Little is known about patients’ intention for participation in end-of-life decisions (EOLD) in three coastal provinces in southern China. This study aimed to explore the willingness of patients with cancer pain to participate in EOLD and potential influencing factors.A multi-center cross-sectional study was performed in three coastal provinces in southern China. Two hundred and thirty patients with cancer pain were recruited and consented to fill out the questionnaires. The patients’ willingness to participate in EOLD, demographic and disease-related data was surveyed.P <  0.05). Finally, a predictive model combined above five factors was established, which showed a good discrimination  and calibration  for which patients more willing to participate in EOLD.In total, 223 patients completed and returned the survey (response rate = 96.95%). One hundred four cases (46.64%) were willing to participate in EOLD. 119 (54.36%) cases not willing to participate in EOLD, respectively. Multivariate logistic regression analysis shows that educational level , history of alcoholism , Eastern Cooperative Oncology Group (ECOG) score  and experience of explosive pain  and clinical rescue  had significant effects on EOLD intention (The willingness of patients with cancer pain to participate in EOLD is at a modest level in three coastal provinces in southern China. Patients with lower educational level, history of alcoholism, better health status and experience of explosive pain and clinical rescue may be more prone to participate in EOLD.The online version contains supplementary material available at 10.1186/s12904-022-01108-x. Cancer-related pain, reported by more than 70% of patients, is one of the most common and troublesome symptoms, which can occur at different stages of cancer. Despite the continuous optimization of analgesic treatment strategies, cancer-related pain may be inadequately controlled in up to 50% of patients . Pain doEnd-of-life decisions (EOLD) (including advance directives (ADs), do not resuscitate/do not intubate, last wishes and so on) are unavoidable topics that all palliative care physicians, patients, and their caregivers must face . In the Although some studies focused on the preference of EOL care and cancer patients’ and caregivers’ decision-making practices in China mainland –16, littThis study was a cross-sectional study, which carried out in three tertiary cancer hospitals  in Southern China because the tertiary cancer hospital is a provincial cancer treatment center, which can accept cancer patients from all regions of the province . This study was reviewed and approved by the centralized ethics committee of Fujian Cancer hospital (SQ2018–039-01). The data collection was completed between August 2020 and December 2020.Potential eligible in-hospital patients with cancer pain were screened according to the following inclusion and exclusion criteria. The inclusion criteria were: (1) age ≥ 18 years old, with good language communication skills; (2) patients with malignant tumor diagnosed by histology or pathology; (3) NRS  ≥ 1 point during treatment; (4) mental stability; (5) voluntarily participate in this study under the principle of informed consent. The exclusion criteria were: (1) not answer or not fill in the questionnaire, (2) those patients who have unstable vital signs. The questionnaire used in this study contained 20 items. Ten participants per item were adopted to guide the sample size calculation according to an epidemiological method previously reported . The estThe questionnaire of willingness to participate in EOLD was designed based on consulting relevant literature . The queBefore performing this investigation, data collectors were trained on what EOLD is and how to interpret the purpose, process and potential benefits / risks to the participants to ensure the quality of data collected. Five trained collectors screened the eligible patients from the in-hospital patients with cancer pain according to the inclusion and exclusion criteria. Then, the data collectors would explain the definition of EOLD and relevant survey information to the potential participants and invited them to participate in the current study. After the patients fully understood the meaning of the questionnaire and agreed to participate in this study, they were required to sign a written informed consent. For those patients who have difficulty in writing, the patient’s family signed the written informed consent on behalf of them. After obtaining the informed consent from each participant, the data collectors guided the patients to complete the questionnaire in the form of face-to-face interviews.P value < 0.1 in univariate analysis were further included in multivariate logistic regression model and analyzed using a backwards model selection procedure (elimination criterion: p > 0.05) [P value < 0.05 that were utilized to build the final predictive model. The receiver operating characteristic curve (ROC), calibration plot, and Hosmer-Lemeshow test were used to validate the discrimination and calibration of the model. Statistical tests were performed using the SPSS version 22.0 . All P values were two-tailed, and statistical significance was set at P <  0.05.The normal distribution of outcome variables was confirmed using the Kolmogorov–Smirnov test. Categorical variables were expressed as percentages and compared with the Chi-Square test. Continuous variables were presented as mean and standard deviation, and compared by using the independent-sample Test or Mann–Whitney U test. 95% confidence intervals (95% CI) were calculated for the median length. First, univariate logistic regression was used to measure the independent relationships between willingness to participate in EOLD and each predicting variable. Then, factors with a  > 0.05) . FinallyThe basic information of patients was shown in Table P > 0.05). The patients in the group willing were older than the group unwilling . More patients in the group unwilling have ever accepted a relative higher-level education with a proportion of 33.3% for high school or above . However, more patients in the group willing had a history of alcoholism when compared with the group unwilling . The ECOG score of the patients in the group willing was less than that of the group unwilling . In terms of pain, 81.7% of patients in the group willing have ever experienced an explosive pain, which was significantly more than the group unwilling . The daily dose of opioid analogues of patients who were willing to participate in EOLD was significantly higher than that of group unwilling . The proportion of pain in the group willing due to disease deterioration, improper use of analgesics and others was 41.4, 24.0 and 34.6%, respectively. Conversely, the proportion of pain in the group willing due to disease deterioration, improper use of analgesics and others was 46.2, 37.0 and 16.8%, respectively. There was significant difference between two groups (P = 0.006). In addition, in the group willing, there were more patients had an experience of clinical rescue when compared with the group unwilling .The patients of group unwilling were composed of those who refused to and did not sure whether to participate in EOLD. Finally, 104 patients (46.6%) were willing (group willing) and 119 patients (53.4%) unwilling (group unwilling) to participate in EOLD, respectively. The detail comparison was showed in Table P = 0.002), educational level , P = 0.003), previous alcoholism , P <  0.001), ECOG score , P = 0.03), experience of explosive pain , P <  0.001), cause of pain outbreak , P = 0.018), and experience of clinical rescue , P <  0.001). In addition, the living area , P = 0.058) and daily dose of opioid analogues , P = 0.064) had a slight impact on whether the patients are willing to participate in EOLD. After incorporating the above nine indicators with P <  0.1, the multivariate analysis showed that only five variables were independent predictors whether the patients with cancer pain are willing to participate in EOLD, including higher educational level , P = 0.031), previous alcoholism , P <  0.001), lower ECOG score , P = 0.017), experience of explosive pain , P <  0.001), and experience of clinical rescue , P = 0.001). Finally, a predictive model equation containing the above five variables was built as Logit (P) = − 0.431 - 0.382* + 2.123* – 0.438*(ECOG score) + 1.851*(experience of explosive) + 1.346* , and used to calculate the probability that the patients were willing to participate in EOLD. The ROC analysis for the probability that the patients with cancer pain are willing to participate in EOLD showed that the area under curve was 0.849   EOLD intention of patients with cancer pain was modest with a proportion close to 50%; (2) educational level, history of alcoholism, ECOG score and experience of explosive pain and clinical rescue are independent predictors of willingness to participate in EOLD, and use of a predictive model including above five factors can well discriminate which patients are willing to participate in EOLD; (3) the EOLD maker that a majority of participants preferred was spouse but not their own, only about one-third of patients were clearly willing to accept aggressive life-support therapy, and a majority of participants (72.1%) preferred to die at home.Currently, advanced care planning (ACP) has been regarded as an effective method in facilitating patient-centered EOL care in the worldwide, which articulates the autonomy of patients’ wishes, values, and goals relevant to their current and future health care , 21. In On the contrary, very few patients with cancer (2.8 to 18.8%) participated in the process of EOLD in China mainland , 15. SucIn order to provide a high-quality EOL care for cancer pain patients, it is of important clinical significance to identify which patients are more willing to participate in EOLD. So, we further analyzed its related influencing factors. Univariate logistic regression analysis showed that age, educational level, ECOG, history of alcoholism, whether they had experienced explosive pain or clinical rescue, and cause of pain outbreak were the main factors affecting the willingness to participate in EOLD. Although there were significant differences in age and cause of pain outbreak between the patients who willing to participate in EOLD or not, multivariate analysis indicated that both age and cause of pain outbreak are not independent predictors for patients have willingness to participate in EOLD. This was accordance with the results from previous studies , 33. In P <  0.001) and calibration  for which patients more willing to participate in EOLD. Thus, such model may be helpful for us to improve patients’ knowledge of EOLD and to provide EOL care in line with patients’ wishes in the clinical practice. Of course, it is undeniable that our study also has certain limitations. First, only few hospitals were included in the survey, which may lead to the result bias. Second, our results only reflect the patients’ willingness at the time of the survey. The patient’s attitude towards whether to participate in EOLD consultation may be shifted over time or with his own health status. Finally, we did not further analyze the reasons why some patients were not sure whether to participate in EOLD. Therefore, it is required to conduct a large-sample longitudinal study addressing on these issues above in the future.Simultaneously, we also found that a history of alcoholism and whether they had experienced explosive pain or clinical rescue were associated with willing to participate in EOLD. The willingness to participate in EOLD in patients with a history of alcoholism is 8.353-fold higher than those patients without history of alcoholism. The patients who have experienced explosive pain and clinical rescue have stronger willingness to participate in EOLD than those who have not experienced explosive pain and clinical rescue, with 6.367-fold and 3.844-fold higher, respectively. On the one hand, continuous excessive drinking is more easily to damage organs and tissues, perception, cognition, emotion and behavior . Such paOur findings suggest that the willingness of patients with cancer pain to participate in EOLD is at a modest level in three coastal provinces of southern China. Some factors including demographic and clinical characteristics influenced such willingness. This study highlights the importance of considering the above factors when making EOL care plans for patients with cancer pain, which will be helpful to improve their quality of life in the EOL stage.Additional file 1.


ObjectivesCurrently, very little literature exists regarding the "fifth vital sign" in pediatric orthopedics, pain. Multiple studies have highlighted the utility of non-narcotic pain medications in treating acute pain. The objective of this study is to determine the type and amount of pain medication(s) administered and subsequently prescribed to pediatric patients ages six months to five years old with femur fractures treated with spica casting in the ER (emergency room) and OR (operative room). We also determined the incidence of spica cast change necessary for the two groups as a secondary outcome.MethodsA retrospective review was completed at a single level 1 pediatric trauma center, evaluating 82 patients who met the inclusion criteria between six months to five years of age with isolated femoral shaft fractures requiring intervention at one institution. Descriptive statistics and Wilcoxon Rank-Sum or Fisher'sFisher's Exact test were used to assess differences between OR and ER groups for either continuous or categorical variables, respectively. The electronic medical record was then queried for demographic information, location of spica cast placement, hours in the hospital, and amount and type of analgesic medications administered and prescribed.ResultsOverall, we noted a preponderance of femur fractures in young males (72%), with the mean age of our cohort being 2.3 years old. Our patients spent a median of 20.9 hours in the hospital and had a median worst pain score of 7/10 during their hospital stay. No difference was found between standardized amounts of morphine equivalent administration between groups in the hospital. Upon discharge from the hospital, most patients received opioid and acetaminophen prescriptions (72% and 83%), but few received an ibuprofen prescription (24.4%). More spica casts placed in the ER needed to be revised in the OR compared to spica casts placed in the OR .ConclusionsThere are various medication regimens for patients with femoral shaft fractures treated with spica casting at one institution. Our study revealed that patients received more prescription opioids if treated in the OR. Additionally, spica casting in the ER did not significantly decrease hospital stay, and it significantly increased the risk of needing a reduction in the OR in our institution. Very little literature exists regarding the "fifth vital sign" in pediatric orthopedics, pain. Pain assessments became as important as the other four vital signs in the mid-1990s following publications from the American Pain Society and validation by Joint Commission evaluations. They standardized the approach to pain management by requiring adequate charting of pain scores both initially and after treatment . With goMultiple studies have shown non-narcotic pain medications, especially non-steroidal anti-inflammatories (NSAIDs) such as ibuprofen, to be equal to or better than codeine or oral morphine for controlling pain associated with fractures in children -9. TheseFemur fractures comprise 1.6% of all pediatric fractures, with about one-third occurring in patients five years old or younger. Length stable femur fractures in children six months to five years of age are typically treated with a hip spica cast . These aOur descriptive study aims to determine the type of pain medication(s) administered within the hospital and subsequently prescribed to pediatric patients ages six months to five years old with femur fractures treated with spica casting in the ER and OR.Following review by the Institutional Review Board (IRB) granting an exemption status, a retrospective review was completed at a single level 1 pediatric trauma center. All patients (109) with isolated femoral shaft fractures requiring intervention at one institution were retrospectively identified from 2013 to 2018. Participants were included if they were between 6 months and five years of age, sustained an isolated femur fracture confirmed radiographically and underwent spica cast placement (82). Patients were excluded if they sustained multiple injuries, were outside the given age range, or were not initially treated with spica cast application. These patients were divided into two groups: 21 patients underwent cast placement in the ER, and 61 patients underwent cast placement in the OR.The electronic medical record (EMR) was queried, and the following demographic information was collected for each patient: age, gender, mechanism of injury, associated diagnoses, and fracture characteristics. The location of spica cast placement was recorded, and the attending orthopedic surgeon typically oversaw treatment decisions. Casts were applied by various trainees (residents to fellows), usually without supervision in the ER and typically with attending physician supervision in the OR. The Cast technique was determined by the provider applying the cast and not recorded for this study. The combined orthopedic team dictated discharge planning, and one of the team members typically taught car seat teaching after spica cast application was administered prior to discharge.We calculated the number of hours spent for each patient, from the presentation to the discharge time. The amount and type of analgesic medications were recorded throughout the patient stay. Pain scores were documented on a 0-10 scale by nursing staff with no particular standardization protocol in place. The Faces Pain Scale augmented this scale for nonverbal children to extrapolate a numerical value. Opioid administration was measured, and the measurements were standardized across patients by converting opioids administered to morphine equivalent (Meq) units and dividing by patient weight and hours in a hospital, resulting in Meq/g/hr.Data analysisDescriptive statistics overall and by location (ER vs. OR) were performed. For continuous variables, the median and 25th -75th percentiles were calculated. Counts and percentages were calculated for categorical variables. Wilcoxon Rank-Sum or Fisher'sFisher's Exact test was used to assess differences between OR and ER groups for either continuous or categorical variables, respectively. Alpha of 0.05 was used to determine statistical significance.Of the 109 patients identified with isolated femoral shaft fractures, 27 were excluded based on the above criteria, making 82 patients available for analysis. Demographic and descriptive statistics with statistical test results between the two groups are shown in Table Overall, we noted a preponderance of femur fractures in young males (72%), and the median age was 2.3 years. Most injuries resulted from a fall (67%), and the fewest from non-accidental trauma NAT (7%). Eleven patients (13%) had a diagnosis potentially predisposing them to a femur fracture. Most fractures followed a spiral fracture pattern in the midshaft of the femur, though there was some variety in our particular patient population in location and type. Our patients spent a median of 20.9 hours in the hospital and had a median worst pain score of 7/10 during their hospital stay. Medication administration showed a wide variety of opioid administration patterns. Patients received between 0 and 58.3 Meq/g/hr. The median, 25th, and 75th percentiles were 9.8, 5.1, and 16.9, respectively. Upon discharge from the hospital, most patients received opioid and acetaminophen prescriptions (72% and 83%), but few received an ibuprofen prescription (24.4%).The OR and ER groups were similar in demographic data and associated diagnoses. A more significant percentage of distal fractures were treated in the ER, but it was not statistically significant. Significantly more spica casts in the ER returned to the OR than spica casts in the OR . The OR group trended toward spending more time in the hospital at 21.6 hours, whereas the ER group averaged 19.9 hours (P = 0.19).No difference was found between standardized amounts of morphine equivalent administration between groups in the hospital. There was, however, a significant difference between opioids prescribed at discharge between groups, with a more significant percentage of patients in the OR group prescribed opioid-type medications . They also trended toward receiving more acetaminophen-type prescriptions p=0.17). Overall, very few patients in both groups were prescribed ibuprofen. Figure 7. OveralThe national opioid crisis is a severe health crisis that affects all levels of patient care, including the individual, family unit, public health sphere, and social and economic welfare. One hundred twenty-eight Americans die daily from opioid overdose, and the CDC estimates the economic burden of prescription opioid use as $78.5 billion per year. Therefore, over the past few decades, the U.S. Department of Health and Human Services and the National Institute of Health have shifted focus on decreasing opioid prescriptions for pain . DespiteIn the U.S., femur fractures are the third most common lower extremity fracture and the most common orthopedic injury requiring pediatric hospitalization. Despite formal guidelines regarding femur fracture treatment, there is no consensus on the best treatment due to age, fracture pattern, mechanism, and associated injury . CurrentThe demographic makeup of our patient group fits that most commonly described in these studies: a preponderance of male gender of walking age. Most injuries resulted from a fall, which is also consistent with described mechanisms mentioned above. Eleven out of 82 patients had an associated diagnosis that could increase their risk for a femur fracture. We initially anticipated that these would be associated with spica placement in the OR; however, we determined this was not necessarily the case as they were not statistically related.Although the majority of femur fractures are isolated injuries due to trauma, they can also be associated with polytrauma and child abuse, especially in infants. A meta-analysis by Wood et al. found a substantial risk of non-accidental trauma (16.7% - 35.5%) in infants < 12mo old with a femur fracture. This risk decreased substantially (1.5% - 6.0%) once the child reached walking age . Our parNew literature has recently emerged regarding opioids for orthopedic surgery, though the amount of pediatric-related literature is scant. Chen et al. released evidence that patient-specific opioid tapers can decrease the number of postoperative opioids administered following several different opioid procedures without untoward perceptions by the patients . AdditioOur study did not determine the amount taken after hospitalization but the amount prescribed following discharge. Interestingly, we found a significant difference in opioid prescriptions between groups. This may have resulted from different providers administering different prescriptions, given no protocol. Acetaminophen was prescribed 83% of the time, but ibuprofen was only prescribed 24% of the time. These may be somewhat confounded due to providers simply instructing patients to take over-the-counter medications. We were surprised at the lack of ibuprofen prescriptions nonetheless, given the safety and efficacy of the medication to decrease opioid intake demonstrated by multiple randomized trials . Pain scThere was no difference between groups in terms of morphine administered in the hospital based on our standardized morphine equivalency calculations. There was subsequently no difference in the number of hours in the hospital between groups. The median number of hours in the hospital for our cohort was 20.9. Performing spica casting in the ER did not correlate with a significantly decreased hospital stay but was significantly correlated with a return to the OR. This could be a function of trainees (fellows and residents) applying the cast or the lack of adequate supplies, fluoroscopy, academic help, or appropriate sedation within the emergency department setting.Additionally, we did not analyze the indications for returning to the OR, which could have differed among providers. Our current protocol does include the application of casting in the ER. Mansour et al. provided a retrospective review that demonstrated comparable complication rates between OR and ER spica cast application; however, ER application resulted in less time for spica placement, fewer hours in the hospital, and decreased hospital charges . We did Limitations to our study include those associated with a retrospective review of the medical record. It is somewhat tricky overall to ascertain the validity of the recorded information, especially related to the timing and accuracy of medication administration and prescription provision. Additionally, there is no standardized protocol within our institution involving analgesia administration, and some patients even undergo evaluation by a pain service, which could confound the study. Further, providers will occasionally recommend over-the-counter analgesia therapy without providing a prescription, which could confuse the overall prescription counts. Also, it is essential to note that prescription administration does not correlate with medications taken at home, which we did not study. We did not record many aspects of patient care for this study, including patient or radiographic outcomes, pain scores at home, or the indications for returning to the OR.Our study demonstrated that pain medication administration during hospitalization and provision of discharge prescriptions varied widely in a retrospective study performed at one institution. This discovery warrants additional prospective studies regarding pain medication administration and further non-opioid alternatives to add to an institution's arsenal for managing pain associated with musculoskeletal pathologies. Despite literature revealing NSAID efficacy and a good safety profile, this has not translated to increased utilization of NSAIDs either during hospitalization or upon discharge at our institution. Our goal is to develop literature-based pain management guidelines and implement them prospectively. This will allow us to add to the literature by comparing inpatient and outpatient pain management in a similar patient population undergoing hip spica casting for pediatric femur fractures and other musculoskeletal pathologies.


Total knee arthroplasty (TKA) and total hip arthroplasty (THA) surgeries are among the most common elective procedures. Moderate to severe postoperative pain during the subacute period  is a predictor of persistent pain 12 months postoperatively. This review aimed to examine the available postdischarge pharmacological interventions, including educational and prescribing strategies, and their effect on reducing pain during the subacute period after TKA or THA.We searched seven electronic databases from inception to April 22, 2021. Published randomized controlled trials of adults who underwent TKA or THA and received a pharmacological-based intervention commencing within 1 week after hospital discharge and conducted for up to 3 months postoperatively were compared with any treatment. Two reviewers independently extracted data on the primary outcome, pain intensity. This review was registered prospectively on PROSPERO (ID: CRD42021250384).P = 0.003). Education on analgesic use during multidisciplinary home visits was effective for reducing pain intensity during the subacute period  compared with usual care.Four trials involving 660 participants were included. Interventions included changing analgesic prescribing practices upon hospital discharge and education on analgesic use. Providing multimodal non-opioid analgesia in addition to reduced opioid quantity was associated with lower subacute pain (coefficient –0.81; 95% confidence interval –1.33 to –0.29; Interventions involving the provision of multimodal non-opioid analgesia and education on analgesic use show positive effects on reducing pain intensity during the subacute period after TKA and THA. Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are cornerstone and cost-effective procedures to improve pain, mobility, and quality of life for people with severe knee and hip osteoarthritis, respectively , 2. TKA Adequate pain management after TKA and THA facilitates faster rehabilitation and reduced postoperative complications, hospital readmission rates, and overall health care costs . A prospThe most effective pharmacological-based interventions for subacute pain after TKA or THA have not been established, which represents a gap in evidence for providing care in the subacute postoperative period. Therefore, the present systematic review will examine the available evidence for postdischarge pharmacological interventions, including educational and prescribing strategies, and their effect on reducing pain during the subacute period after TKA or THA.This review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . This reWe included original peer-reviewed randomized controlled trials (RCTs) written in English. We excluded all other study types and conference abstracts.Studies with adult participants (18 years of age or older) who had undergone primary TKA or THA were included. Studies in which analgesics were used exclusively for palliative care, opioid-substitution therapy, or cancer-related pain were excluded, as they were outside the scope of this review.The effectiveness of exercise-based rehabilitation interventions on pain outcomes after TKA or THA has been explored in several systematic reviews. No physiotherapy-based exercise intervention has been found to be clinically superior to another for pain outcomes in the subacute phase after surgery . Thus, wWe extracted relevant measures before and after the intervention, up to 3 months postoperatively. The primary or secondary outcome of the study must have included index joint pain up to 3 months postoperatively.The primary outcome of this review was index joint pain intensity up to 3 months after TKA or THA.Secondary outcomes included postoperative overall body pain, analgesic use , incidence of adverse events, physical function, length of hospital stay, hospital readmission rate, psychological functioning, disease-specific function or quality of life, and overall quality of life collected up to 12 months after surgery. We also collected information on how studies defined the subacute period after surgery.These criteria are shown in the Population, Intervention, Comparison, Outcome (PICO) format in We conducted a systematic search in seven electronic databases: Medline (1960–present), Scopus (1960–present), Embase (1969–present), Cochrane Central Register of Controlled Trials (1995–present), International Pharmaceutical Abstracts (1970–present), PsycINFO (1963–present), and the Cumulative Index of Nursing and Allied Health Literature . The search was conducted from database inception to April 22, 2021.The search terms applied to all electronic databases were developed with an academic librarian and integrated three key filters: postoperative pain management; hip or knee replacement surgery or arthroplasty; and RCTs. The same key terms were applied across all databases with appropriate syntax and subject headings. The full search strategy is available in References of relevant articles were screened to identify additional studies not captured by the search strategy. Where required, we contacted the authors of potentially eligible articles to obtain additional data relevant to this review and not present in the published articles. The gray literature was also searched via Proquest Dissertations and Theses.After the removal of duplicates, two authors (SL and FG) independently filtered articles by title and abstract for potentially eligible studies. Full-text articles were then assessed independently by the same two authors to confirm eligibility. Any discrepancies were determined by consensus with other team members .Two authors (SL and FG) independently extracted data using a standard data extraction form  that incQuality assessment of all included studies was conducted. Four authors  were involved in this process and used the Revised Cochrane Risk of Bias Assessment Tool for Randomized trials (RoB 2) . Five doHeterogeneity among studies was assessed by comparing study design, intervention approach, and outcomes. Because of heterogeneity in interventions and outcomes among studies, a meta-analysis could not be performed. Thus, a narrative synthesis of available studies according to intervention type and our primary and secondary outcomes was conducted.Cochrane Handbook for Systematic Reviews of Interventions [We planned to conduct a Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) analysis to assess the certainty of the evidence for the primary outcome using guidelines outlined in the ventions .The search strategy generated a total of 5,753 articles, of which 73 full-text articles were assessed for eligibility. Refinement by the inclusion and exclusion criteria resulted in four studies  being elOne study was a three-arm, parallel-group, cluster RCT , and theTwo of the four included studies , 20 usedBecause of significant variation in the interventions used and outcome measures between studies, a GRADE analysis was not undertaken.Studies used interventions that could be classified into two categories: 1) prescribing interventions to change analgesic prescribing practices upon hospital discharge (n = 2) , 20, andP = 0.003) and Group B patients  than in the Group C cohort. No significant difference in VAS pain scores was identified between Groups A and B . Significantly lower daily MME opioid use was reported in Group A patients  and Group B patients  than in Group C patients during the 30-day postoperative period. During this period, patients allocated to Group A also reported lower daily MME opioid use than did the Group B cohort . The average MME opioid use in total was 44.8 mg among Group A patients, 79.9 mg among Group B patients, and 109.8 mg among Group C patients at 30 days postoperatively. The time to opioid discontinuation was also shorter in Group A  and Group B  than in Group C (2.57 weeks). Adverse events were assessed with the Opioid-Related Symptom Distress Scale. Patients in Group A reported significantly lower mean Opioid-Related Symptom Distress Scale scores at 4 weeks postoperatively than did Group C patients (P = 0.005). Physical function was assessed with the Hip Disability and Osteoarthritis Outcome Score. No significant between-group differences were reported at 90 days postoperatively (P = 0.86) [Two studies examined the effect of analgesic prescribing interventions at hospital discharge on subacute pain levels after TKA or THA , 20. A t = 0.86) .P = 0.881). However, the authors reported significantly fewer unused opioid tablets at 30 days after hospital discharge among patients given 30 oxycodone 5-mg tablets upon discharge than among those given 90 oxycodone 5-mg tablets upon discharge . Although more patients given 30 oxycodone 5-mg tablets on discharge requested an oxycodone refill prescription within 90 days of discharge than did those given 90 tablets of oxycodone 5 mg on discharge , no significant between-group difference in the proportion of patients receiving a tramadol refill within 90 days of discharge was reported (P = 0.13) [An RCT conducted by Hannon et al.  randomiz = 0.13) .P = 0.02). Patients allocated to receive the personalized pain management smartphone application used 23.2% less opioids  and 14% more paracetamol  than did control subjects at 14 days after hospital discharge. Physical function was assessed with the Knee Injury and Osteoarthritis Outcome Score—Physical Function Short-Form (KOOS-PS) and Oxford Knee Score. No significant differences in KOOS-PS or Oxford Knee Scores between the total pain management mobile phone application group and controls were reported. However, active use of the pain management mobile application among patients in the intervention group  was associated with significantly lower KOOS-PS scores than those of controls at 1 month postoperatively . Finally, no significant between-group differences in quality of life measured by the EuroQol-5 Dimensions 3-level version questionnaire were reported at 14 days after hospital discharge [Two studies evaluated the effect of providing tailored patient education after hospital discharge , 22. An P < 0.001). This study also assessed physical function with the Knee Society Score, knee joint range of motion, and time until the patient could move independently. Patients who received home visits from a multidisciplinary team after TKA reported significantly higher Knee Society Scores , higher Knee Society Functional Scores , greater knee joint range of motion , and reduced time until the patient could move independently  at 6 weeks postoperatively compared with those allocated to the control group [An RCT conducted by Sindhupakorn et al.  comparedThis systematic review identified four trials involving 660 randomized participants in which a pharmacological-based intervention, including educational or prescribing strategies, was conducted during the postdischarge (subacute) period and was tested against usual care for the reduction of subacute pain after TKA or THA. Interventions included changing analgesic prescribing practices upon hospital discharge and providing education on analgesic use during the subacute period through the use of mobile phone applications or during multidisciplinary home visits. Reducing the quantity of opioid analgesics supplied on hospital discharge did not lead to worse subacute pain levels . FurtherPrevious systematic reviews of interventions to reduce pain after TKA or THA have focused largely on acute or chronic pain, with limited research targeting the subacute period. A systematic review by Fischer et al. conducted in 2005 reported that effective interventions for the reduction of immediate postsurgical pain after THA included peripheral nerve block, intrathecal analgesia, and multimodal non-opioid analgesia . A systeEducational interventions are often used for the management of musculoskeletal pain and thus also appear to be relevant during the subacute phase. The studies exploring educational interventions by Pronk et al.  and SindDefinitions of the subacute period vary widely in the literature, ranging from 30 days  to 90 daTo our knowledge, this is the first review to examine the effect of pharmacological-based interventions on reducing pain during the subacute period after TKA or THA. We prospectively registered and adhered to the protocol of this systematic review. Only RCTs were included to improve the reliability of our findings.However, there are several limitations to this study. Although we conducted a rigorous search across seven electronic databases, reference lists of included studies, and the gray literature, the search strategy was limited to articles written in the English language. Thus, relevant articles in other languages may not have been identified. We were unable to conduct a meta-analysis because of the heterogeneous nature of the included studies. As the number of included trials was relatively small, we were also unable to assess for publication bias with funnel plots . FinallyInterventions involving the provision of multimodal non-opioid analgesia, a lower quantity of opioid analgesics, and patient education on analgesic use appear to be effective strategies to reduce pain intensity during the subacute period after TKA and THA. Further high-quality randomized controlled studies with rigorous and comparable study designs are needed to expand on, and quantitatively synthesize, the existing and any newly emerging data.pnac052_Supplementary_DataClick here for additional data file.


Material and method. 27 patients, ranging in age from 35 to 72 years old, 12 males and 15 females, who received dental implants and failed to achieve osseointegration from Tianjin Medical University Second Hospital, were analyzed and studied in the following aspects: bone density, initial torque, one- or two-stage surgery, postsurgical pain, postsurgical swelling, and radiographic evidence of osseointegration failure.  The relationship between postsurgical pain and osseointegration was evaluated and analyzed in this study.  5 patients were assessed to be D4 bone density and 7 cases were assessed to be D3 bone density, 2 patients were assessed to be D2 bone density and 13 patients were assessed to be D1 bone density. All cases were documented with clinically acceptable initial torque. Among the 27 cases, 2 of them were one-stage nonsubmerged surgery and 25 cases were two-stage submerged surgery. 25 out of 27 patients reported moderate to severe pain lasting for more than 72 hours. Radiologic examinations failed to offer any indication of poor osseointegration in the 7-day postsurgical follow-up.  Moderate to severe postsurgical pain lasting more than 72 hours displays high odd ratio of poor osseointegrate. The radiological examinations alone failed to offer any valuable evidence for the early detection of osseointegration failure in this study. Dental implants have become widely utilized in contemporary dentistry for their efficiency, comfort and reliable, and predictable outcomes . HoweverEfforts from the manufacturers  and the However, poor osseointegration cases continue to be encountered and reported occasionally. Medication including antibiotics and micro molecules still remains no significant beneficial effects when managing poor osseointegrated cases .Efforts were made in our group to explore the titration of pain control medication application for the dental implant postsurgical patients and several cases of severe postoperative pain that were reported drew our focus and subsequently resulted in a relatively higher possibility of osseointegrated failure encountering in the following up of those cases. Therefore, 27 cases of osseointegrated failure using Dentium Implants were collected and studied in this case-control study to explore any causal relationship between pain and poor osseointegration outcome.This study was designed to collect 27 patients that encountered dental implant osseointegration failure out of the total 872 patients from the same clinician in Tianjin Medical University Second Hospital between Jan 2018 and Apr 2021. The design and analysis protocols followed STROBE guidelines, and the study was approved by the Ethical Committee of the Second Hospital of Tianjin Medical University.Patients who participated in this study displayed no detectable contraindications of receiving the dental implants, and all the consent forms and necessary blood work had been accomplished prior to the dental implant installation procedure. Excluding criteria include as follows: younger than 18 years of age; inability to fully understand or report the NRS reporting system; females using oral contraceptives, being pregnant or actively breastfeeding; chronic use of bisphosphonates within 3 years prior to the study; uncontrolled periodontitis, TMD, and untreated caries.30 cases of patients with successful osseointegration  were randomly selected and evaluated as the control group and 6 patients among the 30 cases received a bone graft (to reduce the selection bias).All the patients received the Dentium Superline implants following a standard protocol by the same clinician from Tianjin Medical University Second Hospital. All the patients were followed up by phone on the 1st and 3rd days post implant surgery. Sutures were removed on the 7th day post surgery, and the nonsubmerged case patients were also called back for clinical evaluation and X-ray examination. In case of abnormal issues reported, all the abnormal information including nonrelieved moderate to severe pain or severe localized swelling were clearly documented and one additional in-clinic appointment was scheduled on the 14th day post surgery for those patients.All the data from the dental implants osseointegration failure patients including the following aspects were collected and analyzed: bone density classification, initial torque, one- or two-stage surgery, postsurgical pain, postsurgical swelling and radiology indication and fixture removing time. Pain classification was collected and measured by using a questionnaire with the pain classification numerical rating scales (NRSs), and mild pain was defined with a scale of 1–3, moderate was defined as a scale of 4–6, and a severer pain was defined as more than 7 in this study , 16.All the patients were checked to report the pain score number describing the pain for blood taking procedure in order to test the bias of NRS evaluation. 12 patients out of 27 osseointegration failure patients and 9 out of the 30 control patients reported a dental history of acute pulpitis and the number was confirmed to evaluate the sensitivity of the NRS pain report.All the radiologic examinations from the 27 patients in which the dental implants failed to osseointegrate and the 30 patients from the control group were collected and evaluated by an independent experienced dental clinician by a blind design method to detect any suspected indication of osseointegration failure.t-test after checking the distribution of the data and p < 0.05 was defined as significantly different in this study.Data collected were analyzed by using SPSS20.0, and all the data were displayed with mean and 95% confidence intervals. Comparisons were performed and analyzed between the osseointegration failure group and the control group by the comparative Analyzing all the patients who received Dentium Superline implants delivered by the clinician involved in this study, 1426 Dentium Superline implants were delivered to 872 patients from Tianjin Medical University Second Hospital between Jan 2018 and Apr 2021, and 27 out of 1426 Dentium Superline implants failed to achieve osseointegration. The overall implant osseointegrated cumulative success rate is 98.1%.Among the 27 patients encountering dental implant osseointegrated failure, 13 of them were clinically accessed to be D1 bone density, 2 patients to be D2 bone density, 7 patients to be D3 bone density, and 5 patients to be D4 bone density. The results are shown in Based on the documentation of all 27 patients, the initial torque during placement of the Dentium Implants for the 27 patients was controlled between 20 N·cm to 60 N·cm with an average of 36.67 N·cm (95% CI: 32.2–41.2). This result showed no significant differences when compared with the control group 32.17 N·cm (95% CI: 30.35–36.65). The results are displayed in p=0.16). The average NRS number reported for severe pulpitis is 7.75 (95% CI: 7.14–8.36) from the osseointegration failure group and 7.78 (95% CI: 6.94–8.62) from the control group, and no significant differences were found (p=0.95).The average NRS number for blood taking from osseointegrated failure group was 2.12 (95% CI: 1.77–2.46) and the NRS reported from the control group is 2.45 (95% CI: 2.11–2.78), and there were no significant differences between the two groups  postsurgery pain reported by the 27 osseointegration failure patients were 5.42 (95% CI: 4.97–5.86), 5.35 (95% CI: 5.05–5.65), and 3.46 (95% CI: 3.02–3.91), respectively, which is significantly higher than those of the control group, which were 2.76 (95% CI: 2.37–3.15), 1.55 (95% CI: 1.07–2.03), and 0.483 (95% CI: 0.289–0.676). The results are displayed in 25 cases out of 27 dental implants osseointegration failure cases received the Dentium Superline implant with a two-stage submerged surgery and 2 out of 27 patients went through the one-stage nonsubmerged procedures. The results were displayed in 547 patients reported mild pain with no intervention with any pain control medication. 97 patients reported by phone follow-up, moderate to severe pain on the 1st day post surgery, 89 of them continued to report moderate to severe pain on the 3rd day post surgery phone follow-up, and 94 of them were administrated with NSAID (Motrin 600 mg Q6 h prn pain) or acetaminophen (650 mg Q6 h prn pain) after ruling out contraindications. All the 97 patients were scheduled for an additional appointment on the 14th day post surgery. 42 patients still complained of pain on the 7th day post surgery when removing suture or in clinic recall and 25 out of 42 patients encountered dental implant osseointegration failure. The other 2 patients who encountered osseointegration failure reported mild to moderate pain on the 1st and 3rd day but lasting no longer than 5 days. The odds ratio of poor osseointegration between the longer than 72 hours moderate to severe pain patients and no pain or mild pain patients was 153. The results are displayed in The local swelling was followed up on the 1st and 3rd day post surgery by phone and examined by the clinician on the 7-day follow-up. 617 out of 872 patients reported swelling and the swelling peak occurred on the 3rd day postoperative follow-up. 150 out of the 617 patients reported long-duration swelling on the 7th day post surgery following up and all of them were scheduled to have an additional follow-up on the 14th day post surgery. Unfortunately, among the 150 patients, 19 were found encountering poor osseointegration 1 or 2 weeks later. The odd ratio of poor osseointegration between longer than 7 days swelling patients and none or mild swelling patients is 12.94. The results are shown in th-day postsurgical appointment, 16 out of 26 patients (osseointegration failure group) were radiology suspected for poor osseointegration. One panoramic from one osseointegration failure patient and one panoramic from a successfully osseointegrated patient typically displayed the misleading information acquired from the radiology examination in Figures 3 out of 27 (osseointegration failure group) and 3 of 30 (control group) were suspected by the independent dental clinician when reviewing the 7th-day postsurgery X-ray. On the 14All the abbreviations used in this study are collected and displayed in Failing to achieve osseointegration tends to be very challenging for dental implant treatment as there are very limited interventions that can be implemented to combat this process .The overall osseointegration failure rate in the current study was 1.83%, which is consistent with the reports of relevant literature . DespiteMethods aiming to lower the risk of poor osseointegration encountering have been widely studied and reported by manufacturers and dental clinicians. In general, the methods include surface modification , design There are several clinical decisions including preventing surface contamination and postsurgical management to be taken into account when managing dental implant treatment . DetectiBased on the NRS data from the current study, moderate to severe postsurgery pain lasting for more than 72 hours could be an early indicator of the early lack of implant osseointegration. Attempting to address the causal association between long-lasting moderate to severe postsurgical pain and poor dental osseointegration, one of the hypotheses discussed in our group was that the inflammatory secretions elevate the tension of the periosteum and simulate the free nerve endings continuously and this hypothesis is consistent with the study reported by Aysan Shahnaz et al. . AdditioThe dental clinician from the current study reported no preference to take one-stage or two-stage surgery for the patients, except for bone graft cases or failing to match an ideal healing cap for the patients. However, as bone grafts were carried out for 5 of the osseointegration failure cases and 49 cases of the successful osseointegrated patients, the influences from the bone grafts were not independently analyzed in the current study. As the bone graft cases were all carried by a two stages submerged surgery, the selection bias from the current study may not be ideally minimized. The surgical size, site, and flap management may influence the pain severity reported by the patients; however, in more than 10 cases of all-on-six procedures, the postsurgery pain will be dramatically relieved within 48 hours post surgery in the current study. The blood test NRS reported by patients from the osseointegration failure group and control group was evaluated to minimize the reporting bias in the current study. The acute pulpitis NRS data was utilized to test the sensitivity of NRS in the current study and based on the result, all the patients displayed reliable reporting tendencies. One issue that should be taken into account is post-dental treatment pain could be TMJ-related. Based on this point of view, this part of bias could not be totally ruled out in this study as the pain reported by the patient could be of TMD origin rather than the implant surgery origin .Titration of postimplant pain control medication explored in Tianjin Medical University Second Hospital before the current study was carried out, and some cases of moderate to severe pain were reported occasionally. Patients who received dental implants would be routinely prescribed NSAID or acetaminophen post surgery when ruling out all the contraindications, which is consistent with the current protocol . In the In the current study, the D1 bone density displayed a higher odd ratio of osseointegration failure. Based on the documentation of the patients in the current study, additional osteotomy efforts would always be made to load the implant into the ideal depth. This may be concerning as the more time and effort the osteotomy takes, the more thermal trauma might potentially impact the bone . In addiThe radiological examination acts as a vital technique in making a dental diagnosis, treatment plan, or following up . In the Dental implant-related pain has been reported frequently and many dental clinicians are paying attention to this new aspect. Pain encountering could be reported at any stage during the implant treatment, including post implant installation and post prosthetic procedure. Many innovative techniques including telescopic dentistry utilized in the prosthetic procedure for the patients are available, making the prosthetic procedure more predictable . HoweverMore well-designed random control trial studies are needed to confirm the causal relationship between severe pain and osseointegration failure and future studies would also be needed to explore the physiological mechanism of the outcome in this study.Moderate to severe pain post dental implant surgery lasting more than 72 hours displayed a higher odds ratio of osseointegration failure. The radiographic examination failed to offer any predictable information on the early detection of poor implant osseointegration in this study. As a case-control study, we are looking forward to seeing more well-designed random controlled trial studies to be carried out to confirm the casual relationship between postsurgical pain and implant osseointegration failure. Also, the mechanism of the outcome of the current study needs more evidence to explain.


To evaluate the effect of duloxetine when added to a multimodal analgesia regimen on posthemorrhoidectomy pain, opioid consumption, and side effects.Prospective, randomized, double-blind placebo-controlled trial. This study included 62 patients who underwent hemorrhoidectomy. The patients were randomly assigned to receive oral duloxetine 60 mg or placebo 2 h before and 24 h after surgery. The primary outcomes were pain intensity - measured on an 11-point visual analog pain scale - and cumulative morphine consumption at 12, 24, and 48 postoperative hours.p = 0.68 at 12 h, 3.0; 2.0 – 5.0 vs. 3.0; 2.0 – 5.0, p = 0.56 at 24 h, and 2.5; 1.75 – 3.75 vs. 1.5; 0.5 – 3, p = 0.08 at 48 h. Further, cumulative morphine consumption did not differ between the duloxetine and placebo groups: 4; 1.25 – 10.75 mg vs. 7; 1.0 – 12.0 mg, p = 0.68 at 12 h, 9.5; 2.0 – 17.5 mg vs. 8.0; 4.0 – 18.0 mg; p = 0.80 at 24 h, and 11.0; 2.0 – 27.0 mg vs. 10; 4.0 – 24.0 mg, p = 0.78 at 48 h. Side effects did not differ between the groups.Fifty-two patients completed the study (25 in the duloxetine group and 27 in the placebo group). Pain scores did not differ between duloxetine and placebo: 4.5; 3.0 – 7.0 vs. 5.0; 3.5 – 7.0, Compared with placebo, duloxetine did not decrease pain intensity or morphine consumption during the first 48 h postoperatively.The study was retrospectively registered on the Brazilian Clinical Trials Registry . Substantial progress in understanding acute pain mechanisms has been made in the last few decades. The neurotransmitters involved in primary afferent stimulation and the role of the spinal grey matter in amplifying and perpetuating acute pain are now better understood .Consonant with the developing body of knowledge about pain mechanisms, multimodal analgesia is currently adopted for managing acute pain. Multimodal analgesia consists of using drug combinations to increase the analgesic effects and minimize the risks of adverse effects of the individual drugs. Currently, the most widely used multimodal analgesia approach for preventing posthemorrhoidectomy pain consists of the combined administration of opioids, non-steroidal anti-inflammatory drugs, local anesthetic infiltration, neuraxial anesthesia, and small doses of ketamine –4.Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor used to treat depression, anxiety disorders, diabetic neuropathy, and fibromyalgia. Both serotonin and norepinephrine play meaningful roles as neurotransmitters in the descending inhibitory pain pathways. Duloxetine has been found to inhibit central pain by potentiating serotonergic and noradrenergic inhibitory pathways , 6. SeveThe effects of duloxetine added to a multimodal analgesia regimen to decrease posthemorrhoidectomy pain are unclear. We hypothesized that, in patients undergoing hemorrhoidectomy, oral administration of duloxetine at a dose of 60 mg, 2 h before and 24 h after surgery could decrease the intensity of pain in the first 48 h of the PO period, compared to placebo.ensaiosclinicos.gov.br, identifier: RBR-9pdgms, registration date: 08/10/2020); the manuscript was written according to the 2010 Consolidated Standards of Reporting Trials (CONSORT) [This prospective, randomized, placebo-controlled, double-blind, parallel clinical trial was performed at the University Hospital of the Federal University of Santa Catarina, in Florianopolis, Brazil, from April 2019 through November 2020 after obtaining approval from the institutional review board (identifier: 2.722.942). Written informed consent was obtained from the participants. The study protocol was registered on the Brazilian Clinical Trials Registry , scheduled for elective hemorrhoidectomy under subarachnoid anesthesia. The exclusion criteria are listed in Table www.randomizer.org website.Block randomization was performed before participant recruitment was conducted by an investigator not involved in any other study phase. Sixty cases were randomized in blocks of 6 (3:3) and allocated to the study groups (duloxetine or placebo) using random numbers generated using the Identical capsules containing a placebo (500 mg of corn starch) or duloxetine  60 mg were prepared by the hospital pharmacy to ensure blinding of the participants, surgeon, anesthetist, and data collectors. Capsules were packed in opaque, sealed envelopes and sequentially numbered according to the randomization list provided by the hospital pharmacy. Envelopes were provided to the ward nurse after patient admission to the hospital and were opened at the study drug administration, assuring that neither the nurse administrating nor the patient receiving the capsule could presume the group assignment.The primary study outcomes were postoperative pain intensity and patient-controlled analgesia (PCA) morphine consumption. Pain intensity was assessed on an 11-point visual analog scale (VAS), where zero meant no pain and ten meant the worst pain imaginable. Pain scores were assessed at the patient’s arrival to the post-anesthesia care unit (PACU) (time 0), and after 12, 24, and 48 PO hours. Additionally, patients were instructed to assess the pain at first PO defecation on the same VAS.The cumulative morphine consumption was extracted from the PCA pump  at the 12th, 24th, and 48th PO hours. Secondary outcomes were the frequency of adverse events attributable to duloxetine , recorded by ward nurses and investigators during the initial 48 PO hours, and the time to the first defecation.− 1 and fentanyl 1 μg.kg− 1 upon arrival to the operating room (OR), Cefoxitin 2 g was administered for perioperative antibiotic prophylaxis. Surgical anesthesia was provided with a spinal block with 10 mg of 0.5% hyperbaric bupivacaine. Ketoprofen 100 mg, dipyrone 2 g, and ondansetron 4 mg were administered at the end of surgery for preventive analgesia and postoperative nausea or vomiting prophylaxis.Patients were admitted to the hospital the evening before surgery. Instructions on how to use the visual analog pain scale and the PCA pump were provided during the preoperative visit. No bowel preparation was performed. The study drug was administered orally 2 h before surgery and 24 h after the procedure by the nursing staff. Patients were premedicated with intravenous (i.v.) midazolam 0.03 mg.kgThe patients underwent closed hemorrhoidectomy in the jackknife position using a diathermal scalpel for resecting the three hemorrhoidal piles. After the procedure, the patients were transferred to the PACU.− 1, 50 mL; b) no background infusion; c) bolus demand: 1 mg; d) lock-out time: 5 min; e) maximum dose in 1 h: 8 mg.Postoperative analgesia consisted of ketoprofen 100 mg at 12-hour intervals and dipyrone 2 g at six-hour intervals during the first 48 PO hours. Nausea and vomiting were treated with i.v. ondansetron 4 mg. Additionally, all patients used the i.v. PCA pump during the first 48 h after surgery using the following protocol: a) solution: morphine sulfate 1 mg.mlPatients were discharged 48 h after surgery. Dipyrone 500 mg q.i.d. for 7 days, nimesulide 100 mg b.i.d. for 6 days, and tramadol 100 mg, for rescue analgesia were prescribed orally. A PO follow-up visit was scheduled for the eighth PO day. Patients were also instructed to return to the hospital in case of intractable pain, bleed, nausea or vomiting, urinary retention, or any other condition.2) or Fisher exact tests. Mann-Whitney U tests were used to compare pain scores and cumulative morphine consumption between the groups at each measurement time point.The variables included in the analyses were age, sex, body mass index, ASA classification, tobacco use, HD degree, preoperative symptoms, duration of surgery, OR time, VAS pain scores, cumulative amount of morphine during the initial 48 PO hours, time to first defecation, and side effects. The distribution of continuous variables was assessed using the Kolmogorov-Smirnov, Shapiro-Wilk, and Lilliefors tests. Normally distributed continuous variables were compared between the groups using unpaired Student’s t-tests. The associations between categorical variables and treatments were assessed using the chi-square test . Sample size calculations were performed using the G*Power software . ProbabiSixty-two patients were assessed for study eligibility between April 2019 and November 2020. Seven patients did not meet the criteria for inclusion in the study, and hence 55 patients were initially selected. Three patients were excluded during the study. Fifty-two patients, 27 in the placebo group and 25 in the duloxetine group, completed the study  were lost due to technical reasons. Consequently, the analysis of morphine consumption was based on 16 patients from the duloxetine group and 19 patients from the placebo group, with no between-group difference Table .Table 4Ip = 0.87). The prevalence of side effects attributable to duloxetine did not differ between groups . Median VAS pain scores at the first defecation were 10 (25th - 75th percentiles = 9 – 10) in the duloxetine group, and 10 (25th - 75th percentiles = 8 – 10) in the placebo group (This study addressed the effect of duloxetine (60 mg) administered 2 h before and 24 h after surgery on posthemorrhoidectomy pain, morphine consumption, and side effects compared to placebo. The main findings were that duloxetine did not affect postoperative pain intensity or morphine consumption. Also, the incidence of side effects attributable to duloxetine was similar between the duloxetine and placebo groups.Several studies that evaluated the postoperative analgesic effect of duloxetine have shown a significant effect , 18–21, Such contrasting results may result from methodological differences among the studies, including the type of anesthesia, type and extent of surgery, patient characteristics, surgical pain intensity, and the quality of background analgesia. Low-to-moderate VAS pain scores were found among patients in the placebo group of this study, further suggesting that adequate background analgesia provided to all patients may have blurred any existing analgesic effects of duloxetine. Although this may be an attractive explanation, in other studies in which low-to-moderate pain was reported in the placebo control groups, duloxetine has been associated with either significant or non-significant analgesic effects , 24. TheSome methodological issues may limit the generalizability of our findings. First, results were based on postoperative opioid consumption and visual analog pain scores, imperfect surrogates for postoperative pain intensity. Both are affected by factors dependent on individual patients  . Second,The current study should only be interpreted within the context of its limitations. This trial included patients with ASA physical status classes I and II aged 18 through 65 years submitted to closed hemorrhoidectomy; therefore, our findings should not be generalized to patients undergoing different surgical procedures or with other demographic features. Because the residual effect of bupivacaine spinal anesthesia may last up to 7 h in the sacral roots responsible for conducting anal pain , VAS scoIn conclusion, duloxetine in doses of 60 mg administered orally 2 h before and 24 h after surgery to patients undergoing hemorrhoidectomy does not decrease pain intensity or morphine consumption during the first 48 PO hours, compared to placebo. Similarly, pain at first defecation is not affected by duloxetine, and the prevalence of side effects was similar between the duloxetine and placebo groups. We highlight that this is a small pilot study using a heavy postoperative background analgesic regimen that may have obscured any analgesic effect of duloxetine. Another study from our group using the same background analgesic regimen did not provide evidence for any substantive analgesic effect of duloxetine . Also, t


However, there was no difference in estimated muscle mass. Shorter duration of pain, opioid usage, pain in lower limbs, sleep disturbance, and lower handgrip strength were significantly associated with neuropathic-like pain symptoms. In patients with handgrip strength below the reference values by sex, experiencing radiating pain and at least moderate sensory symptoms by light touch and thermal stimulation were more frequently reported. In conclusion, lower handgrip strength appeared to be an independent factor associated with symptoms suggestive of neuropathic pain in this population. Interventional studies are required to determine whether improvement in muscle strength can reduce the neuropathic pain component in chronic musculoskeletal pain.The relationship between sarcopenia and pain remains unclear; thus, this study evaluated whether muscle strength is independently associated with neuropathic-like pain symptoms in patients with chronic musculoskeletal pain. A cut-off score of painDETECT ≥13 was used to indicate a possible neuropathic component. Handgrip strength was measured, and muscle mass was estimated. A total of 2599 patients, including 439 patients who reported neuropathic-like pain symptoms (16.9%), were included for analysis. Handgrip strength was significantly lower in patients experiencing neuropathic-like pain symptoms (23.23 ± 10.57 vs. 24.82 ± 10.43 kg,  Sarcopenia is a geriatric syndrome characterized by a decrease in muscle mass, muscle strength, and physical performance. According to a recent systematic review and meta-analysis, the prevalence of sarcopenia ranged from 10 to 27%, although there were differences according to classification criteria or cut-off values. Untreated sarcopenia causes functional degradation and disability, impacts quality of life, and requires increased costs of care ,4. HandgAmong patients with chronic pain, a fifth of patients appear to experience neuropathic pain symptoms which are potentially caused by a lesion or disease affecting the somatosensory nervous system ,10. The The causal relationship between sarcopenia and pain remains unclear, but patients with pain appeared at a higher risk of sarcopenia than those without pain . The feaTherefore, the goal of this study was to explore the association between HGS and neuropathic-like pain symptoms based on painDETECT results in patients with chronic musculoskeletal pain. In addition, the factors associated with neuropathic-like pain symptoms in this population were investigated, and differences in the characteristics of pain symptoms according to HGS, based on the results of each painDETECT item, were examined.Approval from the Institutional Review Board was obtained and in keeping with the policies for a retrospective review, informed consent was not required (No. 4-2022-0168). A total of 3712 adult patients aged 20 to 98 who underwent treatment for their pain at the pain clinic of a tertiary university hospital in 2017 were initially included in this study. Musculoskeletal pain was defined as pain in the following five anatomical areas: neck ; shoulder and upper limbs ; back (thoracic spine) and chest wall; lower back (lumbar spine); and hip and lower limbs . Chronicity was established by the persistence of pain beyond 3 months. Patients with incomplete medical records or who could not measure handgrip strength due to hand osteoarthritis or a neurological disorder were excluded. Additionally, patients with acute pain (<3 months) or who did not have musculoskeletal pain were excluded.Neuropathic-like symptoms were assessed by means of the patient-reported painDETECT questionnaire at the patient’s initial visit to our clinic. Patients freely described their pain symptoms and filled out the validated Korean version of the painDETECT questionnaire . The paiHGS was measured three times each on the left and right side using a Smedley-type handheld dynamometer  at the initial visit. HGS was measured and recorded by an independent tester. The patients were requested to sit in a comfortable position with their elbows extended and to squeeze the dynamometer with maximum strength . The higPatient characteristics including age, sex, body mass index (BMI), and pain-related variables were collected by electronic medical record chart review. Variables included diagnosed comorbidities that led to continued medical interventions with regular hospital visits, such as hypertension, diabetes mellitus, cardiovascular disease, mental health problems, and osteoporosis/osteopenia. Mental health problems were defined as cases experiencing psychiatric treatment or medication for depression, anxiety, or stress in the past year. The following factors were identified as pain related: duration of pain, average pain score on the numeric rating scale  in the last 4 weeks, current opioid usage for at least 1 month, primary pain locations according to anatomical area groupings, the presence of multiple pain sites, and sleep disturbance. The presence of multiple pain sites was defined as pain in at least two different anatomic body sites. Sleep disturbance was defined as any difficulty in the initiation of sleep and/or awakening midnight and use of sleep pills over the course of at least 3 months. t-test, chi-squared test, or Fisher’s exact test as appropriate. The Mann–Whitney U test was utilized for continuous variables with non-normal distributions. Significant univariate variables with a p-value threshold of 0.2 were included in multivariate logistic regression analyses to identify the factors associated with neuropathic-like symptoms based on a painDETECT score of ≥13 in patients with chronic musculoskeletal pain, and the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. For a sub-analysis, the study population was divided into two groups: a normal HGS group (≥28 kg for men and ≥18 kg for women) and a low HGS group (<28 kg for men and <18 kg for women), according to the Asian Working Group for Sarcopenia (AWGS) 2019 guideline [p-value < 0.05 was considered statistically significant. Data are expressed as mean ± standard deviation (SD) for continuous variables and number (percentages) for categorical variables. For ordinal data and discontinuous variables, we expressed the data as median and interquartile range (IQR). The normality of distribution was examined by the Shapiro–Wilk test to ensure proper statistical treatment. Demographics and clinical variables were analyzed by independent Overall, a total of 2599 patients aged 20 to 98 years, consisting of 439 patients with possible neuropathic pain components (painDETECT score ≥ 13) and 2160 patients unlikely to have neuropathic pain components (painDETECT score < 13), were finally analyzed in this study . p < 0.001). The mean pain score was significantly higher in patients with neuropathic-like pain symptoms than in those without neuropathic-like pain symptoms . In addition, the proportions of patients taking opioids and experiencing sleep disturbances were significantly higher in patients with neuropathic-like pain symptoms. The lower back area was the most common pain location regardless of the presence of neuropathic-like pain symptoms, and there was a significant difference in pain locations between the two groups. Patients with pain on back or chest wall and lower limbs reported higher painDETECT scores. Patients with pain on upper limbs or low back area showed lower HGS than those with other pain sites. The prevalence of multiple pain sites was comparable between the two groups. The sarcopenia-related data, ASM and SMI, were comparable between the two groups. However, HGS was significantly lower in patients with neuropathic-like pain symptoms .Patient demographics, pain-related clinical data, and sarcopenia-related data were compared between the two groups . Age, seThe sex-specific comparison showed that HGS was significantly lower in female patients with neuropathic pain components, but not in male patients. A significant difference was not observed in estimated muscle mass parameters, both ASM and SMI, between the two groups for both sexes .p < 0.001), opioid usage , pain in lower limbs , sleep disturbance , and lower HGS  were independent factors associated with neuropathic-like pain symptoms  and the low HGS group (n = 978), the proportion of patients experiencing moderate to severe sensory symptoms (score of 3 ≥ 5 on each question) resulting from either light touch or thermal stimulation was significantly higher in the low HGS group. In addition, there was less persistent pain with slight fluctuation, and a radiating pain pattern was more predominantly reported, in patients with low HGS. The total painDETECT score was significantly higher in patients with low HGS. Other characteristics of pain symptoms on painDETECT were similar between the two groups .Several demographic , psychosocial , clinical , and genetic factors have been reported to be associated with neuropathic pain . AdditioThe causal relationship between pain and sarcopenia has not been fully elucidated; however, a positive correlation between them was found in a recent meta-analysis based on results of 10 observational studies . CurrentIn the present study, female patients with neuropathic pain components interestingly exhibited lower HGS than those without with neuropathic pain components, but this was not observed in male patients. The overall prevalence of sarcopenia and chronic pain was higher in women compared to men ,24,38. SIn addition, our results showed that shorter pain duration was associated with neuropathic-like pain symptoms. In a previous study in which similar scores were observed among musculoskeletal pain patients with several months to years of pain duration, the painDETECT score was not associated with the time elapsed since pain onset . HoweverThere are several limitations in this study. There may be information bias due the retrospective nature of the current study. Additionally, this study was performed in a single-center institution with a sample involving a homogenous racial study population. This cross-sectional study could not determine a causal relationship between muscle strength and neuropathic pain; thus, a longitudinal study with a large population should be conducted. In this study, socioeconomic factors, which can affect pain and sarcopenic status, were not included. This study used a real-world clinical practice model; thus, most patients were already taking various types of analgesics or received some interventional pain procedures during the initial visit to our clinic. This potential confounder, especially exposure to gabapentinoids and antidepressants, could affect the painDETECT score. In this study, the detailed diagnoses of the study population based on pain etiologies could not analyzed due to some technical difficulties. Although ASM and SMI were estimated using the previously validated equation, this equation has not been validated in patients with chronic pain. Additionally, bioelectrical impedance analysis or dual-energy X-ray absorptiometry were not used in this study. Thus, low HGS alone did not fully satisfy the current diagnosis criteria for sarcopenia in the present results. Finally, we used a single self-reported questionnaire in this study; therefore, evidence of the association of muscle strength with neuropathic pain using neurophysiological tests may be warranted.This study demonstrated that lower HGS was an independent factor associated with neuropathic-like pain symptoms in patients with chronic musculoskeletal pain. This was predominantly observed in female patients, and patients with low HGS below the reference values by sex reported more sensory symptoms suggestive of allodynia and thermal hypersensitivity. Therefore, by performing HGS measurements for patients with chronic musculoskeletal pain, it is possible to expect the development of neuropathic-like pain symptoms and provide appropriate management to increase the probability of a positive outcome. Furthermore, interventional studies are required to determine whether improvement in muscle strength can reduce neuropathic pain components in chronic musculoskeletal pain.


Osteogenesis Imperfecta affects approximately 1 in every 10,000 people. Musculoskeletal disorders and pain are common in adults with Osteogenesis Imperfecta, but specific knowledge of the problems people have is lacking. Access to therapy services for adults with Osteogenesis Imperfecta is variable. We designed this analysis to better understand the musculoskeletal disorders and consequent therapy needs for adults with Osteogenesis Imperfecta. This study was a cross-sectional analysis of outpatients with Osteogenesis Imperfecta. Adults attending a newly established multidisciplinary clinic at a tertiary centre in 2019 were included. A highly specialist physiotherapist worked within the clinic to offer therapy input if required and to refer patients to appropriate therapy as needed. People over the age of 18 were included if they had a diagnosis of Osteogenesis Imperfecta. Data were collected over a five month period using routinely collected clinical information and patient reported outcomes.n = 19) of patients reported moderate to severe problems with mobility on the EQ-5D with over half reporting problems with self-care and ability to carry out usual activities. Over 50% of patients in clinic also reported anxiety (EQ-5D). During the consultation 70% of patients received therapy input which was either advice in clinic or an onward referral to the appropriate service. The referral rate to specialist out-patient rehabilitation services at a tertiary centre was 30%.Over five months 50 patients attended the clinic. Musculoskeletal pain was a significant feature reported by 84% of patients. Over 50% of patients reported persistent pain for longer than one year duration and the most common site of pain was in the spine (46%). No difference in pain between types of OI and age. Forty five per cent (This analysis highlights the high prevalence of MSK pain in adults with OI and the effect on physical function and emotional wellbeing. This study demonstrates the diverse needs of the adult Osteogenesis Imperfecta population and the need for suitable multidisciplinary therapy services. Osteogenesis imperfecta (OI) comprises a heterogeneous group of genetic disorders characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures with variable severity. OI affects approximately 1 in every 10,000 people .The clinical presentation of OI varies widely and is classified accordingly; mild (type I), neonatally fatal (type II), moderate deformity (type IV) and severe progressive skeletal deformity (type III) . OI can Management of OI should be multidisciplinary involving experienced medical, orthopaedic, physiotherapy and rehabilitation specialists. There is currently no cure for OI, although bisphosphonate therapy is used in children and can be used in adults . The mulIn October 2019 a multidisciplinary team (MDT) clinic was established at a tertiary centre, for adults with OI. The team included two consultant metabolic bone specialists, a clinical nurse specialist, a geneticist, a research co-ordinator and a specialist physiotherapist with expertise in hypermobility and persistent pain. The project was reviewed by the local research and innovation centre at The Royal National Orthopaedic Hospital SE19.0035 and considered a service evaluation therefore no formal ethical approval was required. Routine clinic data was captured as part of the clinic appointment therefore verbal consent was obtained and recorded as part of patient notes. This was considered appropriate under the guidance of the research innovation centre.The type of OI presentation was categorised by the consultants in clinic according to the Sillence classification  and whetSTROBE standards for use in observational studies were used.Routine data was collected in the MDT clinic for patients who were over the age of 18 years and had a clinical diagnosis of OI.Data were collected over a five month period from October 2019 to February 2020 by the physiotherapist in clinic. Demographic data including age, gender and work status were collected. Patient reported outcome measures EQ-5D-5L (EuroQol)  and brieDescriptive data are given as means, ranges, frequencies and percentages. Excel version 14.7.3. was used to make calculations. Further statistical analysis was performed using Stata version 15.1. The comparison between the types of OI was performed using an un-paired t-test and the EQ-5D-5L outcomes were compared between groups using the Mann–Whitney test. An additional analysis examined the association between age and BPI pain score using a Pearson correlation.During the five month data collection period fifty adults with OI attended the MDT clinic. The demographic data is presented in Table n = 43) of those attending reporting symptoms of pain. For those patients reporting pain, the duration of pain symptoms ranged from 0–12 months for (n = 14) of patients, between 1–2 years for (n = 12) of patients and (n = 17) of those in clinic reported having pain for over 2 years. The patients reported sites of pain in different areas of the body with (n = 14) reporting 1 site of pain, (n = 11) described 2 sites of pain and (n = 18) reporting 3 or more sites of pain. The distribution and frequency of the site of pain is shown in Fig. MSK pain was a significant feature of patients presenting in clinic with 86% (n = 18) of patients have mild symptoms with a pain score of 3 or less, 35% (n = 13) have a pain score of 4–6 which was classified as moderate and 16% (n = 6) fell into the severe category with pain over 7/10. Overall 29% (n = 11) of patients had an average interference score of > 5 inferring that it impacted on their general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. Statistical analysis demonstrated no difference in age (p = 0.82) or BPI pain scores (p = 0.20) when comparing the patients with OI type I and OI type IV. See Table The BPI severity scale was fully completed by 37 patients. This showed that 45% (n = 42)represents the data collected. In clinic 22% patients used a wheelchair as their primary mode of mobility, this included a self-propelling and powered wheelchairs, 18% of patients used a walking stick or crutches and 60% mobilised unaided. The mobility measure demonstrates that 45% (n = 19) of adults presenting in clinic have moderate-severe problems with their mobility and 14% (n = 6) reported they were unable to mobilise or had severe problems with mobility and 16% (n = 6) of patients reported no problems with their mobility.The EuroQol EQ-5D-5L was used to measure overall quality of life. There were 42 full sets of data collected. One person declined to complete it, one was not collected and six were incomplete. Figure n = 11) of patients and 33% (n = 14) reported moderate pain problems. Severe or extreme pain was reported by 28% (n = 12) of patients.Of the patients who completed the EuroQoL EQ-5D-5L reported pain 37/42 (88%). Slight pain problems were reported by 26% (n = 22), 16% (n = 7) of patients reporting extreme to severe problems. However, 40% (n = 17) had no difficulties with self-care.Of the completed measure just over half of the patients reported problems with managing self-care  had moderate problems carrying out their usual activities whilst 23% (n = 10) had severe or extreme/unable to carry out usual activities and 33% (n = 14) did not report any difficulties with usual activities. Overall 54% (n = 23) reported anxiety. Of those patients, 24% (n = 10) reported slight problems, 14% (n = 6) reported moderate problems and one patient reported severe problems.Regarding usual activities the data shows that 23% (P = 0.01). The scores were higher for type 4 patients. 80% of type IV patients scored 4 or 5 on this scale, compared to only 15% of type I patients. See Table The EQ-5D-5L analysis suggest a statistically significant difference in mobility score between type I and IV patients (P = 0.08). None of the other EQ-5D-5L scores varied significantly between the two groups. See Table There was also some evidence that type IV patients had higher EQ-5D-5L self-care scores, although the difference for this measure did not reach statistical significance (n = 10) of patients in clinic, all of which were classified with Type I OI. A further 30% (n = 15) of patients were referred to out-patient rehabilitation services at a tertiary centre. A single patient with Type IV OI was referred to a bespoke rehabilitation in-patient stay at the same centre and a further 12% (n = 6) of patients were referred to their local community therapy service. One patient required a social services referral and 4% (n = 2) consented to onward referral for mental health services. The physiotherapist in clinic liaised with a local therapy team on behalf of one patient.During the consultations, 70% of patients received therapy input which was either advice in clinic or an onward referral, Fig. The data collected from the multidisciplinary clinic demonstrates the high prevalence of MSK pain in adults with OI and the consequent effect on daily function. MSK pain at numerous joints in the body is a key feature reported by this adult population and the results demonstrate that there was no correlation between the type of OI, age and the pain reported. Over half of patients in clinic reported persistent pain according to the International Association for the Study of Pain (ISAP) definition  A healthIt is widely understood that persistent pain adversely affects daily activities, physical and psychological health . In a stThe most prevalent site of pain was the spine which may be explained by a high prevalence of spinal deformity such as scoliosis or vertebral fractures in the OI population . Weight An interesting finding was just over half of patients reported anxiety symptoms on the EQ-5D-5L demonstrating that adults with OI may also suffer with mental health conditions. A systematic review by Tsimicalis et al. 2016  supportsThe physiotherapist in clinic was able to provide advice within the clinic setting for 20% of patients. Within the clinic the physiotherapist was able to make an onward referral to the most relevant service based on the assessment, including psychology, occupational therapy, social services, physiotherapy or bespoke rehabilitation at a tertiary centre. Managing MSK disorders and long-term conditions holistically, has been advocated to reduce the impact of an individual’s disability and maximise their quality of life . This crThis was a single centre study and data collection was curtailed as the clinic was suspended in March 2020 due to the Covid-19 pandemic. Due to this there was not enough data on type III OI patients to support statistical comparisons. Furthermore, incomplete data for outcome measures may have limited the results, this could be overcome if they were digital for any future studies in this area. We did not record the reasons or diagnosis of MSK pain as this was beyond the remit of this analysis but would be an interesting further study.This study highlights the high prevalence of MSK pain in adults with OI and the effect it has on their physical function and emotional wellbeing. The diverse needs of the adult OI population are demonstrated in terms of the wide variety of onward referrals required. Further work is required to understand the experiences of people with OI in accessing therapy services and their perceived therapy needs to support service design.