all studied individuals. The clinical assessment of the severity of the disease was performed according to English versions of two specific measurement instruments: Investigator Global Assessment for Chronic Hand Eczema (IGA-CHE) scale and Hand Eczema Severity Index (HECSI). All investigators were instructed and trained on their use prior to the study. IGA-CHE  distinguishes 5 categories of HE severity: ‘clear’, ‘almost clear’, ‘mild’, ‘moderate’ and ‘severe’ . The HECSI is a tool employed to assess disease severity, combining the intensity, extent and clinical signs of HE. According to HECSI, both hands of the patient are divided into five areas: fingertips, fingers (except the fingertips), the palm of the hand, back of the hand and wrists. Within each area, the intensity of the following six clinical signs—erythema, induration/papulation vesicles, fissuring, scaling, and oedema—are graded on a scale as follows: 0 (no skin changes), 1 (mild disease), 2 (moderate disease), and 3 (severe disease). For each specific location, the total affected area (considering both hands) is given a score from 0 to 4 for the extent of clinical symptoms . Finally, the score given for the extent of clinical symptoms at each location is multiplied by the total sum of the intensity of each clinical feature and summated. The HECSI score ranges from 0 to 360 points (the maximum severity score) . The folItch and pain intensity were evaluated using a numerical rating scale (NRS). All study participants were asked to assess the severity of the worst itch and pain during the last 3 days as well as the worst itch and pain during the entire period of the disease. The NRS is a unidimensional, brief symptom intensity measurement scale ranging from 0 (no itch/pain) to 10 (worst imaginable itch/pain). The scores of the itch NRS range from no (0 points), mild (1–3 points), moderate (4–6 points), severe (7–8 points), to very severe (≥9 points) . In ordeThe validated Polish version of the DLQI questionnaire was implemented to assess issues related to quality of life . DLQI isThe 6-ISS  ,37 was ut test or Mann–Whitney U test for parametric and non-parametric data, respectively. Depending on the normality, Spearman’s and Pearson’s correlations were used for the correlation assessments. For the qualitative data, the Chi2 test was used. Differences in analyzed data between more than two groups were evaluated, depending on normality, with ANOVA or the Kruskal–Wallis 1-way analysis of variance in ranks. A 2-sided p value of ≤ 0.05 was statistically significant.The statistical analysis of the acquired data was performed using IBM SPSS Statistics v. 26  software. Firstly, all the data were assessed for parametric or non-parametric distribution using the Kolmogorov–Smirnov normality test. The minimum, maximum, mean, standard deviations and ranges were calculated. Based on the normality, analyzed quantitative variables were evaluated using the students n = 47; 78.3%) compared to males . The difference was statistically significant (p = 0.048). Importantly, 28.0% of the studied group (n = 28) was treated systemically with glucocorticosteroids, methotrexate or alitretinoin. Atopic predispositions in the past  were indicated by 45 patients (45.0%). Moreover, 16 females (26.7%) and 12 (30.0%) males showed a correlation between occupation and disease occurrence. Only 27.0% (n = 27) of our patients were previously diagnosed with the use of patch tests (prior to the first visit at our department) and in 14.0% (n = 14) of all cases an allergic contact background was detected. Out of the whole population included in the research, 15.0% of the participants were active smokers. The difference between males and females was statistically significant (p = 0.022)—25.0% of males (n = 10), and 8.3% of females (n = 5) admitted to smoking. Additionally, the difference in the mean number of smoked cigarettes was statistically significant . All data concerning group characteristics are presented in The study group consisted of 60 women (60.0%) and 40 men (40.0%), with an age range of 18–80 (mean 46.0 ± 17.23) years. The mean disease duration time was assessed at 42.5 months (SD = 60.84) and ranged from 3 to 396 months. The total exacerbation count at 12 months prior to the study reached 4.7 ± 3.6. Out of 100 participants, 71 (71.0%) were reported to have been treated because of HE in the past, with a predominance of females (n = 15) belonged to IGA-CHE group 1, 25.0% (n = 25) belonged to IGA-CHE group 2, 37.0% (n = 37) belonged to IGA-CHE group 3, and 23.0% (n = 23) belonged to IGA-CHE group 4. Regarding the HECSI, the mean value was equal to 35.0 ± 27.8 points, with 29.3 ± 26.7 points for males and 38.8 ± 28.1 points for females. n = 11; 27.5% in both groups), whereas women predominated in IGA group 3 . No correlation between active smoking or the number of smoked cigarettes and disease severity was found.Considering the IGA-CHE, no patients were allocated in IGA-CHE group 0. Briefly, 15% of individuals (n = 81), of individuals reported itching, whereas 53.0% (n = 53) of patients experienced pain during the same period of time. During the ‘last 3 day’ period both symptoms were reported more frequently in females  vs. 28 males (70%), p = 0.022; pain: 47 females (78.3%) vs. 16 males (40.0%), p = 0.033). During the whole disease period, 100% of the studied group reported itching, including both males and females. In the same period, pain was perceived by 53 females (88.3%) and 29 males (72.5%). For the whole studied population itch intensity was assessed to be 6.4 ± 2.7 points, for the entire disease period, which corresponds to ‘moderate’ itch, and for the ‘last 3 days’ period, it was assessed to be 3.9 ± 2.9 points, representing ‘mild’ itch (both measured with NRS). The pain severity for the entire disease and the ‘last 3 days’ period was rated as 4.6 ± 3.2 points and 2.6 ± 3.1 points (both corresponding to ‘mild’ pain), respectively. Evaluating outcomes with regard to the cut-off values, analyzing the entire disease period, the ‘very severe’ itch group was significantly more often represented by females in comparison to males (22 (36.7%) females vs. 5 (12.5%) males; p = 0.008), while in the ‘moderate’ itch group the predominance of males was observed (21 (52.5%) males vs. 19 (31.7%) females; p = 0.037). The results of the itch and pain assessment are included in Within 3 days prior to the examination, the majority, 81.0%  . Moreover, comparing the particular IGA-CHE severity groups, statistically significant differences in itch (p = 0.029) and pain (p = 0.002) intensity were found, only for the ‘last 3 days’ period. Results of the HESCI score also correlated with itch severity, in the entire disease period . No such correlation was found for the ‘last 3 days’ period. In the analysis of pain severity, a correlation with HECSI was found for both the ‘last 3 days’ and the entire disease period . No correlation between active smoking or the number of smoked cigarettes and itch or pain severity was found.A positive correlation between itch as well as pain intensity and IGA-CHE was observed, when these parameters 3 days prior to the examination period were taken into account  . Addition = 65) of cases only hands were affected by eczematous lesions. Out of the whole population, 23.0% of patients reported foot skin involvement (n = 23). The remaining group  declared a disseminated form of the disease. Most of the investigated population  answered that itch was present only within skin lesions, whereas 13.0% of respondents experienced itching additionally in unaffected skin areas. No significant differences between sexes regarding the above-mentioned features were found. In all respondents reporting pain, it was localized only within skin lesions. As for the localization of the lesions, in 65.0% (Severity of both itch and pain correlated with reduced QoL measured with DLQI .p = 0.027). No correlation between the 6-ISS score and the intensity of itching in the ‘entire disease’ period, the intensity of pain in the ‘last 3 days’ period, or the intensity of pain in the ‘entire-disease’ period was found.Based on the level of stigmatization, a positive correlation between the 6-ISS score and the intensity of itching in the ‘last 3 days’ period was recognized . When the entire disease period in the individuals studied in our research was considered, itch correlated positively with disease severity measured with the use of both of the following instruments: IGA-CHE and HESCI. These results are in line with those of Ruppert et al. [HE is described as one of the most frequently occurring diseases in patients suffering from itch . Simultat et al.  in whicht et al. . Itch can be one of the various symptoms in patients with other dermatoses such as HS (acne inversa), psoriasis and atopic dermatitis ,55,56. Cn = 53) of patients reported pain within the last 3 days prior to the study . In their research, Weigandt et al. [Another symptom of HE that is as yet not fully characterized is pain. In a study by Dibenedetti et al. , the pret et al.  determint et al.  conductet et al. . Dependit et al. . Nevertht et al. ,60,61.Quality of life and its improvement are some of the most frequently discussed issues in modern medicine and patient-oriented management. Alongside AD, moderate-to-severe HE is proven to have a stronger impact on QoL compared to most other chronic conditions . A signiOur study has several limitations that should be considered. The extent of the study involved only one center from Wroclaw, Lower Silesia, Poland, which reduces the variability of the population. The small sample size is also worth mentioning. In the future, a multicenter study involving patients from different geographical regions would be of special importance. So far, our group focuses neither on the pathogenesis of itch and pain, nor the pathways responsible for transmitting them, which would be crucial for subsequent investigations. Nevertheless, it should be emphasized that our work extends the current knowledge on subjective symptoms in HE patients.Because of the wide range of etiological factors and clinical pictures, HE remains a disease entity which should constantly be investigated. Being one of the most frequently reported HE complaints, itch influences all aspects of patients’ life. Concerning the data suggesting that up to 81.0% of individuals suffer form HE, itch correlates with disease severity and is often associated with HE exacerbations. Our study shows that itch is reported more frequently by females (88.3% vs. 70.0%), concerning that at the ‘3-days-prior to the study’ period. Its prevalence was higher than the incidence of pain within a comparable period (81.0% vs. 53.0%). Pain in HE is a symptom which requires more attention and is often underestimated. Pain, similarly to itch, dominates among females. Our study demonstrates also that pain intensity correlates positively with the severity of the disease. Both itch and pain are major symptoms associated with HE, impairing patients’ well-being. Developing data characterizing them may help both physicians in improving their management and scientists in creating new therapeutic options. Symptom-decreasing or even liberating treatment would definitely have a positive influence on patients’ QoL and stigmatization level.


Background and purposeGiven that chronic pain has become a major problem in recent years, affecting approximately 30% of the general population, this study used the Japanese version of the Short Form-8 (SF-8) to investigate (1) the quality of life (QOL) of patients with burning mouth syndrome (BMS) or persistent idiopathic facial pain (PIFP) (compared with a Japanese control group) and (2) whether therapeutic intervention improves the QOL and reduces pain (comparison between 0 and 12 weeks) of patients with BMS or PIFP.Materials and methodsA total of 63 patients diagnosed with either BMS (n=45) or PIFP (n=18) were included in this study. The diagnostic criteria for BMS and PIFP were established based on the third edition of the International Classification of Headache Disorders.ResultsOur study results showed that while Physical Component Summary (PCS) in patients with BMS or PIFP improved with treatment, it did not improve to the national standard value (NSV) after 12 weeks of intervention. In contrast, the Mental Component Summary (MCS) improved to the same level as the NSV after 12 weeks of intervention.ConclusionsWe found that therapeutic intervention improves MCS and reduces pain; however, improving PCS requires time. Chronic pain has become a major problem in recent years, affecting approximately 30% of the general population . The majChronic pain in the orofacial region includes various conditions such as burning mouth syndrome (BMS), persistent idiopathic facial pain (PIFP), and nonorganic temporomandibular joint disorder. BMS and PIFP are commonly encountered in daily clinical practice . Since tThe concept of health-related quality of life (HRQOL) has been generally used as a multidimensional assessment of how disease and treatment affect a patient’s sense of overall function and well-being . It is aIn this study, the SF-8 Japanese version  was usedThis article was previously posted to the medRxiv preprint server on May 22, 2023.Ethical guidelinesThis study was conducted as per the principles of the Declaration of Helsinki and was approved by the Ethical Review Committee of Nagoya University Graduate School of Medicine  and the Ethical Review Committee of the School of Dentistry, Aichi Gakuin University (no. 41). All the participants provided written informed consent.Study design and patientsPatients who had a first visit to the liaison outpatient clinic of the Department of Oral and Maxillofacial Surgery, Aichi Gakuin University Dental Hospital, between May 10, 2010, and April 21, 2021, were diagnosed with BMS or PIFP by a dentist using the third edition of the International Classification of Headache Disorders  [A structured clinical interview was conducted to establish a psychiatric diagnosis based on DSM-5. Regarding therapeutic interventions, serotonin noradrenaline reuptake inhibitors (SNRIs) are more commonly used than tricyclic antidepressants because of their fewer adverse effects, although antidepressants have been widely used for the treatment of chronic pain. Our previous study reported that SNRI duloxetine is effective for chronic pain in the orofacial region -17. DuloOutcome measuresAs the main outcome, for patients who received the therapeutic intervention, the SF-8 at the initial visit and after 12 weeks of intervention was evaluated and compared with those of the Japanese control participants. The SF-8 consists of the following items: general health, physical function, daily role function , physical pain, vitality, social function, mental health, and daily role function   50) for each item. Based on the eight items, two summary scores, “Physical Component Summary (PCS)” and “Mental Component Summary (MCS),” were calculated to indicate physical and mental health, respectively. Higher scores indicated higher QOL for both PCS and MCS. A group of healthy participants matched in number with the patient group was also created from the NBS data and used as the NSV.Additionally, pain intensity was evaluated using a visual analog scale (VAS). To evaluate depression in 63 patients with BMS and PIFP, Beck’s depression inventory  was used as a subjective index, and the Hamilton Depression Rating Scale , which uses semi-structured interviews by a trained psychiatrist, was used as a highly precise objective index ,19.The score for each item of the SF-8 was indicated by a deviation score based on the NSV (50). In addition, a summary score was calculated by multiplying the score of each item by the coefficient summary score. Items closely related to the physical summary score were 1-4, and items closely related to the mental summary score were 5-8.Statistical analysisData are expressed as median (IQR) or number. Because the sample size was small and the data did not follow a normal distribution, we adopted the median value instead of the average value. For statistical testing, the Mann-Whitney U test was used to compare the differences between the two independent groups for continuous variables. The two-sided statistical significance level was set at p ≤ 0.05. Statistical analysis of the recorded data was performed using SPSS Statistics version 26 .Table As shown in Figure Statistically significant differences were observed between 0 and 12 weeks, between 0 weeks and NSV, and between 12 weeks and NSV. The SF-8 MCS was 45.4 (38.4-49.6) at 0 weeks and 48.1 (44.4-52.3) at 12 weeks, and the NSV was 49.86 (45.96-53.49). Statistically significant differences were observed between 0 and 12 weeks and between 0 weeks and NSV. However, no statistically significant difference was observed between 12 weeks and the NSV group.Figure The VAS score was 53 (32.5-77) at 0 weeks and 26 (8.5-46) at 12 weeks. The BDI was 12 (6.5-18.5) at 0 weeks and 6 (1.5-10.5) at 12 weeks. The HDRS scores were 6 (3-12) at 0 weeks and 2 (1-3) at 12 weeks. All the parameters showed statistically significant differences between 0 and 12 weeks.This study showed that although PCS in patients with BMS or PIFP improved with treatment, it did not improve to NSV after 12 weeks of intervention, whereas MCS improved to the same level as NSV after 12 weeks of intervention. The results demonstrated that the treatment intervention improved the BDI and HDRS scores, a measure of depression. Emotional factors have been reported to be strongly involved in the deposition and relief of chronic pain and may have diverse effects on pain expression . This stPrevious reports using the SF-8 have included evaluations for rheumatism  and stroMCS recovered, while PCS did not recover to NSV in this study. Thus, emotional turbulence may cause muscle hyperactivity induced by the central nervous system, resulting in parafunctional habits . DepressThis study has several limitations. First, the number of patients and the study duration were limited , and it was a single-center study. Second, it was not possible to properly evaluate the effect of treatment with duloxetine because this study was not an intervention study such as a randomized controlled trial. In addition, as the SF-8 is a scale that can be used for a wide range of patients, from normal participants to patients with chronic diseases, it is not disease-specific for chronic pain in the orofacial region.In conclusion, we used the SF-8 Japanese version to investigate (1) the QOL of patients with BMS or PIFP compared with a Japanese control group and (2) whether the therapeutic intervention improves QOL and pain reduction (comparison between 0 and 12 weeks). The results showed that statistically significant differences were observed between the QOL of patients with BMS or PIFP and a Japanese control group. Therapeutic intervention improved MCS and reduced pain; however, the PCS improvement took time.


Previous studies have demonstrated a relationship between headaches and temporomandibular disorders (TMDs). Moreover, recent studies have shown functional, anatomical, and neurological associations between the temporomandibular joint (TMJ) and upper cervical spine. This study aimed to investigate the effectiveness of manual therapy and cervical spine stretching exercises for pain and disability in patients with myofascial TMDs accompanied by headaches.Thirty-four patients recruited from Gyeryong Hospital with headaches and diagnosed with TMDs were randomly assigned to the experimental (n = 17) and control (n = 17) groups. Headache impact was assessed using the Korean Headache Impact Test-6. Masseter myofascial pain was measured using the visual analog scale, and TMJ pressure pain threshold levels were evaluated using an algometer. Neck pain intensity was assessed using the numerical rating scale. Once per week for 10 weeks, the experimental group received cervical spine-focused manual therapy and stretching exercises alongside conservative physical therapy, and the control group received conservative physical therapy alone. Patients were evaluated at baseline and 5 and 10 weeks post-intervention.After the intervention, the experimental group exhibited significant reductions in the cervical kyphotic angle, Korean Headache Impact Assessment score, neck pain intensity, TMJ pain pressure threshold, Neck Disability Index score, and Jaw Functional Limitation Scale level compared with the control group (p < 0.01).Manual therapy and stretching exercises could help resolve TMDs accompanied by headaches through biomechanical changes in the cervical spine. These findings may guide protocols and clinical trials involving manual therapy that align morphological structures. Temporomandibular disorder (TMD) is the second most common musculoskeletal disorder that causes pain and disability . TMDs arRecently, functional, anatomical, and neurophysiological relationships have been reported between the TMJ and upper cervical spine. Associations between the cervical spine, TMDs, and head and neck conditions, such as neck pain (NP) and headaches, are widely recognized . GonçalvThe association between NP and TMD has also been studied extensively . There iMoreover, patients with TMDs exhibit reduced neck flexor and extensor muscle endurance . The autCatanzariti et al.  reportedRegarding the association between the neck, headache, and TMJ, it can be hypothesized that interventions targeting the cervical spine may also affect patients with TMD-related headaches. Therefore, we explored the effects of cervical spine-focused manual therapy on headaches and cervical pain intensities, TMJ pressure pain threshold (PPT), cervical kyphotic angle, Neck Disability Index (NDI), and Jaw Functional Limitation Scale score (JFLS) without administering medications to patients with myofascial TMD accompanied by headaches over a specific period.This study aimed to investigate the effectiveness of manual therapy and cervical spine stretching exercises for pain and disability in patients with myofascial TMD accompanied by headaches.Patients who experienced headaches and were diagnosed with one or more symptoms of TMD  at the Gyeryong Hospital  from July to September 2022 were included in this study. The required sample size was calculated based on Cohen’s sampling formula using the G-power program . The effect size, significance level, and power were set to 0.25, 0.8, and 0.8, respectively. The inclusion and exclusion criteria were based on the study of La Touche et al. .The inclusion criteria were as follows: (1) headaches experienced after the diagnosis of TMD, accompanied by one or more symptoms such as mouth-opening restriction, TMJ pain, and TMJ clicks; (2) a Korean Headache Impact Test-6 (KHIT-6) score of ≥ 50 points indicating the need for medical care ; (3) abiThe exclusion criteria were as follows: (1) the DC/TMD Axis I, Group II: including disc displacement with or without reduction and mouth opening limitation; or Group III: arthralgia, arthritis, and arthrosis ; (2) a hThe study’s purpose and procedures were explained to the participants. Subsequently, only those who provided written consent to participate were included. The patients were evaluated using a pre-prepared questionnaire to determine eligibility. To meet the inclusion criteria, after ruling out dental pain, patients who reported referred pain in response to masticatory muscle palpation were diagnosed as having masticatory myofascial pain. Patients who met the criteria for arthralgia and/or intraarticular TMD were excluded.First, the Headache Impact Assessment Questionnaire was used to select patients with a KHIT-6 score of ≥ 50 points, indicating the need for medical care . The masThe Korean version of the Headache Impact Assessment Questionnaire standardized by Chu et al.  was usedA radiographic imaging device  was used to measure the cervical kyphotic angle. Depending on the patient’s age, sex, and physique, the exposure was administered for 0.02 s at 200 mA, 70–80 kV, and at a distance of approximately 2 m. The images were captured using digital films.The patients’ radiographs were obtained with the Frankfurt plane parallel to the floor and the jaw in the intercuspal position. The average value of the angles measured from the imaging data was used for the analysis Fig. .The cervical kyphotic angle was measured at baseline and 5 and 10 weeks post-intervention based on the Ishihara index (ISHIHAR-I). The category of 5–25% is defined as the normal range; >25% is defined as excessive forward bending; 0–5% is defined as straightening; and < 0% is defined as kyphosis . TakeshiThe NDI is a self-rated evaluation tool used to assess the limitations in daily life due to NP. Individual item scores range from 0 (no disability) to 5 , with a total possible score of 50. Higher total scores indicate a greater severity of neck disorder. Scores of 0–4, 5–14, 15–24, 25–34, and ≥ 35 are classified as no, mild, moderate, severe, and complete disability, respectively. Vernon and Mior [NP intensity was assessed based on the intensity of pain experienced by the participants during the study using the numerical rating scale (NRS). The NRS is a pain measurement tool developed by Sartain and Barry  that preThe Jaw Functional Limitation Scale-20 (JFLS-20) evaluates functional jaw impairment. However, this scale includes sexual questions that do not conform to Korean culture; therefore, its short version, the JFLS-8, was used in this study. The internal consistency of the JFLS-20 is reportedly 0.90, whereas that of the JFLS-8 ranges from 0.84 to 0.86, indicating excellent reliability, sensitivity, and validity . FurtherThe pressure pain threshold was measured using an algometer  to assess TMJ pain levels. The device was pointed toward the skin, overlaying a tender point in the TMJ (masseter muscles). The average score was calculated to obtain a single score.According to Chesterton et al. , when thwww.randomize.org).In total, 42 individuals with myofascial TMD accompanied by headaches were recruited and 34 with minimum scores ≥ 50 points on the KHIT-6 were selected. The pain intensity of the trigger points in the masseter muscle of these patients was > 30 mm on the 100-mm VAS. The 34 selected patients were assigned to two groups with 17 participants each: the experimental group  and the control group . Patients were assigned using a randomized allocation method . Interventions were performed by the same physiotherapist with over 20 years of experience in manual therapy. Patients in both groups were evaluated after 5 and 10 weeks of intervention.Conservative physical therapy was initiated in both groups, and it comprised surface heat treatment, infrared therapy, interference current therapy, and ultrasound treatment, once per week for 10 weeks. The procedure was as follows.The protocols reported by La Touche et al.  and Cali(1) Modified upper and lower cervical flexion mobilization (C0–C4): Patients were asked to lie supine with the cervical spine in a neutral position. The therapist held the occipital bone with the first finger and medial aspect of one hand, while the other hand was placed on the patient’s forehead. The mobilization force was sufficient to bend the upper and lower cervical spines as the hand provided cephalic traction; caudal pressure was applied using the hand on the forehead. This technique promoted flexion of the upper and lower cervical spines (C0–C4), at a slow rate of 2 s per oscillation (0–5 Hz) for a total of 10 min. In a previous study, this cervical flexion mobilization was used for the upper cervical spine . Further(2) Modified central posterior-anterior mobilization (C4–C5) : Patient(3) Craniocervical flexor stabilization exercises: For the craniocervical flexor stabilization exercises, we followed the protocol described by Falla et al. , which f(4) Sustained natural apophyseal glide for headache : The pat(5) Stretching exercises in the cervical region: The upper trapezius, scalene, semispinalis capitis, splenius capitis, and sternocleidomastoid muscles are directly involved in head positioning. Misalignment of the head and neck has been reported when these muscles are shortened due to contraction . StretchSPSS  was used for all statistical analyses. Descriptive statistics (means and standard deviations) and frequency analyses were used to assess the baseline characteristics of patients. The Shapiro–Wilk test was performed to determine data distribution normality in both groups. Repeated-measures analysis of variance, with time  as the within-subject variable, was performed to investigate the effect of cervical spine-focused manual therapy and stretching exercises on pain and disability in patients with myofascial TMD accompanied by headaches. The Bonferroni test was conducted for post-hoc analysis; p < 0.05 was considered statistically significant for all analyses.Baseline characteristics of the patients are presented in Table Findings of the between-group comparison of the changes in pain levels after the interventions are presented in Table A greater reduction was noted in the intensity of headaches, NP, and TMJ pain evaluated after 10 weeks of intervention in the experimental group than in the control group (p < 0.01). Additionally, the headache, NP severity, and TMJ pain levels in the experimental group decreased significantly from their baseline values (p < 0.01) after 5 and 10 weeks of intervention. NP intensity and left TMJ pain showed significant reduction after 10 weeks of intervention compared with those after 5 weeks of intervention (p < 0.01). In the control group, the right TMJ PPT showed a significant decrease after 10 weeks of intervention  after the intervention. Significant between-group interactions were observed in terms of changes in the cervical spine kyphotic angle (ISHIHAR-I), neck disability level (NDI), and JFLS-8 scores (p < 0.01). The level of neck dysfunction improvement was also statistically significant (p < 0.01). Although limited improvements were observed in the control group, conservative physical therapy significantly reduced the PPT, NDI, and JFLS levels after 10 weeks of intervention. This can be understood in the context of a study by Suvinen et al. , who repThe DC/TMD includes a new classification called headache attributed to TMD (HATMD), indicating that myalgia and TMJ arthralgia are related to headaches . The IntThe DC/TMD suggests that headaches originate from a myofascial trigger point, induced during palpation of jaw joint muscles and extensive jaw movement, and not from the intracranial structure , 35. AccIn this study, we also looked into changes in the cervical kyphotic angle to improve the diagnosis of the presumed cause of headache secondary to TMJ dysfunction. The causes of “turtle neck”, “straight neck” and “cervical kyphotic angle” include trauma and muscle tension, neck disc, post-neck facet joint syndrome, long-term neck flexion, and secondary phenomena due to thoracic or lumbar deformation . This poDe Laat et al.  reportedHowever, in a previous study , the autThere were no statistically significant results confirming whether the increase in the cervical kyphotic angle correlated with headache, neck pain, and TMJ pain levels; however, the results showed a significant reduction in headache, neck pain, TMJ pain, cervical dysfunction, and JFLS levels after 10 treatments. Therefore, the PPT levels for the masseter muscles and headaches indicate that morphological changes induced by cervical spine treatment can produce hypoalgesic effects.To the best of our knowledge, no study has demonstrated the activation of descending inhibitory pathways or the occurrence of bilateral hypoalgesic effects in the trigeminal region after applying cervical spine-focused manual therapy and stretching exercises in patients with myofascial TMD accompanied by headaches . HoweverGenerally, manual therapy, including TMJ mobilization and the soft tissue technique , improveThe manual therapy and stretching exercises performed in this study may have improved TMD-related headaches through biomechanical changes in the cervical spine. Alternatively, the patients’ symptoms may have simply improved over time. However, in comparing the duration of the study to the average duration of patient symptoms , it is unlikely that the pain would have significantly improved over time without the intervention.Our study results showed that manual therapy and cervical spine stretching exercises were associated with improvements in the function and pain of patients with TMDs and improvements in the biomechanics of the cervical spine. Pain and disability were successfully alleviated with physical therapy designed for TMD symptoms accompanied by headaches. These study results will improve our understanding of the biomechanical basis of TMDs accompanied by headaches.Nevertheless, this study has some limitations. First, the control group received 40 min less total therapy per week than the experimental group. In future studies, to better evaluate the significance of between-group differences, the control group should receive the same duration of therapy as the experimental group. Second, the therapist and patients were not blinded because of the patients’ control of the medication. Third, changes in the cervical kyphotic angle of the neck bone, headaches, TMD symptoms, and pain significantly improved after therapy, but future studies are needed to determine whether this is a minimal clinical importance difference that can be recognized and valued by patients.The application of manual therapy and cervical spine stretching exercises improved the intensity of headaches, NP, and TMJ pain evaluated after 10 weeks of intervention in the experimental group compared to that in the control group. Additionally, the headache, NP severity, TMJ pain levels, and neck dysfunction in the experimental group decreased significantly from their baseline values after 5 and 10 weeks of intervention. After 10 weeks of intervention, the cervical spine kyphotic angle and neck disability levels decreased significantly more in the experimental group than in the control group. The current findings are significant as they suggest the possibility of pain recovery and improvement of function by achieving structural changes in the cervical spine in patients with TMDs accompanied by headaches. Moreover, these findings may guide protocols and clinical trials involving manual therapy that align morphological structures.


Cancer incidence and mortality are increasing worldwide, and pain is the most common symptom patients experience. Despite developments in cancer pain management and guidelines, the pain often remains undertreated. Effective pain management ultimately involves overcoming several complex institutional, patient, and healthcare provider-related barriers.The objective of the study was to explore and describe healthcare providers’ perceptions of the cancer pain management barriers at a hospital in Zambia.A descriptive qualitative study was conducted. Data were collected from 10 purposively sampled medical doctors and registered nurses using prepiloted semistructured individual interviews. Interviews were audio recorded and transcribed verbatim. Thematic analysis was done, and trustworthiness was enhanced based on the criteria described by Lincoln and Guba. Ethical principles, as outlined in the Declaration of Helsinki, were adhered to.Three themes emerged, namely patient-related barriers , healthcare provider-related barriers (knowledge and perceptions and language barriers), and institution-related barriers (resource limitations and lack of standards and guidelines). Healthcare providers’ views that cultural beliefs about cancer being caused by witchcraft and the use of traditional medicine and services are barriers to cancer pain management were unique to this study.Cancer pain management requires a total pain management approach that addresses the barriers to pain management strategies from a patient, healthcare provider, and institutional perspective. The knowledge deficit among patients and healthcare providers is a barrier to cancer pain management and one of the most common challenges reported in the literature. This study further points toward a need to develop culturally competent healthcare providers. Cancer incidence and mortality are increasing worldwide, with pain being the most common symptom experienced by patients . HoweverCancer incidence and mortality are global concerns. In 2020, 19.3 million patients were newly diagnosed, and 10 million died of cancer . The gloPain is experienced by 55% of patients receiving anticancer treatment, 66% of patients with an advanced, metastatic or terminal disease , and 10%Pain relief is necessary at all stages of cancer , and betThe backbone of cancer pain treatment is pharmacological interventions. However, other therapies should be included in a holistic approach to managing pain, namely radiotherapeutic, anesthetic, neurosurgical, psychological, physical therapy, and spiritual and social interventions . Cancer However, despite developments in cancer pain management and guidelines, the pain often remains undertreated , with upSeveral barriers to effective pain management have been identified. These barriers are context-specific but can be broadly categorized as patient-related, healthcare provider-related and institution-related . PatientIn Zambia, studies by A descriptive qualitative design  exploredThe hospital functions as an outpatient treatment facility that offers radiation therapy, chemotherapy, hormonal treatment and palliative care to patients with cancer. It is a government grant-aided hospital, and at the time of data collection, treatment was free for all Zambians. The hospital serves as a national referral centre for patients with cancer nationwide, with a catchment population of approximately 17 million, covering the ten provinces of Zambia. In addition, the hospital also caters to patients from neighbouring countries, including Malawi, the Democratic Republic of Congo and Zimbabwe. When patients require admission, they are referred to a nearby hospital.The study had one research question: What are the barriers to cancer pain management at a specific hospital in Zambia? The subquestions were: What are the patient-related barriers to cancer pain management? What are the healthcare provider-related barriers to cancer pain management? What are the institution-related barriers to cancer pain management?The population consisted of all healthcare providers working at the hospital, which included 38 registered nurses and 12 medical doctors. Purposive sampling  was usedData were collected from June 2017 to December 2017 using semistructured individual interviews based on an interview schedule. The interview schedule was piloted with three participants, and information from the pilots was not included in the presented data. The semistructured individual interviews were opened with a broad central question. After that, probes were used to focus on the patient, healthcare provider and healthcare institution. The interview questions are included in Data were thematically analysed . First, Spending adequate time with participants and establishing rapport;Providing dense descriptions of the research methodology and the findings;Purposively sampling participants who were knowledgeable about cancer pain management and who were working in the specific setting;Keeping an audit trail;Co-coding and reaching a consensus about the subcategories with an independent coder;Audio-recording interviews and using verbatim transcriptions; andParticipant triangulation, including doctors and nurses.Lincoln and Guba's in  criteriaEthical approval to conduct the study was sought from the Tshwane University of Technology Research Ethics Committee [Ref #: FCRE 2016/04/002 (SCI)(2)] and Eres Converge IRB [Ref #: 2016-Oct-006]. Gatekeeper permission was given by the chief executive officer of the hospital where the research took place. Interviews were conducted during break times or after work to prevent the research from impacting service delivery. Written informed consent was also obtained from each participant before data collection, and participation was voluntary. Confidentiality and anonymity were ensured by anonymising the hospital and using codes for interviews and participants. Electronic data were password protected, and hard copies were securely stored for 5 years and then destroyed.The results focused on the sample's characteristics and perceived barriers to cancer pain management.Ten participants, including seven professional nurses and three medical doctors, participated in the study. Two participants had prior specialized training in oncology; one oncology-specialized medical doctor and one oncology-specialized professional nurse. Participants’ experience as healthcare providers ranged between 2 and 17 years, while years of experience in oncology ranged between 2 and 11 years.Patient-related, healthcare provider-related, and institution-related barriers were identified and discussed. The three themes yielded six categories and 16 subcategories (SC), as outlined in Two patient-related barriers were identified: barriers related to patients’ biographic characteristics and patients’ knowledge and perceptions of cancer pain and pain management.The perceived barriers related to patients’ biographic characteristics included financial constraints, multiple illnesses, the use of multiple medications, and patient beliefs.Some patients would rather use the little money they have on food and daily expenses than use it for transport to come for a refill of pain medication. (Nurse)Participants explained that patients who experienced financial constraints (SC 1) lacked the financial means for transport, resulting in them not honouring their appointments at the hospital and constraining their ability to adhere to treatment. The following statements supported this finding:Patients and their relatives must travel long distances to access the specialized service. (Doctor)Because some patients have many more illnesses apart from cancer, they tend to have many more drugs to take, and it is confusing for them to know which drugs to take and when. (Nurse)Managing multiple medications also led to confusion about the correct use among patients and caregivers. Participants indicated that multiple medications often contributed to nonadherence to prescribed pain medication. Some participants mentioned that having multiple chronic diseases (SC 2) in addition to cancer led to patients taking several types of medication. The following statement reflects this subcategory:Patients who have cancer pain turn to traditional healers. They believe their illness is caused by witchcraft. Hence, they are more comfortable seeing the traditional healer because they think he understands their problem better than the doctors at the hospital. Some patients think only the herbal medications can help in cases where they have severe pain, so they will just be taking home remedies for their cancer pain. (Nurse)Participants further described patients’ beliefs (SC 3) that cancer was caused by witchcraft as a barrier to pain management as patients often consulted traditional healers and preferred using their herbal medication to the prescribed pain medication. Participants were of the view that pain management was consequently compromised. One participant explained:Because of traditions, culture and beliefs most male cancer patients will not tell you they are in pain … pain is not supposed to be announced or publicized … in our culture most male patients will not tell you that they are in pain. (Nurse)When a man complains of pain, it is seen as a sign of weakness. (Nurse)Also, regarding gender (SC 3), it is difficult to obtain an accurate report of pain from male patients as there is a belief that an acknowledgement of pain is a sign of weakness, not befitting men. Participants explained that this notion prevented men from reporting pain, resulting in poorly managed cancer pain. The following quotes reflect this cultural belief:they will formulate their instructions or make up any timings and dosing that suits them because they cannot read. (Nurse)…Healthcare providers explained that patients’ limited health literacy (SC 4) was a barrier to cancer pain management. Participants also stated that patients’ failure to read the instructions on the prescriptions led to incorrect use of prescribed pain medication. Furthermore, limited comprehension of the meaning of specific instructions, usage, storage, and the expiration of the drugs negatively impacted patients’ understanding of healthcare providers’ explanations. In the view of healthcare providers, illiteracy had a bearing on how patients would interpret the cause of pain, how it could be relieved, how analgesics work, and the cancer disease process. Participants explained:Some patients cannot read; they cannot even tell if the drug has expired or not … they will, in fact, even mix the old medicines with the one they have just gotten recently. They cannot distinguish which is a new or expired drug. (Nurse)Most cancer patients think pain is part of the disease, so they will not tell you they are in pain, … they think it is okay to have pain if you have cancer, … Patients think experiencing pain is part of the disease process. (Doctor)Participants explained that patients perceived (SC 5) pain to be acceptable as this was to be expected when diagnosed with cancer. Patients, therefore, felt that it was not necessary to report their pain:Some patients have misconceptions that strong opioids will kill them instead of relieving the pain. (Nurse)…some patients think that taking morphine will cause cancer to become resistant to chemotherapy or radiotherapy. (Nurse)Participants expressed the view that patients attached certain myths to cancer pain management and how the drugs intended to relieve their pain instead caused them harm. Participants explained:Two categories of barriers related to cancer pain management were derived from this theme: competence in the assessment and management of pain, and disbelieving patients’ reports of pain.Some health care providers do not know how to combine certain drugs to maximize the effect of pain relief. (Nurse)Due to limited specialized training, healthcare providers experienced challenges in knowing (SC 6) which drug combinations worked well with various types of pain and how one drug could replace another while maintaining the same and safe desired effect. This finding was expressed as follows:We have the pain assessment forms, but using them confidently is difficult. (Nurse)The way I would manage a headache caused by malaria is different from the way I would manage a headache caused by a brain tumour. (Doctor)Healthcare providers have challenges in deciding what to prescribe to the patient to help relieve the cancer pain … health care providers sometimes unable to confidently decide on how to classify, grade and resolve the patients’ pain. (Nurse)Some participants reported that despite knowing about cancer pain management, they lacked confidence and feared being questioned about their practice:I may be a Zambian but can only fluently speak and understand 2 to 3 languages, worse still is when it comes to translation … Some patients are unable to describe the pain so that it can be graded.” (Nurse)… some local languages do not have the grades to say mild, moderate or severe. (Nurse)Participants also mentioned that Zambia's multiple local and seven officially recognized languages resulted in language barriers (SC 7) that led to communication breakdowns. Participants explained:As health care providers, we always want to look for the pain in the patient instead of listening to what the patient has to say (Nurse)Healthcare providers perceived patients misrepresent the severity of their pain, and they believed pain medication was misused (SC 8). Participants explained that they often did not believe patients’ reports of the pain experience (SC 8):… health care providers being the experts in health-related issues, do not want to listen to what the patient has to say, and if they do not listen, how much pain they are experiencing, then it is difficult to manage the cancer pain because what gauge will they use? (Doctor)Two institution-related barriers were identified: resource limitations, and a lack of standards and guidelines for pain management.With specialized training, our patients can receive the quality care they deserve. (Doctor)Participants indicated that there needed to be more funding for healthcare providers’ capacity-building (SC 9). They expressed the value of specialized training in improving the quality of health services provided to patients at a specialized hospital as follows:Enough funding should be allocated for specialized training, for example, palliative care, oncology. (Nurse)We have limited types of pain medication … Certain cancer pains are complex and need complex drug combinations, but we are failing our patients in that regard (Doctor)Participants also mentioned medication shortages (SC 10) as a barrier to cancer pain management:Cancer is complex, and we need a completely specialized team to manage it. (Doctor)In addition, participants explained that due to the complexity of cancer pain, it should be managed by a multidisciplinary team; however, in this context, there were a limited number of multidisciplinary team members (SC 11) involved in treating patients with cancer. As explained:Our poor patients do not have the means to be moving back and forth to this distant hospital just for pain medication. (Nurse)The government need to build more of such hospitals in various country locations to carter for the majority. (Doctor)Participants also indicated that patients could not access specialized services as they were centralized at one hospital (SC 12):As a hospital, we do not have standards and guidelines that suit our setting and drug availability levels …. Each one prescribes according to their level of knowledge and experience. (Doctor)Some participants expressed concern about the hospital's lack of standards and guidelines for assessing and managing cancer pain (SC 13). Guidelines are crucial and impact uniformity in treating patients with cancer when they are in pain. Participants shared that:What we are lacking is displayed standards and treatment guidelines in pain control, internationally recognized standards and guidelines like the World Health Organisation on cancer pain management which may need to be adopted and adapted to our setting. (Nurse)Based on the study's objective to explore and describe healthcare providers’ perceptions of the cancer pain management barriers at a hospital in Zambia, three themes emerged: patient-related barriers, healthcare provider-related barriers and institution-related barriers. The study's results reflect the multidimensional nature of barriers to cancer pain management, and these were also found in similar studies in a variety of other settings .In this study, healthcare providers perceived patients’ specific characteristics, namely their financial constraints, multiple illnesses, medications, and beliefs, as barriers to cancer pain management. Financial constraints affect patients’ ability to travel to healthcare facilities, negatively impacting the continuity of care. The findings that compliance with cancer treatment was related to the distance patients had to travel and the high costs associated with the travel and services are confirmed by other studies .In this study, managing multiple illnesses with various medications impacted adherence to cancer pain management regimens. Similarly, Patients’ beliefs also affect their feelings about cancer pain management and, in turn, their behavior. In this study, two beliefs affecting adherence to cancer pain management regimens and follow-up included the belief that witchcraft was responsible for their cancer, and male patients not reporting pain due to the belief that this reflects weakness. Furthermore, participants’ knowledge was a barrier to cancer treatment. Limited knowledge and misconceptions about pain medications lead to reluctance to report pain and adhere to pain regimens. A perceived healthcare provider barrier was a lack of knowledge and skills in assessing and managing cancer pain. Various studies found that nurses and doctors did not have adequate knowledge about pain assessment and management . Javier Precise assessments and reassessments of the severity, type and cause of pain are essential in developing and implementing a holistic management plan to relieve cancer pain . FurtherAnother finding in this study was that healthcare providers tended to disbelieve patients’ reports of pain. This finding is comparable to those from a previous study, wherein doctors tended to believe that patients overreported their pain more than nurses; as a result, patients complaining of pain were given a placebo .Language limitations were another barrier to cancer pain management in this study. Inadequate communication and listening to patients can lead to adverse psychological outcomes, including dissatisfaction with care, increased anxiety, long-term maladjustment, and an unmet need for symptom management . In ordeBarriers related to limited cancer pain management strategies and guidelines, and a lack of available medication, were mentioned in this study. A strength of the study was that medical doctors and nurses were included in the research sample, leading to the inclusion of the perspective of two categories of healthcare providers and, in so doing, triangulating findings. The inclusion of other healthcare providers’ views would have been valuable to gain a broader perspective of the barriers to holistic and comprehensive pain management.Healthcare providers’ knowledge limitations in the assessment and holistic management of cancer pain require education, training and ongoing capacity-building interventions. Multidisciplinary approaches to cancer pain management should include a culturally sensitive approach that acknowledges patients’ and their families’ beliefs about the cause of cancer, reporting of cancer pain, consequences of opioid use, and complementary and traditional medicine and practices. Furthermore, healthcare providers should be empowered to optimally use existing pain management methods and medications within the resource-constrained environment. Guidelines should also be context-specifically formulated to accommodate resource constraints. Ongoing advocacy for patients’ right to access resources and services to optimally manage cancer pain is required.Effective management of cancer pain can prevent suffering and improve patients’ quality of life. Cancer pain management requires a total pain management approach that addresses the barriers to pain management from a patient, healthcare provider, and institutional perspective. The knowledge deficit among patients and healthcare providers is a barrier to cancer pain management and is one of the most common challenges reported in the literature. Various approaches are required to educate patients, families and society about cancer pain management to reach a wider group. Healthcare provider education, during their studies and ongoing after completion of training, is essential to ensure adequate pain assessment and management strategies. Healthcare providers’ views that cultural beliefs about cancer being caused by witchcraft and the use of traditional medicine and services are barriers to cancer pain management were unique to this study. Advocacy for the availability of cancer pain management as a fundamental human right, also in resource-scarce environments, should be ongoing. The barriers should receive attention in a contextual plan to improve health providers’ management of cancer pain in the specific hospital in Zambia.


P > .05); however, Group A patients had significantly superior VAS and WOMAC scores than Group B patients at 6 and 12 months after treatment. For the single leg stance test, 2-minute walk test, and time up and go test, Group A patients were significantly superior to Group B throughout follow-up (P < .001). The leg swing and quadriceps strengthening exercises resulted in a significantly better clinical outcomes than the combined PRP and HA therapy, with a sustained lower pain score and improved quality of life, balance ability, and functional activity within 12 months.The aim of this was to investigate the efficacy of physical exercise (leg swing and quadriceps strengthening exercises) versus platelet-rich plasma (PRP) and hyaluronic acid (HA) combination therapy. From January 2020 to August 2021, 106 patients with Kellgren–Lawrence Grade I–III knee osteoarthritis were divided into leg swing and quadriceps strengthening exercises (Group A) and intra-articular combination injections of PRP and HA (Group B) according to the treatment strategies. Patients in Group A received regular leg swing and quadriceps strengthening exercises for 3 months. Patients in Group B received 2 intra-articular combination injections of PRP (2 mL) and HA (2 mL) every 2 weeks. The primary outcome measures were the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities (WOMAC) score. Secondary outcomes included single leg stance test and functional activity by 2-minute walk test and time up and go test. All outcomes were evaluated at baseline and again 1, 3, 6, and 12 months. The VAS and WOMAC scores were similar in both groups at 1 and 3 months after treatment ( Patients with mild to moderate KOA  can often be managed with nonsurgical strategies. Currently, with the confirmation of the nephrotoxicity and side effects of oral non-steroidal anti-inflammatory drugs and corticosteroids, intra-articular platelet-rich plasma (PRP) and/or hyaluronic acid (HA) injections and physical exercise have become a potential alternative option for the treatment of KOA.–7Knee osteoarthritis (KOA) is one of the most prevalent musculoskeletal diseases and a leading cause of joint pain, stiffness, and increasing disability. It is mainly accompanied by articular cartilage injury, joint margin degradation, subchondral bone hyperplasia, cyst formation, muscular dystrophy, and weakness.,8 Autologous PRP is an autologous and multifunctional platelet concentrate from the blood that can release macrophages and growth factors after activation, stimulate the cartilage healing process, and improve the damage caused by joint disease.,10 HA is a glycosaminoglycan that can lubricate articular surfaces, transport nutrients, repair degraded articular cartilage, and further delay joint degeneration of the knee.,12 Several studies have demonstrated the efficacy of intra-articular PRP combined with HA injections in the treatment of KOA with promising clinical outcomes.,6,8 The combination injections of PRP and HA seem to have a synergistic effect and can better improve the pain and functional status of patients than PRP or HA alone.,14PRP and HA, as commonly used drugs for intra-articular injection, have been proven to be effective treatment strategies for KOA.,16 Currently, common physical exercise for patients with KOA includes swimming, walking, quadriceps strength training, leg swings, Tai Chi, cycling, yoga, or other forms of exercise. In clinical practice, the authors found that leg swing and quadriceps strengthening exercise for patients with KOA have better safety and economic benefits than other exercise methods, which can improve knee joint function of the knee, improve the health status of life, relieve pain, and delay knee cartilage degeneration. Therefore, the aim of this study was to investigate the efficacy of leg swing and quadriceps strengthening exercises versus the combination of PRP and HA injection in patients with KOA.Many documents illustrate that exercise therapy is widely used in the conservative management of KOA, and that moderate physical exercise can effectively improve pain, functional activities, quality of life, and psychological health in KOA patients.This study was designed as a retrospective study, and was performed following the ethical standards of the 1964 Declaration of Helsinki and later amendments. The study protocol was approved by the local ethics committee of our hospital . The study had been retrospectively registered on Protocol Registration and Results System clinicaltrials.gov (ID: NCT05585216). Written informed consent was obtained after sufficient explanation was provided to all patients.; (3) patients with a K–L grade for KOA of I–III; and (4) a history of symptoms for more than 3 months and patients with independent mobility. Exclusion criteria included the following: (1) lower limb axial deviation >5° ; (2) patients with diabetes mellitus, severe cardiovascular disease, immunosuppressive status, mental illness; (3) injections or other invasive treatments of the lower extremities were used in the previous 3 months; (4) patients who were willing to undergo exercise training under the medical supervision; (5) patients with previous fractures or bone tumors of the ipsilateral lower limb; (6) patients who received previous hip or knee joint surgery; (7) patients who had participated in standardized lower limb exercises strengthening within the previous 3 months; and (8) patients who did not complete the regular follow-up. For patients with bilateral KOA, the more severely affected side . If the K–L grade of the bilateral knees was the same, the right side was included in the study.A total of 150 patients with painful KOA who received conservative treatment from the joint surgery outpatient department of our hospital between January 2020 and August 2021 were included. The inclusion criteria were as follows: (1) patients aged ≥ 45 years; (2) KOA diagnosed according to the American College of Rheumatology Classification CriteriaFinally, 106 (70.7%) patients with K–L Grade I–III KOA were enrolled, and 44 patients were lost to follow-up. According to the treatment strategies, 106 patients were divided into 2 groups: patients in Group A were treated with leg swing and quadriceps strengthening exercises (3 months); patients in Group B were treated with intra-articular combination injections of PRP (2 mL) and HA (2 mL) every 2 weeks. The affected knees were injected under ultrasound guidance at 30° of flexion. Injections were performed using a strictly sterile lateral mid-patellar approach. The HA was 2.0 mL (20 mg HA) of high molecular weight  non-cross-linked HA extracted from bacterial cells (Eufflexa-Ferring 10 mg/mL HA), as shown in Figure  For the quadriceps strengthening exercise, the ankle joint of the affected side was held in plantar flexion in a neutral position, the knee joint was extended to 0°, and then the leg was slowly raised until the heel was 25 to 30 cm away from the bed, held for 5 to 10 seconds and then slowly lowered to the supine position. They were required to raise their leg approximately 200 times per day  for 15 minutes at room temperature, and 4 mL of PRP was obtained using a general-purpose centrifuge (Regen Lab). This was leukocyte-rich plasma and PRP according to the Dohan Enrenfest et al Classification.,19,20 Secondary outcomes included the single leg stance test (SLS) and functional activity using the 2-minute walk test (2MWT) and the time up and go test (TUGT).,15 All outcomes were assessed at baseline and at 1, 3, 6, and 12 months.In the present study, the participants will be followed for at least 12 months. Before and after the treatment, observers measured pain severity, health status of life, balance ability, and functional activity. The primary outcome measures were the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities (WOMAC) scores. The unaffected leg does not touch the supporting leg and remains balanced for as long as possible. Three trials were performed for each patient, and the best result of the 3 trials was recorded. Functional activity was evaluated using the 2MWT and TUGT at baseline and 1, 3, 6, and 12 months after treatment. The 2MWT is the distance the patients can walk in 2 minutes, with or without a walking aid. TUGT is the time patients need to get up from the same chair, walk as far as they can in a straight line for 3 meters, and then sit back down on the chair.Pain severity was evaluated by VAS score . Quality of life was assessed by the WOMAC total score. The scale consisted of 8 indicators that determined the patient’s assessment of their physical performance. SLS is the time spent standing with the unaffected knee flexed and the affected leg supported, and is an important predictive parameter for assessing balance ability.U test was used for continuous data, and the chi-squared test was used for categorical data. A P-value < 0.05 was considered statistically significant.Statistical analyses were performed using IBM SPSS Statistics Version 22.0 . The Kolmogorov–Smirnov test was used to check the normality of data distributions. Continuous variables are expressed as the mean and standard deviation, and categorical variables are expressed as numbers and percentages (%). The Mann–Whitney P > .05). No patients in either group experienced any adverse events during treatment.Of the 150 participants, 106 patients  met the screening criteria and were divided into either the physical exercise group (n = 51) or the combined-injection group (n = 55). No patients were lost to follow-up during the study period. Demographic and clinical characteristics are shown in Table P < .001). We then assessed the effects of the 2 treatment strategies on balance ability and functional activity in patients with KOA. Both groups showed significant improvements in knee strength at each follow-up period compared to baseline. The data also indicated a greater percentage of knee balance ability and functional activity between the 2 groups. At 1 month after treatment, patients who received PRP injection combined with leg swing and quadriceps strengthening exercise had a significant advantage in SLS, 2MWT, and TUGT (P < .05). There was also a tendency towards increased differences in SLS, 2MWT, and TUGT between groups at 3, 6, and 12 months after treatment was observed (P < .001).As shown in Table Notably, Group A showed significant improvements from baseline in pain intensity, quality of life, balance ability, and functional activity at each follow-up period, and the improvements were maintained after 6 months. In Group B, all primary and secondary observer measures improved significantly at 3 to 6 months, with maximal improvement was at 3 months, but he effects gradually diminished thereafter Table .This study compared the efficacy of physical exercise versus intra-articular PRP combined with HA injection for patients with K–L Grade I–III KOA. We found that the leg swing and quadriceps strengthening exercise group and intra-articular PRP combined with HA injection both improved pain, quality of life, balance ability, and functional activity in patients with mild to moderate KOA. However, the improvements in the leg swing and quadriceps strengthening exercise group were more significant than those in the intra-articular PRP combined with HA injection group and were maintained after 6 months. Treatment of KOA includes nonsurgical treatment, such as weight loss, exercise, physical therapy, analgesic drugs, injections of HA and PRP, and surgical treatments. However, previous studies have shown that long-term use of non-steroidal anti-inflammatory drugs and analgesic drugs may cause nephrotoxicity and gastrointestinal side effects, as well as dependence, and lead to accelerated loss of knee function. Physical therapy can temporarily relieve pain and restore function, but it cannot maintain the effect for a long time.KOA is a degenerative disease with clinical manifestations including joint pain, stiffness, joint swelling, restricted movement, and joint deformities.,6,8,13 In addition, some evidence suggests that physical exercise, as a safe and non-pharmacologic intervention for KOA, can also improve patient outcomes related to symptoms, quality of life, and functional activity.,17,20 Exercise therapy can prevent muscle atrophy, treat and prevent pain, and improve lower limb motor function. The most commonly used physical exercises include quadriceps strengthening, leg swings, and hip abductor strength training. A number of studies have found that leg swing and quadriceps strengthening exercises may have a potentially positive effect on cartilage repair, significantly improving joint function, reducing humoral and cellular immune responses, and promoting angiogenesis, thereby improving histological parameters.,26 In our study, leg swing and quadriceps strengthening exercises were shown to be an effective in the treatment of mild-to-moderate KOA and was superior to PRP combined with HA injection. These findings suggest that leg swing and quadriceps strengthening exercises may be a potential treatment option for patients with KOA in the future.In recent years, the clinical application of intra-articular PRP and HA injection for the treatment of mild to moderate KOA has become increasingly frequent, and its therapeutic effect has been widely reported. demonstrated that PRP combined with HA injection was effective in alleviating pain symptoms and WOMAC scores at 30 and 90 days after application. Consistent with our findings, intra-articular PRP combined with HA injection significantly improved the VAS score and WOMAC score total at 1 and 3 months compared with baseline data, but the improvement gradually diminished after reaching a peak at 3 months. Notably, there was no difference in the VAS and WOMAC scores of patients who received leg swing and quadriceps strengthening exercise compared with patients who received combined intra-articular injection of PRP and HA at 1 and 3 months after treatment. However, with longer follow-up, the advantage of exercise therapy in improving knee pain and quality of life gradually emerged (P < .001).Clinically, VAS pain and WOMAC total score are commonly used to evaluate symptom relief and quality of life improvement in patients with KOA. Lana JF et al Considering that the lower limb represents a whole chain of motion, studies investigating the effects of physical exercise on patients with KOA have mainly focused on quadriceps strengthening, hip joint peripheral muscle strengthening, and leg swinging. Some scholars have suggested that quadriceps strengthening exercises may be an effective way to prevent and treat KOA, which could reduce pain and restore stability and function.,19,20,27 Meanwhile, some recent studies have found that leg swing exercise can reduce pain and improve the overall function of patients with KOA by strengthening the hip abductor muscle strength and reducing knee joint loading. In patients with KOA, pain and muscle wasting are associated with limited knee function. Chronic pain causes behavioral avoidance and increases muscle wasting. In addition, improvements in muscle strength, proprioception, and balance can have a major impact on lower limb mobility performance.The latest KOA guidelines have given considerable attention to exercise rehabilitation and sports promotion strategies in disease management. performed quadriceps strengthening exercises on patients with KOA for 6 months and found that joint pain was effectively relieved, VAS score was reduced by 22.5%, and the physical function score was significantly improved. Sun et al published a study evaluating SLS in patients with KOA after treatment with a combined injection of PRP and HA. The findings suggested that decreased lower limb muscle strength and proprioceptive deficits in KOA may affect effective and timely motor responses to maintain balance. In addition, Bokaeian et al used the 2MWT and TUGT to assess knee functional activity in patients with KOA after quadriceps strengthening training. The results showed that quadriceps strengthening training significantly improved the mean changes in knee functional activities, which was consistent with our findings. Our study showed that the SLS, 2MWT, and TUGT tests in patients who underwent leg swing and quadriceps strengthening exercise were significantly better than those in the combined injection group (P < .05) at 1, 3, 6, and 12 months after treatment. Our results suggest that the synergistic effect of leg swing and quadriceps strengthening exercise may be better than that of PRP combined with HA injection, but the specific mechanism remains unclear.The SLS, 2MWT, and TUGT tests are objective clinical tests of standing balance and functional activity. O’Reilly et alSeveral limitations to this study should be noted. First, this was a single center retrospective study, and the sample size was small. Only patients with K–L Grade I–III KOA were recruited. Secondly, the combined intra-articular injection volume was twice that of the single-injection groups. The larger volume may lead to overexpansion of the subcutaneous fascia, which may affect the observed results. Third, instead of systematically measuring balance ability and functional activity, we used indirect scoring tests to reflect the treatment effect. Finally, patients received different combination therapies, which could also affect the results.The present study showed that leg swing and quadriceps strengthening exercises had a better clinical effect than PRP and HA combined therapy in patients with mild to moderate KOA. Leg swing and quadriceps strengthening exercise could significantly improve pain, quality of life, balance ability, and functional activity and maintain these improvements over 12 months. With exercise as part of a comprehensive treatment programme, we hope that our therapy will be the first choice for the patients with KOA.Data curation: Xuejing Li, Ying Pan, Guoqiang Liu.Formal analysis: Xuejing Li, Xiaoyang Zhang, Kunfeng Duan.Methodology: Cong Ma, Suhui Qie.Project administration: Suhui Qie.Supervision: Ying Pan, Hua Tian, Xiaozuo Zheng.Writing – original draft: Cong Ma.Writing – review & editing: Ying Pan, Zhongzheng Wang, Suhui Qie.