The objective of this study was to examine the impact of around-the-clock (ATC) administration of intravenous (IV) acetaminophen following robot-assisted radical prostatectomy (RARP). Intravenous infusion of acetaminophen was started on the day of the operation at 1000 mg/dose every 6 h, and the infusion was continued on a fixed schedule until postoperative day 2 a.m. In a retrospective observational study, we compared 127 patients who were administered IV acetaminophen on a fixed schedule (ATC group) with 485 patients who were administered analgesic drugs only as needed (PRN group). We investigated postoperative pain intensity and additional analgesic consumption on postoperative day 0, 1, 2, 3, and 5 between the two groups. Postoperative pain scores were significantly lower in the ATC group than in the PRN group at 1 and 2 days, and this period matched the duration of ATC administration of IV acetaminophen. Postoperative frequency of rescue analgesia was significantly lower in the ATC group than in the PRN group at postoperative 0, 1, and 2 days. ATC administration of IV acetaminophen has the potential to be a very versatile and valuable additional dose to achieve appropriate postoperative analgesia in patients with RARP. Although the incision size is small, visceral irritation and prolonged pneumoperitoneum due to high pressure can increase postoperative pain after RARP2. In addition, insertion of a urethral catheter is thought to be mandatory for several days after radical prostatectomy, but penile pain and bladder spasms associated with the urethral catheter become issues in postoperative pain management3. Despite how common the procedure has become, there is little objective data on postoperative pain and convalescence after RARP.Robot-assisted radical prostatectomy (RARP) is known to cause less postoperative pain than open surgery. However, during the period immediately after surgery, patients have reported experiencing moderate to severe pain following RARP4. A randomized clinical trial (RCT) evaluated the efficacy of around-the-clock (ATC) administration of analgesics in patients after RARP5. This RCT showed that there was no difference in pain score or opioid use between patients receiving intravenous (IV) acetaminophen and IV placebo in the perioperative setting of RARP.These characteristics of pain after RARP suggest that a scheduled dosing regimen may be effective. However, many clinicians fear that regular scheduled administration of analgesics may result in unnecessary and/or excessive administration of analgesics, resulting in undesirable and potentially harmful side effects5.Acetaminophen is a widely accepted standard treatment option for mild acute postoperative pain. IV acetaminophen is currently approved by the Food and Drug Administration (FDA) for analgesic indications. It is a fast and effective drug with fewer side effects compared with non-steroidal anti-inflammatory drug (NSAID) which cause gastrointestinal bleeding and renal insufficiency. These drug properties of acetaminophen are suitable for pain control in patients following RARP, which is common procedure on elderly patients. Surprisingly, the use of IV acetaminophen has not been studied in patients following radical prostatectomy; no outcomes are currently availableDue to the lack of studies on the effectiveness of ATC administration of analgesics for the postoperative pain management in patients following RARP, additional study is needed. We hypothesized that patients who received regularly scheduled IV acetaminophen after RARP would report less pain than those who received analgesics as needed . The purpose of this study was thus to determine whether ATC administration of IV acetaminophen increased or decreased pain intensity and increased or decreased frequency of rescue analgesia in patients who underwent RARP compared with PRN administration. In addition, we evaluated the effect of ATC administration on the severity of catheter related bladder discomfort (CRBD).A total of 783 patients with localized PCa who had undergone RARP at Hiroshima University Hospital between May 2010 and April 2020 were included in this study. Exclusion criteria included chronic opioid use, liver disease, allergy to acetaminophen, baseline dementia, chronic diathesis, and chronic kidney disease. We excluded 62 patients who had pain control with patient-controlled epidural analgesia (PCEA), 15 patients who underwent Retzius sparing RARP, 68 patients who were treated with Androgen deprivation therapy (ADT) before RARP, and 26 patients who had chronic kidney disease (CKD). Opioid analgesics were not used in all patients for postoperative pain control following RARP in this cohort. A new postsurgical analgesia protocol (ATC administration) has been applied to all patients following RARP since December 2017. We compared 127 patients who underwent ATC administration of IV acetaminophen (ATC group) with 485 patients under PRN (PRN group). This is a retrospective observational study. After obtaining the approval of institutional review board of Hiroshima University Hospital, the medical records of all patients with PRN group (between May 2010 and December 2017) and patients with ATC group (between December 2017 and April 2020) were retrospectively reviewed  and 6–10 mg/kg of rocuronium, and was maintained with propofol at 1.0–3.5 µg/ml of TCI, sevoflurane at 1.0–2.0% or desflurane at 3–5% in combination with remifentanil at 0.05–0.5 µg/kg/min. Doses of the anesthetics were determined with reference to the electroencephalogram monitor Entropy . Fentanyl, acetaminophen (1000 mg or 15 mg/kg), and flurbiprofen (50 mg) were administered in the operating room at the discretion of the anesthesiologist.In the ATC group, IV infusion of acetaminophen  was started every 6 h on the day of the operation at 1000 mg/dose for patients weighing ≥ 50 kg or 15 mg per kg of the body weight for patients weighing < 50 kg. These administrations continued on a fixed schedule until postoperative day 2 a.m. after the start of oral intake and oral medications. In the case of PRN administration of analgesics, all patients received on-demand analgesic drugs, such as diclofenac sodium suppository (50 mg) or IV flurbiprofen axetil (50 mg) on fasting and loxoprofen sodium (60 mg) or Celecoxib (200 mg) after the start of oral intake and oral medication. Narcotics were not routinely prescribed in our protocol of pain management.The primary endpoint was postoperative pain intensity measured on a numeric rating scale (NRS) that ranged from 0 = “no pain” to 10 = “unbearable pain” on days 0, 1, 2, 3, and 5 postoperatively. Pain scores were recorded at scheduled times until discharge. Postoperative pain level was measured on the NRS by a nurse once every 8 h during routine measurements of vital signs. Postoperative pain intensity and additional analgesic consumption (number of doses) were compared between the two groups on days 0, 1, 2, 3, and 5 postoperatively. The CRBD score was rated on a 4-point scale and defined as follows: 0 = no discomfort, 1 = mild discomfort, 2 = moderate discomfort, 3 = severe discomfort. CRBD score was measured by a nurse in the morning on postoperative day 0, 1, 2, 3, and 5 until removal of the urethral catheter.p value of < 0.05 was determined to be statistically significant. All values reported are means ± standard deviation, and the survey data were analysed using an unpaired t-test. They were also analysed using JMP 15 software .The baseline patient characteristics and surgical outcomes were examined using a chi-squared test, Mann–Whitney U test, and one-way analysis of variance (ANOVA) analysis. In all tests, a All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Institutional Review Board (IRB) of Hiroshima University Hospital approved this research protocol (IRB No. 3786).This was a retrospective observational study, and the requirement for written informed consent was waived by the IRB. The research content was posted on outpatient of Hiroshima University Hospital after approval and data of cases without opt-out intention were adopted.p = 0.015). There were no significant differences between the ATC and PRN groups in the mean preoperative eGFR value. The rate of pelvic lymph node dissection was significantly higher in the ATC group than in the PRN group , and operation time was significantly longer in the ATC group than in the PRN group . In the distribution of the D’Amico risk group classification, the ratio of high risk was significantly higher in the ATC than in the PRN group . There was a significant difference between groups in analgesics at the end of anesthesia; however, there was no significant difference in intraoperative dose of Fentanyl. In the evaluation of postoperative outcomes, there were no significant differences between groups in time to ambulation, oral intake, and length of stay.Table p = 0.001) and 2  days, and this period matched the duration of ATC administration of IV acetaminophen  data were collected from 612 patients, among whom 127 patients (21%) were in the ATC group. Postoperative pain scores were significantly lower in the ATC group than in the PRN group at postoperative 1 , 1 , 2  days, and this period matched the period of ATC administration of IV acetaminophen  days. There were no significant differences between groups at postoperative 1 , 2 , 3 , and 5  days  were significantly lower in the ATC group than in the PRN group at postoperative 0  during the postoperative period in patients who have underwent surgical procedures, especially urinary intervention. CRBD symptoms associated with indwelling urinary catheters are similar to those of overactive bladder, including suprapubic discomfort, urinary urgency, pollakiuria, and a burning sensation3.We feel this information is valuable in counseling patients about their treatment options after diagnosis of localized prostate cancer, because the anxiety of potential pain associated with surgery is certainly a factor that weighs into a patient’s decision-making process. We think this study will give physicians an objective tool in counseling patients who are considering undergoing RARP but have reasonable concerns about what they may expect during their periods of convalescence. This information should be useful in counseling patients on the merits of RARP relative to other less invasive therapies for prostate cancerThere were some limitations in our study. First, this is a single center study of only the Japanese population, so it may not be applicable to other populations. We recommend more large-scale, well-designed RCTs on patients following RARP to improve confidence in our conclusions. Second, we investigated postoperative frequency of rescue analgesia for the evaluation of ATC administration. The rescue analgesics were different in our protocol, so we should improve the study protocol for a more accurate evaluation. Third, we did not evaluate side effects such as liver disfunction. Many drugs including analgesics were used during the perioperative period, and it was unclear whether any of the side effects were particular to acetaminophen. Therefore, we did not investigate complications in this study population.In summary, the results of this study suggest the effectiveness of ATC dosing of acetaminophen during early postoperative recovery of patients following RARP, particularly in the first 2 days. Further research may be needed to determine if ATC administration benefits other populations following urologic surgery.ATC administration of IV acetaminophen has the potential to be a very versatile and valuable additional dose to achieve appropriate postoperative analgesia in patients with RARP. We feel this information will be valuable in counseling patients about their treatment options after diagnosis of localized prostate cancer, because the anxiety of potential pain associated with surgery is certainly a factor that weighs into a patient’s decision-making process.


Disability was moderately correlated with the number of latent MTrPs in the tensor fasciae latae muscle . Conclusions: This secondary analysis found that the prevalence of the MTrPs varied from 11% to 50% in different muscles of patients with mild to moderate painful knee osteoarthritis. Pain was correlated poorly with the prevalence of latent and active MTrPs in the hamstring muscles, and disability correlated moderately with the number of latent MTrPs in tensor fasciae latae.Objective: To determine the prevalence of myofascial trigger points (MTrPs) and the correlation between the number of MTrPs and pain and function in patients presenting knee pain osteoarthritis (OA). Methods: This was a secondary analysis of data from a cross-sectional study. The prevalence of MTrPs located in tensor fasciae latae, hip adductors, hamstrings, quadriceps, gastrocnemius, and popliteus muscles was studied in 114 patients (71 men and 43 women) with knee OA. Pain and functionality were assessed with a numerical pain rating scale (NPRS), the Western Ontario, McMaster Universities Osteoarthritis Index (WOMAC) score, the Barthel Index, and the timed up and go test. Results: The prevalence of latent MTrPs was detected via palpation and was estimated to be 50%, 35%, 25%, 29%, 33%, and 12% for tensor fasciae latae, hip adductors, hamstrings, quadriceps, gastrocnemius, and popliteus muscles, respectively. The prevalence of active MTrPs was estimated to be 11%, 17%, 30%, 18%, 25%, and 17% for tensor fasciae latae, hip adductors, hamstrings, quadriceps, gastrocnemius, and popliteus muscles, respectively. Pain was measured with the NPRS scale and was poorly correlated with the prevalence of latent MTrPs (r = 0.2;  In Europe osteoarthritis (OA) is the most common form of chronic pain 34%) reported, and has a high economic and social burden on society . This bu4% reportPain-osteoarthritis (pain-OA) has traditionally been viewed as peripherally mediated nociceptive pain . Many peThe presence of MTrPs in muscles near the knee is often ignored during the clinical diagnosis, which may be a primary or secondary cause of another diagnosis . The newImprovements in world health care have led patients to focus their attention on prevention, seeking care for pain and the correct management to slow down the progression of OA. Identifying the factors that lead to pain is fundamental for improving the management of knee OA symptoms, and preventing the onset of permanent or chronic pain . In thisWe performed a secondary analysis of data from a cross-sectional study. The previous study aimed at describing and comparing demographic, clinical, and myofascial pain syndrome characteristics in patients with knee OA by sex and age distribution. The methods and description of the trial have been previously described . The mosSubjects with knee pain, unilateral or bilateral dysfunction, and diagnosis of primary knee OA, fulfilling the American College of Rheumatology criteria for clinical and radiographic diagnostics,  were eliClinicalTrials.gov (Identifier: NCT02698072) [The current study was approved by the Clinical Research Ethics Committee of the Rey Juan Carlos University, Madrid, Spain ; it was registered on 2698072) . All pat2698072) .One physiotherapist (MVOS) and the occupational therapist (VBC) carried out pain, function, and test assessments. Results were collected for pain intensity and function using the following tools: NPRS; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the Barthel Index (BI); and the timed up and go test (TUG). Sociodemographic data such as age, sex, and body mass index were collected. Chronicity of knee pain, calculated in months, was also noted. The primary outcome was the palpation intervention, while the secondary ones were pain intensity, function, and test assessments related to the presence of MTrPs in pain-OA patients.(1)Is there a taut band (or TB)?(2)Is there a palpable nodule in the taut band (NE)?(3)Is there a hypersensitive point (HN)?(4)Is there referred pain familiar to patient’s pain (RP)?The tensor fasciae latae, hip adductors, hamstrings, quadriceps, gastrocnemius, and popliteus muscles were examined in each subject following a protocol regarding patient and limb positions, exactly reproduced from the study of Mayoral et al. . These mWe had latent MTrPs when there was concurrence of the following 3 criteria: TB, NE, and HN. We had active MTrPs when all the four criteria were present ,30,32. PPain intensity was measured with the 11-point NPRS , where 0 corresponded to no pain and 10 to the worst pain imaginable. The NPRS is a valid and reliable tool, useful in elderly adults ,34. The In the TUG, patients stood up from a seated position on a standard chair, walked to a line on the floor three meters away, returned to the chair, and sat down again. The score was evaluated by the time taken in seconds to complete the test cut-off point of ≥13.5 . ConsecuData were analyzed using SPSS for Windows . Descriptive statistics (mean and standard deviation) were provided for all the subjects. The relationships between the number of active and latent MTrPs  of the six muscles examined  and pain or function were assessed using Pearson’s correlation coefficients. Then, the correlation between the number of trigger points was made, using the requirement of having active and latent trigger points with the clinical variables included in the study. Correlation coefficients with cut-off values of 0.3 and 0.7 were used to distinguish poor/moderate/good correlation.n = 165) consecutive subjects accepted to participate in this study. Seventy-one men and 43 women with knee OA aged from 65 to 86 years  satisfied all eligibility criteria. The reasons for ineligibility were rheumatoid arthritis (n = 11) and no confirmation of the diagnosis with radiographs (n = 39). Descriptive statistics for demographics, pain, and functional assessments, including mean values of NPRS, WOMAC, BI, and TUG scores, are presented in One hundred and sixty-five  and active MTrPs  in the hamstring muscles. Disability correlated moderately with the number of latent MTrPs in tensor fasciae latae muscle . The Pearson’s correlations between pain severity, disability, and the number of MTrPs variables are presented in Pain was measured with the NPRS scale and correlated poorly with the prevalence of latent MTrPs  had the highest prevalence of active MTrPs. The tensor fasciae latae showed the highest prevalence of latent MTrPs (50%). The analysis of correlation between pain, disability, and the presence of MTrPs was low and moderate for these two muscles, respectively.There was a significant difference in the total duration in months from the chronicity of pain among participants. However, in the cohort study developed by Neogi et al. , analyzin = 36), no useful comparison can be made with the results of the present study. Differences in results between our study and that of Alburquerque-Garcia et al. could perhaps be explained by the difference in sample size and/or gender, or that they compared 18 subjects affected by knee OA, diagnosed according to the American College of Rheumatology classification, with 18 asymptomatic subjects. In another observational study [n = 28: 14 patients with hip OA, Knee OA, or both, and 14 healthy subjects), a significant positive correlation between the total number of trigger points and their radiological scores was found ; unilateral knee joint OA patients had a greater number of MTrPs in muscles surrounding the knee joint, compared to the unilateral hip joint OA patients. These results contrast with the ones of the present study. However, due to the limited sample size in the previous study, a risk of bias exists. The authors of the previous study also found that the highest prevalence of MTrPs was observed in the gastrocnemius at 57.1%, whereas in our study, it was less, at 25%. Itoh et al. [Our results contrast with those of Alburquerque-García et al. , where tal study , also prh et al.  observedA previous study evaluating patients who were awaiting total knee arthroplasty surgery , found MDisability correlated moderately with the number of latent MTrPs in the tensor fasciae latae in our study; it should be noted that therapeutic improvements in pain are not always accompanied by improvements in functional parameters, as pointed out by White et al. . In theiIn a previous study, Neogi et al.  affirmedIt has been suggested that the myofascial pain syndrome, as well as central sensitization is at the origin of a persistent nociceptive input ,46, but The factors that mostly contribute to the development and progression of knee OA, are diet , socioecDifferent limitations were found in the study. The first and main limitation was the small sample size and the lack of a control group of participants. Another limitation was due to the symptoms of some patients that can worsen, as this behavior is identified as threatening or harmful. However, the present study did not evaluate depression or anxiety variables, sleep efficiency, or catastrophizing.The current study defined data about the prevalence of latent and active MTrPs in patients with knee OA, and found a poor correlation between pain and the presence of the MTrPs. The MTrPs prevalence points estimated in this study should be viewed with caution and future studies with large samples are needed. As such, we think that our results may open up a new way to investigate temporal pain, or conditioned pain modulation by active or latent MTrPs, to establish the contribution of active or latent trigger points to pain in knee OA. Therefore, there is a clear need for trials examining the potential role of treating MTrPs in patients with knee OA in a multimodal rehabilitative approach.This secondary analysis found that the prevalence of MTrPs varied from 11% to 50% in various muscles of patients with mild to moderate painful knee OA. Pain was correlated poorly with the prevalence of latent and active MTrPs in the hamstring muscles, and disability correlated moderately with the number of latent MTrPs in tensor fasciae latae.


This study aimed to conduct a randomized prospective study about the efficacy of etodolac and ibuprofen on trismus, pain and edema regarding gender of patients submitted to impacted lower third molar teeth extraction. Thirty patients aging between 16 and 35 year-old were submitted to the exodontia of impacted lower third molars. During the postoperative period, patients received nine ibuprofen (600 mg) or etodolac (300 mg) pills via oral administration immediately after surgery and repeated doses every eight hours during three days. Patients were evaluated regarding pain, trismus and edema. Sixteen men and fourteen women participated of the study. No statistical difference was established regarding gender according to the evaluated parameters. However, etodolac use showed better results regarding pain, trismus and edema. Pain, edema and trismus after impacted third molars extraction were not influenced by gender. Key words:Molar, third; sex, tooth extraction. Impacted third molar teeth removal is the most executed oral surgery procedure -3. HowevPostoperative pain is related to alterations in the central and peripheral nervous systems induced by trauma . This inClinical and experimental researches indicate that pain is perceived, evaluated and treated differently depending on gender, race/ethnicity and age of a person . When coAlthough, there are studies in the literature about pain perception regarding gender, there are still no studies about pain comparing genders after impacted third molars removal. Thus, this study aimed to execute a randomized prospective study about the efficacy of etodolac and ibuprofen on trismus, pain and edema according to the gender of patients submitted to impacted lower third molars extraction.This study was approved by the Research Ethics Committee of Araçatuba Dental School – FOA UNESP, under protocol number 818.680. Every patient signed the authorization term to the execution of the study and disclosure of results according to the medical and ethical protocol of the Declaration of Helsinki, 2013.Thirty healthy patients aging between 16 and 35 year-old participated of this study. Patients selection followed the adopted inclusion criteria: absence of systemic health problems and good oral hygiene; presence of bilateral impacted lower third molar teeth with extraction indication through ostectomy and odontostomy; teeth of both sides should present the same surgical difficulty level evaluated by panoramic radiographs, and present at least two thirds of the roots formed.Exclusion criteria for this study included smokers; systemic disease patients, such as diabetes, osteoporosis, hyperthyroidism, pregnant and lactating women; patients with hypersensitivity to ibuprofen, etodolac or dexamethasone; patients presenting third molars with different surgical difficulty levels between right and left sides; periodontitis; local infection or cysts and tumors.Sample size was obtained through the power of a test accomplished at the website www.lee.dante.br/pesquisa/amostragem/amostra, which indicated that a sample with nine patients per group would reach a power of 0.8. Thus, thirty patients were selected to participate of the study. Patients had both lower third molar teeth removed by the same surgeon with time interval of 21 days between both surgical procedures.Each patient took 4 mg dexamethasone one hour before the procedure. After the removal of the right or left lower third molar tooth, randomly chosen by the research assistant, each patient received 600mg of ibuprofen  or 300mg of etodolac  orally every 8 hours for 3 days, starting immediately after surgery. Each third molar tooth was removed in different moments with time interval of at least 21 days. Patients who received ibuprofen after the first surgery, received etodolac after the second surgery; and those who received etodolac after the first surgery, received ibuprofen after the second. All patients received 500 mg paracetamol pills to take every six hours in case of pain.The choice between right or left sides in the first procedure was defined using the website www.randomization.com, and both, surgeon and patient, did not know which medication was administered to the chosen side. The assistant was responsible for collection of data regarding the operated side and administered medication.- Surgical procedureAfter intraoral antisepsis using aqueous solution of 0.12% chlorhexidine gluconate and extraoral antisepsis with alcoholic solution of 0.5% chlorhexidine, the surgeon executed regional block of the inferior alveolar, lingual and buccal nerves using 4% articaine with 1:100,000 epinephrine .After local anesthesia, the surgeon made a full-thickness mucoperiosteal flap extended posteriorly to the second molar, and a relaxing incision in the vestibular region anteriorly to the same tooth. Flap detachment was executed using a Molt Periosteal Elevator No. 9 , ostectomy and odontostomy were made using an Oral Surgery Bur 702  connected to a high speed handpiece  under constant irrigation with saline solution.Teeth were removed using dental extraction forceps and the surgical wound closure was made using silk suture 4.0  with interrupted stiches. Suture was removed after 7 days.Postoperative care included eating cold soft foods and liquids within the first 48 hours, rest and mouthwash only after 24 hours. Patients who presented complications, such as bleeding, alveolitis or infection were excluded from the study. Patients were reassessed from 48 to 168 hours (seven days) by a third examiner who was not aware which group the patient belonged to. Pain, edema and trismus were evaluated.- Variable analysisPain: Pain level was evaluated through BS-11 analogue scale for pain  and the lower portion of the earlobe, using a measuring tape . Data waMeasurements were taken with patients in maximum intercuspation and relaxed lips. Each measurement was repeated 3 times in order to increase reliability of the method . Spots iTrismus: Trismus was evaluated by measuring maximum mouth opening using a digital pachometer , references used were the incisal edges of teeth 11 and 41. Measurements were taken before surgery, and 48 and 168 hours (7 days) after surgery.- Statistical Analysisp<0,05.Statistical analysis was conducted using SigmaPlot software . Shapiro-Wilk test was used to evaluate the normality of data distribution, followed by parametric and nonparametric tests application. Three-way analysis of variance was used to measure pain, trismus, edema and gender. Statistical significance considered was Thirty healthy patients, 16 men and 14 women, aging between 16 and 35 year-old participated of this study. Patients attended postoperative evaluations and no complications occurred during this period.Regarding pain, etodolac administration provided better comfort to patients, showing lower pain values than ibuprofen in all postoperative periods Fig. . This diIn both, ibuprofen and etodolac groups, edema peak happened in the first 48 hours, as expected. The group using etodolac presented lower edema coefficient than ibuprofen group Fig. . No statRegarding trismus, the lowest values occurred in the group using etodolac Fig. , the difPostoperative pain after impacted third molar teeth surgeries has become a model used by studies on acute pain , becauseet al. (According to a review by Fillingim et al.  about paet al. , colonoset al. , total het al. , knee aret al. , arthroset al. , and outet al. ,23. Thuset al. (A study by Bjørnnes et al.  regardinet al. .et al. (Chia et al.  studied et al. .In this study, female gender presented less pain sensitivity than men during postoperative period within the first 6 hours, different from the period of 12 and 24 hours after surgery. However, there was no statistical difference between groups.et al. (et al. (Regarding medication used, Bailey et al.  conducteet al. . Best et (et al.  observed (et al. . In thiset al. (Akbulut et al.  comparedet al. . Authorset al. .In this study, etodolac showed better results regarding edema, pain and trismus in all periods evaluated. No statistical difference was observed regarding edema and trismus between genders, presenting similar results between groups.This is a randomized mouth-split clinical trial with a reliable methodology in order to evaluate pain perception difference among genders. It was possible due to the standardization of third molar teeth removals, quantification of pain through a method published in the literature and, besides that, this is an unprecedented study due to the lack of studies published in the literature. However, this study presents some limitations regarding pain evaluation. Pain is subjective and is related to gender, age and ethnicity. Besides, other factors may influence pain perception, such as individual threshold and tolerance, and emotional state of the person. However, these limitations do not invalidate the study, because it is not possible to achieve this total control level in clinical trials.This study concluded that pain, edema and trismus after impacted third molar teeth extraction were not influenced by gender. Regarding the medication used, etodolac presented better postoperative results for the evaluated parameters. Despite results found, more studies are necessary to determine the role of gender in the postoperative period of oral surgery.


IntroductionAs total hip arthroplasty (THA) and total knee arthroplasty (TKA) transition to outpatient settings, appropriate pain management remains a challenge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may subvert the need for postoperative opioids. This study evaluated: 1) total opioid consumption; 2) postoperative pain intensity; 3) discharge destination; 4) length of stay (LOS); and 5) THA and TKA patients’ satisfaction in receiving adjunctive intravenous (IV) diclofenac or ketorolac.MethodsIn this retrospective cohort study, patients scheduled to undergo primary THA or TKA by a single surgeon between March 2017 and April 2018 were identified. Patients were stratified based on the receipt of IV diclofenac  or IV ketorolac  in addition to the standard pain management regimen. Student’s t-testing and Chi-square were used to analyze continuous and categorical variables, respectively.ResultsTKA diclofenac patients had lower opioid consumption 12 hours postoperatively (p: 0.037). TKA patients in the diclofenac cohort were discharged to home less often (p: 0.025). Both diclofenac cohorts had greater patient satisfaction than the ketorolac cohorts (p: <0.05). There was no significant difference between groups in postoperative pain intensity at 24 or 48 hours or in the length of stay .ConclusionThis study demonstrated that both TKA and THA patients treated with IV diclofenac had no difference in postoperative pain intensity while THA patients had no difference in opioid consumption relative to those treated with IV ketorolac. Further comparison of IV NSAIDs with other IV pain medications may provide broader insight into the ideal management for postoperative pain for this widening patient population. Total joint arthroplasty (TJA) poses a significant economic burden to the healthcare system, with combined inpatient costs for Medicare total hip and knee arthroplasties exceeding USD 7 billion in 2014 . As a reAlthough opioids have classically been a mainstay in the management of postsurgical pain, cognizance of their unfavorable side-effect profile and potential to prolong hospital stays has spurred initiatives to identify alternative pain-control avenues -14. A nuAlthough several studies have evaluated the efficacy of IV ketorolac and diclofenac on postoperative outcomes and pain control, there is a paucity of literature comparing the two in the setting of primary TJA. As such, this study evaluated: 1) total opioid consumption; 2) postoperative pain intensity; 3) discharge disposition; 4) length of hospital stay; and 5) satisfaction with adjunctive IV diclofenac or ketorolac pain control in primary THA and TKA patients, at a single institution between 2017 and 2018.Patient selectionInstitutional Review Board approval was obtained for all aspects of this retrospective cohort study. All patients that underwent TJA with a single surgeon between March 1, 2017 and April 31, 2018 were identified and screened for study inclusion. Patients were included if they had undergone a primary TKA or THA and received adjunctive diclofenac or ketorolac as a part of their postoperative pain management regimen. Patients were excluded from the review if they were on methadone therapy, had a history of chronic opioid use, had a low calculated creatinine clearance (less than 30 mL/min2), had undergone epidural anesthesia during their procedure, had a poor cardiac function, had an allergy to any NSAIDs, narcotics, or local anesthetics used in the study, or if they had undergone revision or conversion THA or TKA.We identified a total of 136 eligible TJA patients who had received IV diclofenac or IV ketorolac that were blinded to their perioperative pain regimen. The final patient cohorts comprised 25 THA patients and 51 TKA patients who had received postoperative IV diclofenac, and 28 THA patients and 32 TKA patients who had received postoperative IV ketorolac.Pain regimenThe standard pain regimen included: celecoxib 400 mg per oral (PO) preoperatively, then celecoxib 200 mg twice per day, starting on the evening of postoperative day one POD1) . The ketorolac group similarly received 30 mg of IV ketorolac every six hours for four doses upon arrival to the PACU. Oxycodone immediate-release (5 or 10 mg PO) was made available postoperatively to all patients in both groups to ease breakthrough pain if necessary.Study variablesDemographic information including gender, race, age, and body mass index (BMI) was collected for all patients. Opioid consumption [converted to morphine milligram equivalents [MME]), length of stay (LOS), visual analog scale (VAS) pain scores at eight-hour intervals, discharge destination, and post-admission satisfaction scores were collected to evaluate patient outcomes. Patient satisfaction with postoperative pain control was assessed via three questions selected from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey Table  25]..25].Pain intensity, expressed as area under the curve (AUC), was calculated utilizing VAS pain scores at eight-hour intervals through the 48-hour postoperative period.The THA patients in the IV diclofenac and IV ketorolac cohorts differed in race  and gender ; however, there were no differences in other demographic characteristics, including age  and BMI  .Statistical analysisChi-square analysis/Fisher’s exact test and Student’s t-test were utilized to analyze categorical and continuous variables, respectively. A p-value of less than 0.05 was designated as statistically significant. All statistical analysis was performed using IBM SPSS Statistics version 24 .For THA recipients, there was no significant difference between the IV diclofenac and ketorolac groups in mean total morphine milliequivalents (MME) opioid consumption at 12  or 24 hours  postoperatively  or POD2 , LOS , or discharge destination  ; “During this hospital stay, how often was your pain well-controlled?” ; and “During this hospital stay, how often did the hospital staff do everything they could to help you with your pain?” .For TKA recipients, patients in the IV diclofenac cohort had lower opioid consumption than patients in the IV ketorolac cohort during the first twelve hours postoperatively  , pain intensity on POD1  or POD2 , or mean LOS . The diclofenac group was less likely than the ketorolac group to be discharged home  (Table There was no difference in mean postoperative Knee Society Score (KSS) between the groups . Patients receiving diclofenac were significantly more satisfied with their pain control experience than those who received ketorolac Table .Specifically, IV diclofenac recipients answered “Always” more often than IV ketorolac patients in response to the questions “During this hospital stay, how well was your pain controlled?” ; “During this hospital stay, how often was your pain well-controlled?” ; and “During this hospital stay, how often did the hospital staff do everything they could to help you with your pain?” .Optimizing pain control regimens following TJA is an important aspect to help these procedures transition to the outpatient setting, as improved pain management can improve clinical outcomes and curtail costs . Due to There are some limitations to this study. As we only included procedures performed by a single surgeon at a single institution, the sample sizes are small. However, this was meant to be a preliminary study, reporting the early outcomes of IV NSAIDs in TJA. Additionally, data input and collection may have been susceptible to human error. To minimize this risk, data collection was limited to one investigator and the same nursing floor. Finally, satisfaction was significantly higher for the diclofenac group, despite similar outcomes. This could be due to the small sample sizes, as patients were blinded, and pain intensity was similar in all groups. Nevertheless, the present study is a great starting point for the investigation of TJA outcomes in patients receiving adjunctive IV diclofenac and IV ketorolac.Although TKA patients receiving IV diclofenac had lower opioid consumption at 12 hours, our findings revealed no difference in 24-hour opioid consumption for TKA and THA patients in the IV diclofenac and IV ketorolac groups. Other studies have reported on the comparative decrease in opioid consumption with both IV diclofenac and IV ketorolac. A double-blind, randomized control trial by Alexander et al. compared morphine consumption, as well as pain scores and opioid side effects, in 102 TKA and THA patients who were given IV diclofenac, IV ketorolac, or placebo preoperatively . They reThe present study demonstrated no differences in postoperative pain intensity or LOS between the IV diclofenac and IV ketorolac THA and TKA cohorts. Although prior studies have found decreased postoperative pain with the use of ketorolac and diclofenac in TJA, no study has demonstrated a significant difference between the two drugs. Etches et al. performed a multicenter, double-blinded, randomized controlled trial (RCT) comparing postoperative pain control between TKA and THA patients who received general anesthesia with placebo (n = 88) or with continuous infusion ketorolac (n = 86) . CompareAlthough patients in both THA and TKA diclofenac cohorts had increased satisfaction with IV diclofenac over IV ketorolac, outcomes were similar between the cohorts. Similar postoperative pain intensities and opioid consumption demonstrate the effectiveness of both drugs in managing postoperative pain. However, there are no studies comparing the cost of IV diclofenac to IV ketorolac for orthopedic surgery. In our institution, there is a vast pricing difference between IV diclofenac and IV ketorolac. The cost of four doses of IV diclofenac is USD 48.00, while the cost of four doses of IV ketorolac is USD 3.12. When extrapolated for 1,000 patients, the cost savings between these two drugs becomes apparent . This supports the utilization of IV ketorolac in postoperative pain management to yield the greatest cost savings. Nonetheless, the utilization of IV NSAIDs for pain management after TJA appears beneficial in reducing opioid consumption and may be well suited to supporting outpatient surgery in the future.Optimizing postoperative pain management is essential to improving clinical outcomes and reducing costs, especially as TJA moves out of the hospital. The addition of NSAIDs to the postoperative pain regimen is a promising way of decreasing opioid consumption and reducing postoperative pain. This study demonstrated that both TKA and THA patients treated with IV diclofenac had no difference in postoperative pain intensity while THA patients had no difference in opioid consumption relative to those treated with IV ketorolac. Further comparison of IV NSAIDs with other IV pain medications may provide broader insight into the ideal management of postoperative pain for this widening patient population.


The purpose of this study was to describe the symptoms experienced by patients with non-small cell lung cancer (NSCLC), examine whether different symptom groups significantly affected different functioning domains in these patients, and determine the effect of the “lack of energy” and “pain” symptom groups on the different functioning domains of health-related quality of life (HRQOL). From a single tertiary institution, this cross-sectional study enrolled 135 consecutive NSCLC patients who were mostly undergoing chemotherapy and were in the advanced stage . Clinical and self-reported demographic information and data on different functioning domains ), symptom experience (from the EORTC QLQ-LC13), and the Symptom Distress Scale (SDS) were examined. The four most common symptoms were fatigue (69%), pain (47%), dyspnea (38%), and lack of appetite (36%). The “pain” symptom group was negatively associated with physical, emotional, cognitive, and role functioning. The “lack of energy” symptom group was negatively associated with physical, role, emotional, social, and cognitive functioning. The “lack of energy” symptom group explained the most variance for physical and role functioning, and the “pain” symptom group explained the most variance for emotional functioning. Impaired concentration explained the most variance for cognitive functioning. Lung cancer (LC) is the most common cause of cancer-related deaths, and accounts for approximately 20% of all cancer-related deaths worldwide. Despite improvements in diagnosis and treatment, only 10.9% of individuals with LC live five years or more  and by 8Fatigue may co-occur with dyspnea in patients with LC, and this co-occurrence is associated with “lack of energy” . AdditioThe pain in patients with LC can be caused by the tumor itself, treatment, diagnostic tests, surgeries or procedures , local or metastatic invasion of a tumor into the chest and consequent inflammation or pulmonary embolism of the invaded area, as well as pressure on bones, nerves, or other organs . More spPrevious studies of LC have examined the relationship of the single symptom of fatigue and/or pain with HRQOL  and the Thus, we first classified the symptoms that significantly impacted HRQOL into two groups—a “lack of energy” group and a “pain” group—and then examined how these symptom groups affected patient HRQOL during treatment for non-small cell lung cancer (NSCLC). The results of this study may help clinicians in improving the HRQOL of patients undergoing NSCLC treatment and providing a better understanding of the significance of the different symptom groups on HRQOL in these patients.The specific purposes of this study were to (a) describe the symptoms experienced by patients with NSCLC; (b) determine whether different symptom groups significantly affected the functioning domains of patients with NSCLC; and (c) determine the contribution of each symptom group (“lack of energy” and “pain”) to the different functioning domains of HRQOL.This cross-sectional study enrolled 135 consecutive patients who were undergoing treatment for NSCLC at a single tertiary National University Hospital (652 beds) that specializes in cancer and elder health-care in Daegu, South Korea. Quota sampling was used to match the most recently reported male/female incidence ratio of LC in South Korea  [A review of the hospital electronic medical records indicated that 168 patients were potentially eligible from June 2017 to January 2018. Following clinical appointments, research staff personally contacted these patients at an outpatient clinic or in the admission ward and provided detailed information on the study and the right to refuse participation at any time. All patients had the opportunity to ask any questions about the study. Among 168 potentially eligible patients, 31 (18.5%) refused to participate. The most common reasons for refusal were concerns about privacy violation and the patient’s family did not want them to participate in the study. After a patient agreed to participate and signed the written informed consent agreement, a study questionnaire was distributed at the outpatient and inpatient facilities. All remaining 137 patients (81.5%) agreed to participate in the study, but 2 patients had incomplete responses on the main variables, and were excluded. Data from 135 patients (80.4%) were included in the statistical analyses.After signing the informed consent agreements, participants were asked to complete the questionnaire (a paper-based self-report). Outpatients completed the questionnaire immediately after recruitment, and inpatients were given more time to complete the questionnaire. Participants read and answered the questionnaire by themselves. Clinical data  were collected by review of the hospital’s electronic medical records. A research staff contacted patients by telephone if an incomplete response or missing data were noted in the questionnaire. The present study was the second study of a large project consisting of two small studies. The first study examined a multiple mediation model of spiritual well-being and will be published elsewhere . The parThe following instruments were used: (a) a self-reported demographic questionnaire, (b) the functional scale of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30), (c) the LC-specific symptom scale of the EORTC QLQ-LC13 module, and (d) the Symptom Distress Scale (SDS). The demographic questionnaire collected information on sex, age, marital status, caregiver characteristics, job status, monthly income, religion, educational level, and type of national health insurance. The clinical information included comorbidities, NSCLC stage and histological type, time since diagnosis, and current and prior treatments.Functioning in different domains was measured using the EORTC QLQ-C30 . This inAll symptoms specific to LC , to cancer in general , and related to treatment  were recorded.LC-specific symptoms and treatment-related side effects were assessed using the EORTC QLQ-LC13 module. This module has 13 questions, each rated using a 4-point Likert scale which ranges from 1  to 4 (very much), and is designed for use by patients receiving chemotherapy and/or radiotherapy. The LC-associated symptoms are cough, hemoptysis, and dyspnea; site-specific pain includes pain in the chest, arm and shoulder, and other parts. Treatment-related side effects are sore mouth, dysphagia, peripheral neuropathy, and alopecia. In this study, pain refers to pain in the chest, arm and shoulder, or other parts. The EORTC QLQ-LC13 module was validated at two international multicenter studies and has adequate reliability and validity . CronbacGeneral cancer symptoms were measured using the SDS ,30. The All scale and item scores for the EORTC QLQ-C30, QLQ-LC13, and SDS were linearly converted to ranges of 0 to 100 using the EORTC-QLQ-C30 scoring manual . A high Sociodemographic data, clinical characteristics, and symptoms are presented as numbers and frequencies using descriptive statistics. The occurrences of symptoms were estimated as follows. The symptom score >33 of EORTC QLQ-LC13 and ≥25 of SDS were considered to have the symptom. To find out confounders on the relationship between symptoms and functioning, the relationships of sociodemographic and clinical characteristics with the presence of 14 symptoms were determined using the chi-squared test. The associations between treatment modality and functioning domains were tested using one-way analysis of variance and Scheffe’s test. The relationships of functioning with the presence of symptoms were analyzed using analysis of covariance (ANCOVA) to control the confounders, and the general linear model was adjusted for age, marital status, caregiver status, practicing a religion, job status, monthly household income, education level, type of health insurance, comorbidities, time since diagnosis, NSCLC stage, and current and prior treatments. The results of the ANCOVA are presented as least-squares means (LSmeans). The associations of functioning with two symptom groups (“pain” and “lack of energy”) were determined. The pain symptom group was the sum of 5 symptoms in different regions: chest; arm and shoulder; other parts; peripheral neuropathy; and mouth. The lack of energy symptom group was the sum of 5 symptoms: dyspnea, lack of appetite, bowel pattern, dysphagia, and fatigue.2, β coefficient, p-value, and model R2. Statistical analyses were two sided; p-values less than 0.05 were considered statistically significant. All statistical analyses were conducted using SAS version 9.4 .Stepwise multiple regression analyses were used to identify the symptom group that had the greatest impact on each functioning scale of the HRQOL. The multiple regression model included the variables of “pain” and “lack of energy” symptom groups and all sociodemographic and clinical characteristics as independent variables. The results of the stepwise multiple regression analyses were partial RApproximately 70% of the patients were male, the overall mean age was 66 years, and 93% of the patients were married . ApproxiThe four most common symptoms were fatigue (69%), pain (47%), dyspnea (38%), and lack of appetite (36%) .p = 0.035). Patients without a spouse experienced more severe lack of appetite (p = 0.021); impaired concentration (p = 0.037); pain in the chest (p = 0.022), arm and shoulder (p = 0.036), and other parts (p = 0.049); dysphagia (p = 0.027); hemoptysis (p = 0.005); and dyspnea (p = 0.041). Patients with less education experienced more severe pain in the arm and shoulder (p = 0.028) and dysphagia (p = 0.048). Patients enrolled in Korea Medical Aid experienced more severe pain in the chest (p = 0.0003) and dysphagia (p = 0.041). NSCLC stage was associated with lack of appetite (p = 0.016) and insomnia (p = 0.032). Patients currently undergoing different types of treatments had differences in lack of appetite (p = 0.041), impaired concentration (p = 0.005), nausea (p = 0.006), bowel pattern (p = 0.047), and pain in the chest (p = 0.048). Patients who previously received different types of treatments had differences in concentration (p = 0.005), nausea (p = 0.0003), and peripheral neuropathy (p = 0.047). Histological type of LC was associated with differences in lack of appetite (p = 0.023), coughing (p = 0.001), dyspnea (p = 0.001), and peripheral neuropathy (p = 0.006) (Women experienced more severe fatigue than men (= 0.006) .p = 0.038) and the prior (p = 0.020) treatment types, respectively  and emotional functioning . Patients who experienced no pain in the arm and shoulder and other parts and no peripheral neuropathy had higher cognitive functioning . Patients who experienced no pain in other parts, no peripheral neuropathy, and no sore mouth had higher role functioning . Patients who did not have a sore mouth had better physical functioning (p = 0.005).Analysis of the “pain” group indicated that patients who experienced no pain in the chest, pain in the arm and shoulder, pain in other parts, and no peripheral neuropathy had higher physical functioning , role functioning  and emotional functioning . Dyspnea adversely affected social functioning (p = 0.026), and lack of appetite adversely affected cognitive functioning (p = 0.011). Patients who experienced no bowel disruption had higher physical functioning (p = 0.047), role functioning (p = 0.049), and cognitive functioning (p = 0.036). Dysphagia was associated with reduced cognitive functioning (p = 0.027), and fatigue was associated with reduced emotional functioning (p = 0.011).Analysis of the “lack of energy” group indicated that patients who experienced no dyspnea and no lack of appetite had higher physical functioning (p = 0.010), role functioning (p = 0.008), emotional functioning (p = 0.018), and cognitive functioning (p < 0.0001). Alopecia was associated with decreased emotional functioning (p = 0.014).Analysis of the two single factors indicated that impaired concentration was associated with decreased physical functioning , the “pain” symptom group , and receiving immunotherapy . Higher physical functioning was positively associated with more education  and having a job . Higher role functioning was negatively associated with the “lack of energy” symptom group  and impaired concentration . Higher emotional functioning was negatively associated with the “pain” symptom group  and receiving radiotherapy . Higher emotional functioning was positively associated with having a job . Higher cognitive functioning was negatively associated with the “pain” symptom group  and impaired concentration . Higher social functioning was negatively associated with the “lack of energy” symptom group , but positively associated with greater age  and higher income .Higher physical functioning was negatively associated with the “lack of energy” symptom group  and role functioning (18%), and the pain symptom group explained the most variance for emotional functioning (29%). Impaired concentration explained the most variance for cognitive functioning (28%) (The model Rng (28%) .The purpose of the current study was to determine the relationships of symptom groups with functioning domains of patients who had NSCLC and were undergoing treatment. For patients undergoing treatment, the four most common symptoms were fatigue, pain, dyspnea, and lack of appetite. Considering the significant relationship between symptoms and HRQOL, we established two symptom groups (“lack of energy” and “pain”) and one single symptom (“impaired concentration”). The “lack of energy” symptoms were associated with physical, role, and social functioning and explained the most variance for physical and role functioning. ”Pain” symptoms were associated with physical, emotional, and cognitive functioning and explained the most variance for emotional functioning. Impaired concentration explained the most variance for cognitive functioning.Our results indicated that the four most common symptoms experienced by patients with NSCLC during treatment were fatigue, pain, dyspnea, and lack of appetite. This result is supported by previous studies that examined patients with advanced LC who were undergoing treatment or palliative care ; patientWe found that fatigue was one of the most common symptoms, consistent with previous studies of patients with advanced-stage NSCLC . HoweverAfter fatigue, we found that pain (47%) and dyspnea (38%) were the symptoms with the highest prevalence rates. This result is similar to that of previous studies, which reported a prevalence rate of 49% for pain  and 39% Overall, our results showed that the “lack of energy” and “pain” symptom groups and impaired concentration negatively influenced HRQOL, in line with previous studies that reported negative relationships between symptom distress and HRQOL ,8. AmongRecent studies of LC have not sufficiently described the relationship between lack of energy and social functioning. However, previous research reported that severe fatigue seriously impaired engagement at work and participation in social and family activities, activities of daily living, self-care, and hobby and leisure activities ,38,39. TWe classified lack of appetite, bowel disruption, and dysphagia in the “lack of energy” symptom group. Our finding that the “lack of energy” symptom group influenced physical, role, and social functioning is consistent with a previous study that reported that undernourished patients had worse physical, social, and role functioning .The “pain” symptom group had the greatest influence on emotional functioning, but had less influence on physical and cognitive functioning. This result is consistent with several previous studies of patients with LC, which reported that the pain cluster  and painMost of our patients were receiving chemotherapy and had advanced-stage NSCLC, and 28% of them reported peripheral neuropathy. Peripheral neuropathy was in the “pain” symptom group, and affected physical and emotional functioning. Peripheral neuropathy is common in patients taking taxane- and platinum-based agents, which are commonly used by patients with advanced-stage NSCLC . GeneralFew previous studies of patients with LC reported a relationship between pain and cognitive functioning. However, previous studies of patients with cancer found that patients who had more pain had impaired cognitive functioning ,45,46,47Impaired concentration was a single symptom that had the strongest influence on cognitive functioning. Cognitive functioning included the following domains: attention and concentration, language , speed of processing , memory , and the effort and time needed to accomplish these tasks . These rAs in our study, some previous studies showed associations between more education and higher physical functioning among cancer survivors ,50. EducPrevious research reported associations of employment with higher physical  and sociThere is a widespread need to improve the functioning and alleviate the symptoms of patients with NSCLC. Symptom monitoring allows earlier detection of symptoms, adverse events, and their recurrence, so that interventions can be used to improve HRQOL and possibly prolong survival .The “lack of energy” group and the “pain” group affected different HRQOL functioning domains. It is important for oncology nurses to consider symptom groups, because the symptoms in a specific group had highly correlations with each other. In particular, patients can simply or generally express if they lack energy or feel tired or ill, but they have more difficulty in describing the experience of individual symptoms, such as dysphagia, diarrhea, anorexia, and peripheral neuropathy. Thus, an oncology nurse needs to understand a patient’s general symptoms and specific symptoms. When an oncology nurse critically analyzes the symptoms of a patient with LC, then comprehensive and preventive interventions that may improve the different HRQOL functioning domains can be applied. Nursing care based on symptom groups, monitoring of specific symptoms, and assessing disruptions of different functioning domains in daily life may facilitate the application of interventions that improve functioning and extend survival. We suggest that oncology nurses should give special attention to the HRQOL functioning domains of their patients by considering the two symptom groups identified here, namely “lack of energy” and “pain”.This study has several limitations because we used consecutive sampling of patients with NSCLC who were undergoing therapy in a single hospital that specializes in cancer. We made an effort to reduce selection bias by the use of consecutive sampling and matching of the LC incidence ratio of men and women in South Korea to reduce confounding bias due to sex. Moreover, because of the cross-sectional design of this study, our results only suggest the existence and factors that affect functioning at one point in time in a group of patients with NSCLC who were undergoing standard therapy. We cannot infer causal relationships of symptom groups with different functioning domains. Future longitudinal studies are needed to determine whether interventions that change the symptoms identified here alter different functioning domains. Despite these limitations, our study is an important contribution because the results showed that the symptoms of patients with advanced-stage NSCLC influenced different HRQOL functioning domains during the treatment period.This research studied patients with mostly advanced stage and receiving chemotherapy and found that the “lack of energy” symptom group was associated with the physical, role, and social functioning and explained the most variance for physical and role functioning. The “pain” symptom group was associated with emotional, physical, and cognitive functioning and explained the most variance for emotional functioning. Impaired concentration explained the most variance for cognitive functioning. These results indicated that different symptom groups had different effects on the functioning of patients with NSCLC who were undergoing treatment.


Patients with head and neck cancer often suffer from multiple and severe functional impairments. Swallowing, voice impairment and pain are often mentioned as mostly relevant for patients’ quality of life after treatment. The course of these specific functional impairments and related problems are not sufficiently observed. In our retrospective single-center cohort analysis of “real-world data”, collected in daily routine practice, we present data regarding the patient-reported outcome parameters of swallowing and voice problems and pain. Independent of tumor site and treatment regimen, patients reported less problems over time. Nevertheless, oropharyngeal tumors led to significantly more self-reported swallowing problems, while patients with larynx tumors more often had patient-perceived voice impairments. In addition, other clinical and sociodemographic variables had an impact on patient-reported function. The acquisition of patient-reported outcome data is valuable and a sufficient way to explore patients’ problems in a better manner. These data can help to improve patient care.n = 299) in an outpatient setting answered questionnaires  on dysphagia, voice problems and pain, collected with the software “OncoFunction” at three different timepoints (t1–t3) after diagnosis. The mean score changes from t1 to t3 were expressed in terms of effect sizes d. The impact of sociodemographic and clinical factors on the course of the variables was tested with multivariate analyses of variance. Results: Dysphagia, voice impairment and pain in HNC survivors significantly improved over a period of approximately 14 months after diagnosis. Tumor site, stage, treatment modality, occupational state and ECOG state were significantly correlated with self-reported functional outcome. The pain level of the HNC patients was rather low. Conclusions: Patients suffer from functional impairments after HNC treatment, but an improvement in self-reported symptoms could be demonstrated within this time period.Background: Head and neck cancer (HNC)-specific symptoms have a substantial impact on health-related quality of life. The aim of this study was to determine whether self-reported dysphagia, voice problems and pain of HNC patients changed over time and whether specific clinical or sociodemographic variables were associated with these symptoms. Methods: HNC patients ( Recent advancements in the detection and treatment of head and neck cancer (HNC) and the changing epidemiology, especially due to the rise in HPV-positive oropharynx cancer, have resulted in an increase in HNC survivors. The critical role of the head and neck in function as well as the partly complex treatment of HNC places survivors at high risk for HNC-specific symptoms that have a substantial impact on health-related quality of life. Tumor growth and infiltration of functional relevant tissue as well as consequences of surgery or radiation fibrosis often lead to severe functional impairments. Dysphagia, voice impairment and pain are typical symptoms that are often associated with social and psychological problems. These symptoms cause frustration and embarrassment, being common in the long term in HNC patients. Therefore, the assessment of patient-perceived dysphagia, voice problems and pain during and after HNC treatment is fundamental to measure the consequences of treatment over time. Studies have highlighted the importance of long-term swallowing and voice impairment, with a small number of studies specifically focusing on these issues ,3,4,5,6.As evaluation and treatment of short- and long-term side effects are important elements of comprehensive cancer survivorship care, we aimed to analyze the course of the self-reported symptoms dysphagia, voice problems and pain and to further investigate the temporal stability of these symptoms. We further aimed to analyze the impact of sociodemographic and clinical factors on the course of these symptoms.Patients’ data were obtained from the software “OncoFunction”. This database contains data from outpatients with head and neck cancer seen for regular follow-up appointments who were older than 18 years and have provided informed consent. This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.We included only those patients who were able to read and complete questionnaires on a tablet computer. Collection of the surveys began in June 2013. Every HNC patient in our outpatient setting used a touch-screen tablet computer to answer questionnaires focusing on HNC patients’ problems such as pain and swallowing, voice, breathing and psychosocial problems. They were asked to return the tablet to the nurses before they were called to see the physician. The staff were trained to assist the patients with the tablet computers circulated in the waiting room. A summary of the current responses along with prior responses was provided to the physician before the consultation. The usability of the system was demonstrated before . PresentPatients were retrospectively classified according to age, gender, occupational state, smoking status, alcohol consumption, tumor site and stage, type of treatment, presence of tracheotomy, presence of feeding tube, ECOG (Eastern Cooperative Oncology Group) state and body mass index (BMI).The standard of care for radiotherapy is intensity-modulated radiation therapy (IMRT) in our clinic. The majority of patients received platinum-based chemotherapy concordantly to radiotherapy in the adjuvant or primary treatment setting. A minority of patients received immunotherapy with cetuximab in their treatment regimens.The Eating Assessment Tool (EAT-10) is a 10-item questionnaire addressing the main aspects of dysphagia. The EAT-10 questionnaire addresses questions regarding loss of weight, swallowing effort, pain while swallowing, coughing and meals being stuck while eating and impaired social eating. It has been shown to correlate with findings on instrumental swallowing assessments such as a fiberoptic endoscopic evaluation of swallowing (FEES) ,17,18. PVoice problems were analyzed using the questionnaire “European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35” (EORTC QLQ-H&N35), a specific self-report questionnaire for HNC patients . The patPatients were asked to rate their current pain intensity on a numeric scale ranging from 0 to 10, with 0 representing “no pain at all” and 10 representing “maximal possible pain”.d. Pearson correlation coefficients were used to characterize the temporal stability of the variables. The impact of sociodemographic and clinical factors on the course of the variables was statistically tested with multivariate analyses of variance (ANOVAs). In these analyses, the factor time  served as a within-subject factor, and the clinical variable was considered the independent between-subjects factor. When clinical variables were analyzed in this way, age group and gender were additionally included as covariates. All statistical calculations were performed with SPSS version 24.The mean score changes from t1 to t3 were expressed in terms of effect sizes The sample consisted of 223 male and 76 female patients, and the mean age was 60.8 ± 10.2 years . d refer to the mean score change from t1 to t3; negative d values indicate a decline. r indicates the correlation between the t1 and the t3 scores.Mean scores and standard deviations of the variables are given in d = 0.55) was found for the first item (weight loss), which means that the patients gained weight. Voice problems and pain significantly reduced between t1 and t3.Among the 10 items of EAT-10, we observe a decline from t1 to t3 in eight items; the largest difference (rtt = 0.29) and item 1 .The coefficients of temporal stability of the three scales were between 0.46 (pain) and 0.59 (EAT-10 sum score), and the lowest stability scores were found for EAT-10 item 3 , this group was not considered in the diagrams. All figures indicate a decline in the symptoms. The results of significance tests for the independent factors  and for the factor timepoint are given in The effect of gender and age on patient-perceived dysphagia, voice impairment or pain was mostly not significant. Patients in the age group of 60–69 years reported significantly higher dysphagia values and patients older than 70 years had the lowest dysphagia levels. Behavioral factors such as alcohol consumption or smoking did not significantly influence dysphagia and voice problems. Smokers reported more pain than non-smokers; in both groups, pain decreased over time.Presence of metastasis and higher tumor stage did significantly influence dysphagia scores but not voice problems or pain. Patients with highest tumor stage (IV) and need of trimodality treatment (surgery + chemoradiation) reported the highest dysphagia scores over the complete follow-up. Voice problems and pain decreased from t1 to t3, independent of tumor stage or metastasis.Regarding feeding tube and dysphagia, there was a weak relationship. Patients with feeding tubes reported higher dysphagia scores. In the same direction, patients with the need for tracheotomy reported significantly higher voice problems. Patients with a tracheal canula and feeding tube reported higher pain scores, even if not reaching significance.Patients with better ECOG performance scores had less dysphagia and voice problems. Voice impairment significantly decreased in all ECOG groups. Patients with bad ECOG state also had higher pain levels; however, the difference was not significant. Pain levels decreased over time in all ECOG groups.Patients with lower BMI had higher dysphagia and pain scores, but these differences did not reach significance. Patients with a BMI lower than 20 reported significantly higher voice problems from t1 to t3 and also higher dysphagia scores. Dysphagia, voice problems and pain improved over time in all BMI groups.The presence of a feeding tube and tracheostomy  was alsoThis study provided data regarding the symptoms dysphagia, voice impairment and pain in head and neck cancer survivors in a short-term follow-up. The findings revealed that over a period of approximately 14 months after diagnosis of HNC, dysphagia, voice problems and pain significantly improved in our patient cohort.Dysphagia was analyzed using the EAT-10 questionnaire, which has previously been shown to correlate with objective swallowing examinations such as videofluoroscopy and FEES and seems to be an adequate instrument for the screening for dysphagia and aspiration in daily routine practice ,20,21. IPatients with oropharyngeal carcinomas showed higher dysphagia values at any given time than patients with other tumor sites. In the same manner, Carmignani reported significantly higher dysphagia in patients with oropharyngeal cancer compared to patients with larynx/hypopharynx cancer . AdditioPatients with a body mass index <20 reported the highest scores in the EAT-10 questionnaire. Insufficient supplementation could lead to weight loss and may explain the differences .The presence of feeding tubes from t1 to t3 was also explored. In total, 165 patients (60.4%) reported never having used a feeding tube, and 44 patients had to have their diet with a feeding tube all the time. Compared to t1, the feeding tube was removed at t2 in 39 patients and at t3 in 55 patients. This supports the statement that the course of dysphagia allows many patients an oral diet and better swallowing-related quality of life.The presence of tracheostomy tube also decreased over time in our patient cohort. Previous studies demonstrated that patients’ swallowing function correlates with time of decannulation, as one would expect, because only the exclusion of aspiration can prevent pneumonia and related problems . In our Patient-reported voice impairment significantly improved over the first three follow-up consultations. The same course was described in other publications, e.g., for transoral laser cordectomy . In thisConcerning pain, there was a significant improvement over time in our HNC patient cohort. Pain decreased in all examined items. Overall, the pain level was rather low in our cohort. This seems to be contradictory to results that characterized HNC patients by significant greater pain perception compared to other tumor entities . Bossi eWe could not detect a gender effect regarding the examined variables. Swallowing function, voice impairment and pain improved over time in men and women, independent of their gender. The impact of behavioral factors such as tobacco and/or alcohol consumption on the analyzed symptoms remains unclear. In the presented cohort, the data were inconclusive. Occupied HNC patients had significantly lower dysphagia and less voice problems at the analyzed follow-up points of time, than non-occupied patients. Whether patients with better function and less impairment are more frequently employed or whether employment leads to better patient-reported physical function remains unclear. However, the impact of employment status and the barriers to return to work after HNC were demonstrated in several studies ,34. In tConcerning ECOG state, our data are inconclusive. While dysphagia and voice problems were significantly correlated with ECOG status, pain was not; however, voice impairment and pain significantly improved over time depending on the performance status. This might be due to the potential of better compensation of functional limitations during the course with a better ECOG status.To explore the effect size of the variables of the EAT-10, voice and pain scale and to test the temporal stability, additional statistical analyses were performed. The highest effect size was shown for the question of weight loss and painful swallowing and the lowest temporal stability was shown for swallowing liquids and, again, weight loss. It has to be mentioned that the majority of questions showed high stability, and differences over time may be triggered only by a few questions. In further research, the possibility to reduce the questionnaire to some stable items could be examined.The strength of the present study is that all of the HNC patients were assessed using standardized and structured instruments.Nevertheless, the present study has some limitations, mainly due to its retrospective design. The reported data were self-reported, and while this has many benefits such as obtaining unfiltered patient data, a substantial bias through wrong reporting cannot be excluded. We tried to reach all patients in our aftercare consultation but may have excluded special patient groups such as illiterate patients or patients with Korsakow’s syndrome.Dysphagia, voice impairment and pain in HNC survivors significantly improved over a period of approximately 14 months after diagnosis. Tumor site, stage, treatment modality, occupational state and ECOG state were significantly correlated with functional outcome. The pain level was rather low in the analyzed patient cohort. These data show the value of patient-reported outcomes collected in the daily routine practice. The illustration of postoperative courses and knowledge about “normative ranges” can help to interpret patient-reported outcome data in the future.


Some patients may report moderate-to-severe pain and/or swelling following root canal treatment, which is undesirable for both the patient and dentist and may require an unscheduled emergency visit by patients to relieve their symptoms. The aim of this study was to evaluate the post-treatment flare-up incidence following application of nano zinc oxide-eugenol (NZOE) sealer in mandibular first molars with irreversible pulpitis. This single-blinded study was performed on 60 patients having mandibular first molars with irreversible pulpitis. After signing the written consent form, the patients were randomly divided into two groups considering their age range (20-34 and 35-50 years). Individuals without systemic diseases and with a ﬁrst mandibular molar diagnosed with irreversible pulpitis due to caries, no sinus track and abscess, normal periapical radiographic appearance, no spontaneous pre-treatment pain, not taken any medication for at least 8 hours before the treatment visit were included in this study. Patients of both sexes with age range of 20 to 50 years were selected. In order to obturate the root canal space, AH26 sealer was used in the one group and the synthesized NZOE was applied in another group. The patients were then given questionnaires to report the severity of pain and presence of swelling during 6, 18, 24, and 48 hours of follow-up. The data was analyzed using SPSS v.19 software applying repeated measures ANOVA. The significance level was set at 0.05.p= 0.003). Patients reported no symptoms of swelling in any group.  The severity of pain was significantly lower in NZOE group at 24 hours post-treatment ( NZOE sealer manifested satisfactory results and could be regarded as a promising substitute to routine sealers since patients may experience less pain during the first hours after receiving root canal therapy. These objectives are provided through complete cleaning, shaping, and obturation of canals of affected teeth  . Howevene week  . Althoune week  . In addne week  . In addne week  - 8. et al. [ et al. [ In obturation of the root canal system, sealer is used to prevent penetration of microorganisms and their byproducts. In the other hand, sealer is in direct contact with periapical tissues and may cause inflammation, tissue degeneration, and delay in wound healing. Therefore, the ideal root canal sealer should be non-cytotoxic, non-mutagenic, and immunologically compatible with periapical tissues  . Currenet al.   demonst et al.   showed  et al.  .Recently, a new endodontic sealer with nano-sized ZO powder particles (NZOE) has been developed in the Dental Material Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. This sealer is similar to various ZOE-based sealers, but with different sizes of ZOE nanoparticles. In previously published articles, we verified that NZOE sealer had less microleakage and better antibacterial property in comparison with Pulpdent and AH-26 sealers  . In an ZOE -based sealers are the oldest sealer used in endodontic therapy. Zinc oxide (ZO) is a valuable component of these sealers that is very effective as an antimicrobial agent. Many reforms have been done on these sealers in order to improve their properties and many commercial models are available  . In addTo the best of our knowledge, the use of nano-structured materials as sealers in root canal therapy is limited to two or three types of nano-structured hydroxyapatite alone or in combination with epoxy resin   - 22.No evidence-based investigations have evaluated postoperative pain and swelling when different sealers are used for obturation. The aim of this study was to assess postoperative pain and swelling in a prospective randomized clinical trial following the use of AH-26 and NZOE as a sealer in mandibular molars with irreversible pulpitis that were treated in one visit.The Ethics Committee of Mashhad University of Medical Sciences  approved the protocol of this study.In this work, ZnO nano-powders were prepared by a modified sol-gel method, using gelatin  .To prepare 5 g of the final product, first a solution of gelatin  was prepared by dissolving 10 g of gelatin in 150 mL of deionized water at 60°C. Then, appropriate amounts of zinc nitrate (Zn (NO3)2 .6H2O; Merck %99) were dissolved in minimum deionized water at room temperature. Then, the two solutions were mixed and stirred for 8 hours while the temperature was kept at 80°C. Finally, the pure resins were calcined at different temperatures of 500, 600, and 700°C to obtain ZnO nano-powders. Morphological and structural properties of the prepared ZnO were characterized by x-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques.The sample size was calculated based on an alpha of 0.05 with power of 80%, indicating that 27 patients would be required in each group but after considering the dropout rate of 10%, the sample size increase to 30 patients in each group. Inclusion criteria were as follows: individuals without systemic diseases and with a ﬁrst mandibular molar diagnosed with irreversible pulpitis due to caries, no sinus track and abscess, normal periapical radiographic appearance, no spontaneous pre-treatment pain, not having taken any medication for at least 8 h before the treatment visit. Patients of both genders ranging from 20 to 50 years of age were selected. During the root canal procedure, teeth that could not be treated in a single visit or patients who interrupted treatment were excluded. In addition, the patient with severe periodontal disease, over instrumentation or overﬁlling beyond the root canal space, teeth that could not be isolated with rubber dam, root canal calciﬁcation, root resorption and teeth that were not suitable for further restoration were excluded. All the treatment procedures were performed by a postgraduate student in the Endodontic Department, Mashhad Dental School, Iran, from May to August 2018. A total of 60 teeth were randomly assigned to two groups using a random-digit table. Before initiating treatment, the patients were asked to rate their pre-treatment pain on a visual analogue scale from 0 to 9. For each number, one of the sealers was selected. Each patient chose one of the numbers, and based on the number, the nurse supplied one of the sealers for the treatment visit. Since two sealers were different in their shape and appearance, the practitioner could not be blind. Prior to beginning of the root canal treatment, inferior alveolar nerve block injection was done with 2% lidocaine with 1: 80 000 epinephrine. After isolation with a rubber dam, followed by access cavity preparation, working length was determined with a Raypex6 apex locator  and then it was conﬁrmed radiographically. After preparing the root canals with hand instruments to at least a size 15 K-ﬁle , Hero rotary instruments  were used for root canal preparation. Apical patency was performed with a size 10 K-ﬁle between each rotary instrument. The apical preparation was completed up to size 30, .04 taper. Between instruments, the root canals were irrigated with 3 mL of 5.25% NaOCl with a 30-gauge side perforated needle . During irrigation, the needle was repeatedly moved up and down to prevent locking in the canals. The smear layer was removed by irrigating with 3 mL 17% Ethylene diamine tetra acetic acid (EDTA)  followed by 5 mL normal saline irrigation at the end of root canal preparation. The root canals were dried with paper points . Then in the group 1, the canals were ﬁlled with gutta-percha (Meta Biomed Co.) and AH26  sealer and group 2 was filled with gutta-percha and NZOE sealer using the cold lateral condensation technique. Each patient was given a numerical visual analogue scale (VAS) form to record the severity of pain from 0 to 9 during the 6, 18, 24, and 48-hours period following treatment, and the other form was used to record swelling. In the second form, the following scores were used: 0 for none swelling, and 1 for swelling. The data were analyzed using SPSS v.19 software applying Chi-square and Kendall’s Tau-b. The significance level was set at 0.05.Based on the inclusion and exclusion criteria, a total of 64 patients were eligible to participate in the study.Four patients from both groups were excluded from study since treatment could not be completed in one visit for one patient;two patients did not return the VAS form, and one patient had partial necrosis pulp. Finally, 60 patients were includedfor data analysis (30 in each group. The age and sex distribution of patient in each group was reported in et al. [ In the present study, the results of single-visit root canal treatment of mandibular first molars with irreversible pulpitis with the use of AH26 and NZOE as root canal sealers showed that the NZOE was associated with statistically signiﬁcant less pain at the 24 h after treatment. Moreover, postoperative pain intensity decreased with time within both groups that was in agreement with the findings of Parirokh et al.  . In botIn the present study, for prevention of possible bias, patients with similar preoperative conditions were included. As the preoperative pain would have a signiﬁcant effect on postoperative pain  , only pVarious methods were used for evaluating the effect of different variables on postoperative endodontic pain. In the present study, a VAS was used to compare postoperative pain intensity because it is a simple tool with high reliability and validity and more sensitive to small changes than descriptive ordinal scales  .There are some studies on the effect of irrigation type   and irrOver-instrumentation, excessive amount of sealer, the excessive compaction force, hydrostatic pressure, the use of lentulo spirals, immature canal apices, and root tip resorption can increase the risk of sealer extrusion  .et al. [ et al. [ In this study, the most post-operative pain was reported by AH 26 group during the 24 h after treatment. This can be due to mild-to-moderate irritating effects of AH26 when freshly prepared and the toxicity is due to the release of a small amount of formaldehyde, epoxide bisphenol resin, or amines during the chemical setting process  . In addet al.   reveale et al.   reporte et al.   and on  et al.   was lowAccording to the result of the present study and considering the lesser microleakage and better antibacterial property of NZOE in comparison to AH-26 sealers   and conUp to 24 h following root canal treatment, the use of NZOE sealer was associated with signiﬁcantly lesser pain than the use of AH26 in studied patients.