To assess the presence of a seasonal effect on fatigue, pain and dryness in primary Sjögren’s syndrome (pSS).n = 103 patients), hydroxychloroquine  and rituximab  and from the 5-year follow-up of the ASSESS prospective cohort (n = 395 patients). Data were analysed at each visit for each patient, according to the day, the month of the year and the season. Linear mixed models were used to take into account the repeated structure of the data and to analyse a potential cyclic effect.Data  for pain, fatigue and dryness) were extracted from three randomised placebo-controlled trials (RCTs) evaluating infliximab .A total of 744, 584, 848 and 682 pain, fatigue and dryness VASs were collected on 632 subjects in spring, summer, fall and winter, respectively. No significant difference was observed in pain, fatigue and dryness, according to the month of the year or the season  on fatigue, pain and dryness. Seasonality in rheumatic diseases is an issue frequently perceived and voiced by patients. Several studies have identified weather-related flares in rheumatoid arthritis (RA) , 2. WeatIn addition, cyclic seasonal variations have been associated with disease onset and activity or worsening of symptoms in immune-mediated inflammatory diseases (IMIDs), in giant cell arteritis (GCA) , inflammHowever, seasonality has not been investigated in primary Sjögren’s syndrome (pSS) yet. Primary Sjögren’s syndrome is the second most frequent systemic auto-immune disease, and it is clinically characterised by the disabling triad pain, dryness and fatigue and is immunologically associated with antinuclear antibodies, anti Ro/SSA and/or La/SSB and the presence, in up to one third of the patients, of ectopic lymphoid structures developed in the target organs of the disease, which are mainly salivary and lacrimal glands .Since fatigue, pain and dryness represent most of the disease burden shared by all patients with pSS, they compose the internationally validated ESSPRI (EULAR Sjögren’s Syndrome Patient Reported Index) score , an outcAlthough fatigue, pain and dryness represent a major concern for patients with pSS, there is no data available in the literature regarding the potential variations of these symptoms according to seasonality.Based on previous reports that have demonstrated, in RA, a worsening of pain and fatigue in winter and an increase of dryness in spring in dry eye symptoms unrelated to pSS, it could be hypothesised that fall and winter are associated with increased fatigue and pain and spring and summer with exacerbation of ocular and oral dryness in pSS.This study was therefore conducted to assess whether seasonal variations have an influence on pSS outcomes.n = 395)  (p = 0.89) and 0.75 CI 95% [0.38–1.53] (p = 0.35) in spring, summer and winter, respectively, in comparison to values collected in fall. Treatment regimens did not show any influence on salivary flow either, since aOR of having a pathological salivary flow (SF < 0.1 mL/min) was 1.23 CI 95% [0.49–2.64] (p = 0.58), 0.71 CI 95% [0.24–1.43] (p = 0.38) and 0.83 CI 95% [0.34–1.68] (p = 0.6), in spring, summer and winter, respectively, in comparison to values collected in fall  of potential confounding factors, such as age of patients, symptomatic treatments of dryness and systemic immunomodulatory treatments. Adjusted odds ratios (aOR) on age and treatment regimens did not detect any statistically significant seasonal effect on Schirmer test, with aOR of having a pathological Schirmer test (≤5 mm) of 0.93 CI 95% 0.42–1.8] (.8 (p = 0p = 0.4), 0/100 CI 95%  (p = 0.99) and − 0.3/100 CI 95%  (p = 0.83), in spring, summer and winter, respectively, in comparison to values collected in fall. Adjusted fatigue VASs variations were 1.3/100 CI 95%  (p = 0.33), 0.4/100  (p = 0.79), and − 0.2/100  (p = 0.84) in spring, summer and winter, respectively, in comparison to values collected in fall. Adjusted dryness VASs variations were 1.3/100 CI 95%  (p = 0.27), 2/100 CI 95%  (p = 0.09) and 0.6/100 CI 95%  (p = 0.55), respectively, in comparison to values collected in fall. Finally, adjusted ESSPRI score changes were of 1.2/100 CI 95%  (p = 0.25), 0.6/100 CI 95%  (p = 0.55) and − 0.2/100 CI 95%  (p = 0.82), respectively, in comparison to values collected in fall , might suggest an association between disease activity and season changes. Of note, previous studies have postulated that low levels of vitamin D, because of its immunomodulatory effects, could affect clinical manifestations in patients with pSS [A seasonal pattern of several suspected environmental triggers, such as viral infections (EBV and CMV in winter and HBV and HCV in spring and summer) as well as sunshine exposure  for dryness, pain and fatigue, which are − 10, − 10 and − 20 on a 100-point scale, respectively .Nevertheless, this study has several limitations. First, patients included in the ASSESS cohort underwent an annual evaluation of their symptoms and activity, mostly at the same period every year. However, the three trials lasted 1 year and visits were scattered all over the year. In addition, the statistical analysis not only focused on the intra-individual but also assessed the inter-individual seasonal variability of symptoms.Several confounding factors, such as age, symptomatic treatments of dryness and immunomodulatory treatments assumed by patients, could have hampered the interpretation of the results. To address this point, linear mixed models were adjusted to take into account the influence of age and treatments on objective assessment of ocular and oral dryness and on PROs, in the ASSESS cohort. Adjusted analyses on age, immunomodulatory drug exposure and symptomatic treatments of dryness did not reveal any statistically significant effect of seasons on objective dryness outcomes. Furthermore, even when adjusted on age and treatments, there was no significant effect of seasons on fatigue, pain and dryness VASs or on the ESSPRI score either.Other limitations include the unavailability of weather variables such as temperature, relative humidity, barometric pressure, sunshine exposure, precipitations and the variability of geographic locations (multicentric studies). A longitudinal study involving meteorological features and assessing pSS outcomes every months during several years, as recently performed in RA , could bThis first large study on seasonality in pSS provides new evidence that fatigue, pain and dryness, as well as the ESSPRI score, do not have meaningful fluctuations according to months or seasons. In pSS, seasonality does not affect patient-reported outcomes (PROs) on fatigue, pain and dryness.Additional file 1:Table S1. Drug regimens used at enrolment in the ASSESS cohort and number of patients with systemic immuno-modulatory drugs and symptomatic treatments of dryness. Table S2. Influence of seasons on objective assessments of ocular and oral dryness . Table S3. Variations of pain, fatigue and dryness VASs  and of the ESSPRI score according to seasons, adjusted on age, immunosuppressive treatments and symptomatic treatments of dryness.


In this study, we investigated the relationship between sensory abnormalities evaluated by quantitative sensory testing (QST) and alexithymia, depression and anxiety in patients with neuropathic pain involving the upper limbs. We enrolled 62 patients  and 48 healthy controls. All underwent nerve conduction studies (NCS), evaluation of cold, heat pain and vibration detection threshold (VDT) by QST and evaluation of alexithymia by Toronto Alexithymia Scale (TAS-20), depression by Beck Depression Inventory II (BDI-II), anxiety by State-Trait Anxiety Inventory (STAI-Y), level of psychological distress by 12-item General Health Questionnaire (GHQ-12) and perceived social support by the Multidimensional Scale of Perceived Social Support (MSPSS). The general linear model analysis revealed a significant relationship between TAS-20 overall and TAS-20 sub-score for difficulty identifying feelings and VDT z-scores in the left index with no interaction by year of education and sensory NCS results. Our results demonstrated the association between impairment of vibratory sensation of the left hand, reflecting cutaneous mechanoceptor dysfunction, and alexithymia, particularly the difficulty to identify feelings. The importance of delivering to patients with neuropathic pain personalized care that takes into account not only the neurophysiological aspects but also the aspects of mental functioning is discussed. The International Association for the Study of Pain (IASP) defined pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” IASP . Mood ana: loss, lexis: word, thymia: mood or emotion) is a personality construct characterized at an intrapersonal level by an impairment in identifying feelings, inability to find appropriate words to describe them, restricted imagination with a lack of fantasy and heightened preoccupation with the external details of events  peripheral neuropathic pain  underwent a full clinical evaluation, including a Medical Research Council (MRC) scale score , heat-induced pain (HPT), and vibration (VDT). CDT, HPT and VDT were evaluated at the palmar surface of the index and little finger; CDT and HPT were also evaluated at the dorsum of the hand. VDT, CDT and HPT were evaluated with a commercially available thermal and vibratory stimulation device . HPT was evaluated by the method of limits  . The BDI-II is a 21-item validated self-report instrument assessing depressive symptoms over the previous 2 weeks  was used to assess the presence of anxiety symptoms  is a self-report questionnaire assessing levels of psychological distress  is a validated self-report measure of subjectively assessed social support . The normality of the quantitative parameters distribution was analyzed using the Kolmogorov–Smirnov test, and the QST parameters that were non-normally distributed were log-transformed to be analyzed using parametrical methods of inferential analysis , due to a significantly higher number of patients with primary  and secondary school licenses  and a lower number of graduates . In patients,  APB and ADM MRC scores were lower than in healthy controls both on the right and left side . Neuropathic pain involved hands bilaterally in 30 patients, the right hand in 16 and the left hand in 16. All patients and controls were right handed. The mean NRS was 6.2 ± 2.4 and DN4 was 5.4 ± 2.2, and did not differ among CTS, PBHS and ONP . Itching, burning pain and mechanical allodynia were significantly more frequent in PBHS , tactile and pinprick hypoestesia were significantly more frequent in ONP  and tingling was significantly more frequent in CTS .Thirty-four patients had CTS , 7 BP , 3 PR C5-C6 , 5 UNE  and 13 PBHS. No difference between patients and healthy controls was noted either for age (52.7 ± 13.6 vs 48 ± 15.5 years) or sex . The data of patients with BP, PR and UNE were pooled and considered as other neuropathic pain of the upper limb (ONP). Years of education were significantly lower in patients than healthy controls . No difference was noted between painful and non-painful hand for median (p = 0.63) and ulnar SCV (p = 0.91), median (p = 0.62) and ulnar SAP amplitude (p = 0.24). The median motor conduction velocity was significantly lower in patients than in healthy controls  and median motor latency was higher in patients than in healthy controls  (see Table Results of sensory NCS are summarized in the Table n p = 0.6 and ulnap = 0.01) and ONP  while L3 is more frequent in ONP than PBHS ; G2 is significantly more frequent in PBHS than CTS .QST results are summarized in Table All psychological, health quality and social support evaluations did not differ significantly between CTS, PBHS and ONP. When patients were considered together, they had significantly higher STAI-Y1, BDI-II, TAS-20 overall, TAS-20 F1, TAS-20 F3, and GHQ-12 values than healthy controls , STAI-Y2 , BDI-II , TAS-20 F1 , TAS-20 F2  and TAS-20 F3 . TAS-20 F1 correlated with STAI-Y1 , STAI-Y2 , BDI-II , and GH-12 . The GHQ-12 score correlated with STAI-Y1 , STAI-Y2 , BDI-II . The BDI-II score was significantly correlated with STAI-Y1 , STAI-Y2 .TAS-20 overall correlated with STAI-Y1 , TAS-20 F1 . Left hand CDT z-scores were correlated with NRS . Left hand HPT z-scores were correlated with STAI-Y1 , and STAI-Y2 . Right hand HPT z-scores were correlated with STAI-Y1 . Alexithymic patients had higher VDT z-scores in the left index  and left little digit  than borderline alexithymic and non-alexithymic patients. No significant difference in TAS-20 overall, TAS-20 F1, TAS-20 F2 or TAS-20 F3 was evident between patients with pain only affecting the right hand and those with pain only affecting left hand . There was a significant inverse correlation between TAS-20 overall, TAS-20 F1 scores and both the left median  and left ulnar SAP amplitudes .In patients, left hand VDT z-scores were significantly correlated with TAS-20 overall . Post hoc analysis showed a significant difference of TAS-20 F1 between L0 and L2/3 (p = 0.008).When alexithymia was compared according to sensory phenotype, there was an overall difference of TAS-20 F1 among L0, L1, L2 and L3 without any interaction by the diagnostic group . Years of education did not influence the relationship between VDT z-scores and either TAS-20.The GLM analysis revealed a significant relationship among left index VDT z-scores and TAS-20 overall TAS-20 F1 and left median SAP amplitude , as well as both state and trait anxiety (HPT), further supporting the association between emotional processing and perception.Taken together, these observations suggest that psychological features, including emotional processing, could be interpreted also taking into account QST results and NCS. QST has been evaluated as a potential biomarker for neuropathic and non-neuropathic pain, and may help to identify a possible pathophysiological mechanism underlying pain in a patient, thus guiding treatment (Smith et al. In our study, we did not find any relationship between alexithymia and pain intensity: NRS was correlated with CDT, in keeping with previous reports suggesting the critical role of small fibers in the pathophysiology of neuropathic pain (Truini et al. In contrast, alexithymia was correlated with VDT and ulnar and median SAP amplitude, thus supporting a distinct mechanism. The association between the difficulty identifying feelings and measure of psychological distress, which is not the case for pain intensity, is interesting and may warrants further investigation.Taken together, our results suggest a relationship between sensory impairment expressed by QST and NCS results and alexithymia and perceived social support, and that alexithymia is related to health quality in patients with neuropathic pain, independently of the intensity of pain itself.This study has some limitations that should be considered. First, we used self-reported instruments for the assessment of psychological, health quality, and social support variables. With regard to alexithymia, this may have led to an underestimation of the presence of participants with alexithymia, in particular of individuals who scored close to the cut-off scores. Structured interviews, less dependent on the individuals’ awareness levels, should be used, in addition to the traditional TAS-20 questionnaire. Second, we adopted a cross-sectional design, which does not allow us to draw firm conclusions with regard to the causality of the emergent relationships. Third, even though we enrolled an adequate number of participants, our study is limited by a relatively small number of participants, and future studies should recruit a larger number of participants. Fourth, we found an association between alexithymia and both VDT and sensory phenotype with prominent loss of mechanoceptor function, but further studies are needed to evaluate a possible causal relationship.Despite the limitations described, the current study sheds new light on the correlation between sensory phenotype and alexithymia in patients with neuropathic pain in the upper limbs. Based on these results, we suggest the importance of delivering to these patients personalized care that takes into account, from a biopsychosocial perspective, not only the neurophysiological aspects but also aspects of their mental functioning, especially with regard to their capacity to identify and describe feelings.


BPI) average pain scores by patient global impression of improvement (PGI‐I) category and the cut‐off for clinically important difference (CID) were different between Asian and Caucasian patients with chronic pain due to osteoarthritis. This analysis used data from 3 (Caucasian) and 2 (Asian) randomized, placebo‐controlled, 10‐ to 14‐week duloxetine studies for the treatment of patients ≥40 years of age with osteoarthritis pain. The receiver operating characteristic (ROC) analysis was used to characterize the association between changes in BPI average pain scores and PGI‐I levels at study endpoint. The CID was characterized by PGI‐I, and the cut‐off point for CID in BPI average pain scores was determined by the intersection of a 45‐degree tangent line with each ROC curve. Data from 668 Asian and 868 Caucasian patients were available for analysis. Baseline BPI average pain ratings including worst and least pain were comparable between Asians and Caucasians. Ratings for percentage change from baseline to endpoint for BPI average pain scores in Asian patients and Caucasian patients were similar across the 7 PGI‐I categories, regardless of age, gender, study, and treatment. The ROC analysis results of cut‐off points in BPI average pain scores demonstrated the raw change cut‐off was −3.0, and percentage change cut‐off was −40% for both Asian and Caucasian patients. Overall, the present analysis concludes changes in BPI average pain scores by PGI‐I category and the cut‐off for CID were similar for Asian and Caucasian patients with chronic pain due to osteoarthritis.The objective of the present analysis was to determine whether changes in Brief Pain Inventory ( Osteoarthritis (OA) is one of the most prevalent chronic musculoskeletal disorders worldwide, especially in the elderly.Ogawa et al.Clinical pain studies have demonstrated cultural variations in response to painful stimuli.Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine in the central nervous system and is efficacious for chronic musculoskeletal pain.This analysis used data from 3 (Caucasian)In all studies, the BPI ratings for worst, least, and average pain intensity were collected at baseline, and the BPI average pain and the PGI‐I ratings were collected at several post‐baseline visits. The analysis was carried out using the values collected at the last visit of the double‐blind treatment phase. The percentage change from baseline in BPI average pain severity using the 0‐to‐10 numeric scale compared to the 7‐category PGI‐I assessment at study endpoint was computed for each patient. The relationship between percentage change in BPI scores and the endpoint PGI‐I scores was plotted by displaying the BPI average change within each PGI‐I category. Two categories on the PGI‐I scale, “very much worse” or “much worse,” were combined because of the small numbers of patients in these groups. Reduced calculations for BPI average pain scores from baseline to endpoint by PGI‐I category, according to race (Asian and Caucasian) and study participation, were evaluated. In addition, subgroup analyses by age groups , gender , and study treatment group (duloxetine vs. placebo) were performed to explore whether they influence or confound PGI‐I distribution between the races. Moreover, the percentage change from baseline in BPI average pain scores by PGI‐I category according to race (Asian and Caucasian) in duloxetine‐treated patients was assessed. All comparisons were made using descriptive statistics. The percentage change data are summarized in graphical format, while results from receiver operating characteristic (ROC) analysis are presented in tabular format.In the present analysis, 3 different levels of improvement as characterized by the PGI‐I were examined: “a little better” or higher ; “much better” or higher (PGI‐I score = 1 or 2); and “very much better” (PGI‐I score = 1). CID was characterized by the PGI‐I and was defined as “much better” or “very much better.” The ROC curves were generated by computing the sensitivity and specificity in a contingency table (2 × 2) for both the raw and percentage changes for BPI average pain scores, and for each level of the PGI‐I, using the proportion of patients who reported each possible level of change in pain rating as the exposure and the preselected level of the PGI‐I as the outcome. The appropriate cut‐off point for the BPI average pain percentage change was determined using ROC analysis. ROC analysis is a standard statistical analysis used to best characterize the association between change in the BPI average pain score (independent variable) and different levels of the PGI‐I (dependent variable) at the study endpoint. The cut‐off point for CID was determined by the intersection of a 45‐degree tangent line with each ROC curve; thus, the pain intensity changes can be best associated with each of the categories of improvement on the PGI‐I.Data from 668 Asian and 868 Caucasian patients, who had recorded baseline pain intensity and at least 1 post‐baseline measure on the BPI and PGI‐I, were included in the analyses. A summary of patient demographics and baseline characteristics of the combined studies is presented in Table The ratings for percentage change from baseline for BPI average pain scores were similar across the 7 PGI‐I categories for Asian and Caucasian patients Figure . Asian aTable The present analysis of pooled data from 5 studies of duloxetine in patients with chronic pain demonstrated a close association between changes in BPI average pain scores and PGI‐I scores in Asian and Caucasian patients. In Asian and Caucasian patients, the relationship is highly consistent across all analyzed studies, the treatments administered (duloxetine or placebo), and the patient demography characteristics (age and gender). The BPI average pain (percentage) reduction from baseline to endpoint was similar across 7 PGI‐I categories for Asian and Caucasian patients, regardless of age, gender, study, and treatment. The consistency of these results suggests that Asian and Caucasian patients interpret changes in BPI average pain scores and PGI‐I scores similarly, irrespective of age, gender, study, and treatment.In the present analysis, close associations were found between BPI average pain ratings (raw and percentage change) and PGI‐I scores among Asian and Caucasian patients, as demonstrated by the area under the ROC. The raw levels of change in the BPI average pain scores associated with specific PGI‐I improvement levels could vary based on the baseline pain ratings. Therefore, the percentage change was calculated to adjust the baseline pain rating of each patient; hence, the relationship between the reported change in pain and the patients’ perception of improvement becomes more linear as the mean rating of the BPI average pain change and the PGI‐I categories becomes more consistent.In Asian patients, a percentage change of 40% best correlated with our a priori definition of a CID, namely the PGI‐I category of “much better” or “very much better.” Similarly, a 63% reduction in pain from baseline correlated with the highest degree of improvement on the PGI‐I scale. In Caucasian patients, a percentage change of 40% best correlated with our a priori definition of a CID. Likewise, a 56% reduction in pain from baseline was associated with the highest degree of improvement on the PGI‐I. Also, raw change in BPI average pain scores for “much better” or “very much better” was −3 for the Asian patients and −3 for the Caucasian patients. These results indicate that the percentage and change cut‐off values for CID were similar in Asian and Caucasian patients with OA of the knee or hip. The present analysis results suggest that these values are suitable for use in the interpretation of clinical study results for the design and analysis of future clinical trials of chronic pain treatment. In comparing our results with those of other published studiesThe strength of the present analysis is the consistency observed across all 5 large duloxetine studies conducted in multiple countries with essentially identical measurement instruments and methodology. The common design among the studies eliminates many of the sources of variability, making the association between the change in the BPI average pain scores and PGI‐I scores less likely to have alternative explanations. The present analysis includes patients of different ethnicity (Asian and Caucasian patients). This may provide robust support for the external validity of these results. There are some limitations to the present analysis. The present analysis was performed only in a setting of OA; thus, these findings may not generalize to all chronic pain conditions. Additionally, the PGI‐I score may be affected by patients’ expectations of treatment, and patients’ responses to pain may be influenced by their perception of other improvements in their condition. The present analysis did not examine the effect of these other components, but the consistency of the demonstrated associations across patient populations, age, race, and sex improves the generalizability of our findings. Apart from the concept of symptomatic improvement in a patient's condition, the concept of satisfaction with care could also be used to assess a cut‐off point. However, satisfaction with care has a distinct theoretical concept and has not been included in most pain clinical trials, including those analyzed here.The findings of the present analysis can help design future studies and estimate appropriate sample sizes of pain clinical trials. The presented data also facilitate the comparison of results across Asian and Caucasian patients, which helps to determine the value of a therapy in clinical practice. The findings of this study provide information about the range of BPI average pain scores associated with various degrees of global improvement , irrespective of ethnicity, age, and gender, which can facilitate the evaluation of treatments for chronic pain.In the present analysis of 5 clinical studies of duloxetine in chronic pain due to OA, a consistent relationship between the change in BPI average pain scores and the PGI‐I category was demonstrated in Asian and Caucasian patients, regardless of age, gender, study, and treatment. Moreover, raw and percentage change cut‐off values for CID were similar in Asian and Caucasian patients with OA of the knee or hip. Overall, the present analysis concludes that the ratings for percentage change in BPI average pain by PGI‐I category and the cut‐off for CID were similar for the Asian and Caucasian populations. Applying these findings to future studies may help to standardize the definition of a CID in clinical trials of chronic pain therapies. Use of a standard outcome across chronic pain studies would greatly enhance the comparability, validity, and clinical applicability.All authors are Eli Lilly and Company employees, except for Li Yue. Hiroyuki Enomoto, Shinji Fujikoshi, Levent Alev, Yan Yolanda Cheng, and Vladimir Skljarevski are minor stakeholders. Li Yue and Jianing Wang have no conflicts of interest to declare.


Mastalgia is a common condition that may affect up to two-thirds of patients during the reproductive period. It can be divided into cyclical and noncyclical. It is mostly due to benign causes, but breast cancer should be excluded. It may be associated with a high level of stress and anxiety. Patients need to be assessed fully, breast and general examinations, and investigations such as breast imaging and hormonal assay.This is a prospective study that was done in the breast clinic in the period between February 2019 and July 2019. A total number of 445 patients with mastalgia included were in the study. Patients were examined and evaluated using various imaging modalities.The mean age of the patients was 34 years. Mastalgia was present in 54.2% of our patients, in about 70.1% of our patients it was noncyclical mastalgia. Mastalgia was positively correlated with smoking, oral contraceptive pills, and positive family history of breast cancer  respectively with no correlation with other factors. The type of pain was less in women having early first pregnancy and with the site of the pain showed a positive correlation with the type of pain,  respectively.Mastalgia is a common complaint which may affect most females. It is caused by benign breast disorders in the majority of patients. A systematic approach must be followed for the management of mastalgia. Reassurance, regular exercise, and local analgesics may be very effective initial measures. In severe, intractable cases, hormonal therapy may be used. •Mastalgia is a common condition that may affect up to two-thirds.•It can be divided into cyclical and noncyclical.•It is mostly due to benign causes, but breast cancer should be excluded.•Patients need full assessment by examination, investigations, imaging and hormonal assessments. It is typically felt in the central part and ranges from tension, discomfort, or real pain. It can be divided into cyclical and noncyclical pain, depending on whether the breast pain is occurring in the premenstrual period or not; it usually has a chronic course. This condition is usually due to benign causes, but breast cancer should be excluded because it is the main concern in the majority of women, although it could be associated with premenstrual syndrome, anxiety disorders. Pain in extramammary sources needs to be also excluded like musculoskeletal pain, especially Tietz syndrome or referred pain .When the pain is severe and chronic, it affects the women's daily activities and may cause have a major impact on the mode and the work activities .Mastalgia has been linked to a variety of conditions such as high level of stress and anxiety, depression, chronic myalgia, irritable bowel syndrome, chronic pelvic pain, and some psychiatric disorders which may suggest a psychosomatic base of this type of pain in some patients. Most authors agree that mastalgia has multifactorial pathogenesis ,5.It can be associated with a premenstrual syndrome, which may involve breast pain only or may be a state of generalized body pain and sensation of tension. The cause of the cyclical mastalgia is poorly understood, but it may be due to hormonal effects on the breast tissue or due to a systemic state of water and salts retention in the body .Patients presented with mastalgia need to be assessed fully, including complete personal and family history, breast and general examinations, and the patient may need some investigations such as breast imaging and some of the hormonal assessments .It may be severe that disturb the lifestyle of the patients [Mastalgia is variable in degrees of severity, in some patients it may cause some degree of discomfort or anxiety which mandates performing repeated investigations, and in the other group. patients .The most important step in the management after exclusion of cancer is reassurance ,8,9.Various treatment modalities have been tried for the effective treatment of mastalgia depending on the severity and the chronicity of this condition. Reassurance and work up that exclude cancer are the most important initial workups. Medical treatment has been tried in the form of analgesics, which could be used locally or systemically, which proved to be effective in mild to moderate forms of the complaint. Hormonal treatments like tamoxifen, danazol, and bromocriptine are also used in cases of severe mastalgia and when the first line medical treatment fails ,10.The work of this article has been reported in line with the STROCSS criteria .Aim and objectives: To determine the associated factors that may be correlated with mastalgia.22.1This is a prospective study that was done in the breast clinic in the period between February 2019 and July 2019, we included 445 sequential patients who visited the breast clinic and were complaining from mastalgia.2.2All patients who presented to the surgical unit and complained from breast pain were included in this study, patients complained from other complains other than mastalgia and patients who refused to be included in this study were excluded from this study.2.3Patients presented with mastalgia included in the study, detailed information were taken from, and data recorded using a specially designed questionnaire. Patients underwent breast examination to detect the site of tenderness, lump or lumpiness, any associated nipple retraction or pain. Some patients were evaluated using various imaging modalities such as ultrasound, mammography, and MRI of the breast, and some patients sent for hormonal levels.An informed consent was taken from all the participants to be included in this study.No specific pre-intervention considerations were undertaken.https://www.researchregistry.com/browse-the-registry#home/.In accordance to the World Medical Association's Declaration of Helsinki 2013, the work of this article is registered in the Research Registry, and the unique identifying number is: researchregistry5159.The link to the registration page is: Ethical approval: Ethical committee approval granted from the Directorate of General Health, Scientific Research Division at the April 23, 2019 with reference number 12032019–2.2.4These data analyzed and correlated to various patient characteristics displayed in terms of frequency, mean, median, and standard deviations. The correlation is done using the two-tailed t-tests, chi-square test (χ2), and Fisher's exact test. In the results of the analyses with 95% confidence interval, values p < 0.05 were considered significant. The statistical calculations were done in the Statistical Package for Social Sciences (SPSS 25:00 IBM: USA).3The mean age of the patients who were included in the study was 34 years ranged 9–65 years. Most of the patients were on their menstruating circle (88.3%), have regular menstrual (81.3%), and have a history of lactation (75.3%), were non-smokers (93.9%), non-alcoholic (98.4%), not-coffee drinkers (93.7%), not taking OCCP (95.7%), and have a negative family history of breast cancer (98.0%), as presented in The vast majority of the patients included in this study had menarche at 12 years of age, and the maximum age for menarche was 17 years among our patients, The majority of our patients have noncyclical pain (70.1%) and mostly felt in the left breast (45.8%), see The mastalgia showed significant correlation with smoking status (P < 0.001), history of oral contraceptive pills uses (P 0.009), and family history with breast cancer (P < 0.001) while there was no association with other factors, Analysis of the type of mastalgia, whether cyclical or noncyclical further analyzed and correlated with the patient factors. It showed a significant correlation with the age of the first pregnancy and the site of the pain, The majority of our patients were assessed using the ultrasound, when the diagnosis was not conclusive patients were sent for MRI, mammography was performed for a small number of our patients because most of them were young, The mean age of age of first pregnancy in our patients was 20.9 years, which is considered young when compared with the world data, 4There was a lot of debate regarding whether the type of the pain in mastalgia is a psychoneurotic pain or have a pathological base, some studied concluded that mastalgia should not be more regarded as a psychoneurotic pain because the majority of such patients have either a physiological or a pathological cause .Stress and smoking were negatively associated with mastalgia among our patients. Patients with a positive family history of breast cancer had a higher percentage of noncyclical mastalgia among them, this could be explained by the fear and stress of developing breast cancer, for this reason, and after excluding breast, cancer reassurance should be the first line of management, and it is an effective line in alleviating the breast pain. Studies showed a similar correlation with the same factors ,13,14.In some patients, the pain may settle spontaneously without any form of treatment .A low-fat diet, high carbohydrate, regular exercise, weight reduction, well-fitting bra, and breast support are also included as a first line treatment; some drugs can be used as first-line medications including topical and oral non-steroidal anti-inflammatory preparations. Topical non-steroidal anti-inflammatory preparations are mainly effective when mastalgia is localized, but when involving the whole breast, its efficacy is reduced. Wearing sport brassieres during the day time help to prevent the active breast movements during the daily activities helping to decrease the breast pain because the breasts have weak suspensory ligaments ,7,15.The majority of our patients were not consuming caffeine-containing drinks, which suggest that caffeine intake is not linked to the causation of mastalgia. So women should be no more advised to reduce caffeine intake as one of the treatment lines of mastalgia .A lot of data are available in the literature about the effectiveness of the evening primrose oil in the treatment of mastalgia, but no sufficient evidence is present about the effectiveness of such treatment in the majority of the patients. Vitamin E preparations are also of low value in the treatment of mastalgia in most patients but may be of value in women with cyclical mastalgia who are taking hormonal therapy as well ,16.If the first line therapy is not effective, other modalities of treatments are tried like the hormonal therapy, but such treatment is only indicated in the refractory cases. This hormonal therapy may include anti-prolactin drugs such as bromocriptine, antiestrogens such as tamoxifen and androgen agonists such as danazol. This hormonal therapy is usually given to patients with severe mastalgia, which is not responding to other modalities of treatment. Most patients tend to prefer bromocriptine because of lower side effects and a significant reduction in the level of prolactin. Both cyclical and non-cyclical mastalgia have an approximate response rate ,17,18.Danazol showed that it an effective drug in the management of both cyclical and non-cyclical mastalgia .Some newer agents may be used, especially in the intractable cases; these agents may include lisuride maleate .Cyclical mastalgia may be considered as an independent risk factor for the development of breast cancer, but further studies are required with solid evidence and further evaluation. In our study, most of the involved patients were menstruating and we didn't find any significant correlation between the menstrual status and mastalgia .Nipple discharge was present in 18.87% of our patients, we didn't find any significant correlation between mastalgia and nipple discharge, some authors correlated nipple discharge with mastalgia especially the non-cyclical one .In 4% of the patients in our study, the pain had musculoskeletal origin being referred either from the shoulder or from the neck, in these patients the pain intensity was significantly reduced with the analgesics and the local steroid injections. All doctors should be aware of this musculoskeletal type of pain and should be differentiated from mastalgia, especially the noncyclical one for effective management .Intractable mastalgia is seen in about 25% of the noncyclical type and 5% of the cyclical one, in such patients, all the treatment modalities will fail to alleviate the pain. Soma authors had tried a surgical intervention in such groups either with quadrantectomy or even mastectomy with breast implants. Most patients resolved with the mastectomy but complications reported with the use of breast implants, so most authors don't recommend surgery, but when the pain is very severe and intractable for years such treatment can be offered in a very selected group of patients .Goserelin is an effective drug in the management of severe mastalgia, although it has many side effects but provides a significant short term relief of pain .The limitation of this study is that longer term follow up period is required and the population based study may be required. Future studies should include the different types of pain characters, and its association with various physiological breast changes.5Mastalgia is a very common complain among patients who have breast complains, the most important step in the management is to exclude breast cancer. The management should include a systematic approach starting from the detailed history and breast examination, imaging assessment and in some patients histopathological evaluation is required. The majority respond to life style modifications and analgesics, hormonal therapy may be required in some patients.NA.No source of funding other than the authors.Study design, data collection and analysis, writing and final approval of the manuscript: Dr Ayad Ahmad Mohammed.Researchregistry5159.N/A.Dr Ayad Ahmad Mohammed.The author was only financial supporter of the study.No conflicts of interest present.


Meniscus repair is a challenge for a practitioner, as an injured meniscus can lead to osteoarthritic joint changes with a greatly disabling outcome. Platelet-rich plasma has been regarded as a promising therapy to help induce healing. The purpose of the study is to clinically assess the effectiveness of PRP treatment in adolescents with meniscal lesions.  This retrospective study analyzed 30 patients with meniscal tears, aged 12 to 17 years, who had documented MRI meniscal lesion and persistent knee pain. In order to evaluate the outcome, the Lysholm knee scoring scale and numerical rating scale were used before injection and 3 months after treatment.  Patients had a mean age of 13.93 years, 70% girls and 30% boys. The most affected was the medial meniscus. The mean value before injection on the numerical rating scale (NRS) of pain was 7.73, after the treatment being of 2.0. After treatment, 76.7% of the patients had “excellent” and “good” outcomes, while before injection, just 3% of the patients had a “good” score.  Platelet-rich plasma treatment can be effective in improving the clinical outcomes of adolescent patients with meniscus tears, for whom conservative management and physical therapy have failed to achieve pain relief. Adolescent participation in athletics increased lately and, with it, an inflation of sport-related injuries such as meniscal tears, leading to possible unfavorable effects on the growing skeleton in the long term .The importance of the menisci is highlighted after complete or partial meniscectomies that may lead to osteoarthritic and degenerative changes, as menisci are structures that are critical to shock absorption, load sharing, and stability within the joint , 3. Fromβ1 (TGF-β1), fibroblast growth factor-2 (FGF-2), insulin-like growth factor 1 (IGF-1), epidermal growth factor, platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). The regenerative effects of these growth factors, such as cell proliferation, migration, angiogenesis, and extracellular matrix production, had been demonstrated both in in vivo and in vitro models [Extra-articular ligaments heal by the following precise steps: after bleeding, a fibrin-platelet clot forms at the lesion site and fills the gap between the tissue ends, forming a scaffold for the surrounding cells . In intro models –18. In to models .The controversy about the effectiveness of biologics in orthopedics led to the need for standardizing the outcome measurements. Clinical outcome scores have been extensively used to evaluate patients after a vast array of procedures from cartilage restoration to ligament reconstructions .In the revised Lysholm scale, scores are categorized as excellent (95–100), good (84–94), fair (65–83), and poor (<64) . Pain isThe purpose of the study is to clinically assess the effectiveness of PRP treatment in adolescents with meniscal lesions.A retrospective study was conducted on 30 patients with meniscal tears that were admitted and treated between December 2015 and December 2018. The study was conducted with the approval of the hospital's ethics committee. The inclusion criteria were adolescent patients, age ranging from 12 to 17 years, patients who had documented MRI meniscal lesion grade II according to Reicher et al. [The same intra-articular injection technique and PRP system were used for each patient. After injection, all patients underwent the same recovery protocol; no cast or immobilization was applied. They were not allowed to bear full weight for one week and advised to limit their physical activities for one month. For the management of post injection pain, patients were not allowed to take NSAID. This recommendation was maintained for at least 6 months as NSAID interfere with platelet functions .t-test.In order to evaluate the outcome, for each patient, the Lysholm knee scoring scale was conducted by the orthopedic surgeon before injection and 3 months after treatment. Also, before and after treatment, patients were asked to rate their pain on the numeric rating scale. Statistical analysis was performed with Statistical Package for the Social Sciences (SPSS) and Microsoft Office Excel using descriptive statistics and comparing means with the Patients had a mean age of 13.93 years, 70% girls and 30% boys. Regarding the site of injury, the right knee was the most affected (56.66%). The most frequent location for tears was in the medial meniscus (70%). The amount of time from the onset of pain until the PRP treatment ranged from 30 days to 770 days, with a mean of 235 days .The mean value on the NRS of pain was 7.73, before injection, after the treatment being of 2.0. After treatment, 76.7% of the patients had “excellent” and “good” outcomes, according to the Lysholm score, while before injection, just 3% of the patients had a “good” score. Comparing the mean scores for the pain scale and Lysholm score before and after injection, an improvement was observed in the mean values, which is statistically significant .p = 0.4), while the score after the treatment was 89.81 for girls and 86 for boys. An improvement of the symptoms in females compared to male patients was registered, but not statistically significant (p = 0.64), mainly because the number of male patients included in the study was too small (There was no difference between boys and girls regarding the pre and post injection scores. The Lysholm score had a high standard deviation (SD), meaning that the values are widespread around the mean. Concerning the Lysholm score before injection, girls had a mean of 50.38 and males 57.1 . An improvement was also observed in the Lysholm score (96 vs. 85), but it was not statistically significant  or worsening of their symptoms .Platelet-rich plasma treatment can be effective in improving the clinical outcomes of adolescent patients with intramural meniscus tears, for whom conservative management with physical therapy has failed to achieve pain relief.


Total knee arthroplasty (TKA) is an established and successful surgical procedure which is the major treatment for degenerative knee joint diseases. A novel technique to address posterior knee joint pain is the infiltration of local anesthetic between the interspace between the popliteal artery and capsule of the knee (IPACK). The goal of this randomized clinical trial was to assess the efficacy and safety of adding IPACK to adductor canal block (ACB) after TKA.This was a prospectively randomized trial that investigated the effectiveness and safety of the IPACK after TKA. Approval from Clinical Studies Ethical Committee in Qilu Hospital of Shandong University was obtained. The inclusion criteria were adult patients undergoing primary unilateral TKA and American Society of Anesthesiologists grade 1 or 2 with normal cognitive function. The patients were randomized to 1 of 2 treatment options: ACB-alone group and ACB + IPACK group. The primary outcome was the total morphine consumption during postoperative 24 hours. Secondary outcomes included postoperative pain score, time to first and total dosage of rescue morphine in postoperative 48 hours, early and late postoperative period (from postoperative day 0–3 months follow-up) performance-based test . Postoperative nausea and vomiting, length of hospital stay, patient satisfaction, and other adverse events were also evaluated.It was hypothesized that when combined with a control group, the IPACK block would result in a lower morphine consumption and pain score after TKA.This study protocol was registered in Research Registry (researchregistry5765). Perioperative pain control has direct influence on postoperative recovery and surgical outcome. An appropriate perioperative analgesic protocol could relieve postoperative pain and allow functional exercising, leading to early rehabilitation.Total knee arthroplasty (TKA) is an established and successful surgical procedure which is the major treatment for degenerative knee joint diseases. With the popularity and promotion of TKA, increasing numbers of patients with degenerative knee diseases are undergoing this surgery to restore knee function and mobility, as well as to improve quality of life.–8 Recently, adductor canal block (ACB) has been demonstrated to be an effective alternative to the femoral nerve block, providing similar analgesic efficacy while sparing the motor strength significantly. Both ACB and FNB provide analgesia primarily to the anterior medial part of the knee, and as a result, TKA patients typically require supplemental multimodal analgesia, including opiates, to address posterior joint pain.,9Femoral nerve block (FNB) is one of the most commonly used pain-relief methods, which has been proven to be effective on relieving the pain, reducing the usage of opioid painkiller, and shortening the hospital stays. Moreover, FNB is regard as the gold standard for postoperative analgesia after TKA by some surgeons. However, FNB may lead to postoperative quadriceps weakness, which not only limits the patients’ ambulation and early physical rehabilitation, but also increases the risk of falling. These deficiencies make the rehabilitation results unsatisfactory. Indeed, a cadaveric study demonstrated that an IPACK injection surrounded the middle genicular artery with injectate, supporting the hypothesis that local anesthetic infiltration surrounding the articular sensory nerves near the middle genicular artery is a potential mechanism of analgesia for the IPACK. This study also showed potential for the injectate to contact the tibial and commonperoneal nerves, so an IPACK block could potentially result in sensory and motor deficits below the knee.A novel technique to address posterior knee joint pain is the infiltration of local anesthetic between the interspace between the popliteal artery and capsule of the knee (IPACK). IPACK provides analgesia to the posterior compartment of the knee without compromising foot strength.–14 As such, the goal of this randomized clinical trial was to assess the efficacy and safety of adding IPACK to ACB after TKA. It was hypothesized that when combined with a control group, the IPACK block would result in a lower morphine consumption and pain score after TKA.However, studies evaluating the effect of IPACK block on postoperative knee pain after TKA are lacking.22.1This was a prospectively randomized trial that investigated the effectiveness and safety of the IPACK after TKA. Approval from Clinical Studies Ethical Committee in Qilu Hospital of Shandong University was obtained (DSA793002). This study has been published at the Research Registry (researchregistry5765). We followed the Consolidated Standards of Reporting Trials (CONSORT) guidelines for reporting randomized trials and provided a CONSORT flow diagram Fig. .2.2The inclusion criteria were adult patients undergoing primary unilateral TKA and American Society of Anesthesiologists grade 1 or 2 with normal cognitive function. The exclusion criteria were the following: patients unwilling to participate, poorly controlled diabetes, history of inflammatory arthritis, nonambulatory/bed ridden patients, known allergy to the anesthetic drugs, history of bleeding disorder, history of arrhythmia or seizures, sepsis, and pre-existing lower extremity neurological abnormality.2.3The patients were randomized to 1 of 2 treatment options: ACB-alone group and ACB + IPACK group. Randomization was performed without any stratification. Randomization listings were prepared with a probability of 0.4 to 0.6 and after that, randomization letters were printed according to the results of the randomization. After the patient had given consent, a member of the in-hospital clinical study center chose 1 of the 2 letters and the patient was assigned to 1 group. Patients, surgeons, anesthesiologists, nurses, and research assistants collecting data were blinded to group allocation.2.4The patients were admitted to the operating room without any premedication. Spinal anesthesia was administered by means of a 22-gauge spinal needle, consisting of 15 mg (3 mL) of 0.5% spinal bupivacaine to each patient after both ACB and ACB + IPACK. All operations were performed by the same surgical team using a similar technique.For patients in the ACB-alone and ACB + IPACK groups, an ACB was performed in the preoperative block area by the regional anesthesia team prior to surgery. This team included an attending anesthesiologist who performed or oversaw the ACB. The ACB was performed under ultrasound guidance at the midlevel of the thigh (at the midpoint between the anterior superior iliac spine and the superior pole of the patella) using 15 mL of 0.5% bupivacaine. For patients in the ACB + IPACK group, IPACK blocks were performed under ultrasound guidance with a 5 to 2 MHz curvilinear transducer using a 22 G 4-in. Chiba-type spinal needle. The anesthesiologist identified the popliteal artery, in a short-axis view, at the popliteal crease and moved cephalad just beyond the femoral condyles, at the level where the condyles merge with the shaft of the femur. The tibial and peroneal nerves were visualized superficial to the popliteal artery. After identifying the space between the femur and popliteal artery, the needle was advanced in-plane from medial to lateral. The tip was positioned at the middle of the femur and near the lateral border near the periosteum. Subsequently, 5 to 10 mL of local anesthetic was injected to ensure adequate spread to the lateral end of the femur. On withdrawing the needle, the anesthesiologist further injected the rest of the 25 mL of 0.25% bupivacaine along the femur, infiltrating 5 mL incrementally in the area between the artery and femur, and finishing at the medial end of the femur.2.5All subjects underwent a standard preoperative and postoperative multimodal pain management regimen. Preoperative medications, which included acetaminophen, oxycodone, celecoxib, and gabapentin, were given in the preoperative area 1 hour prior to surgery. Postoperative medications included acetaminophen, ketorolac followed by celecoxib (for 3 months), gabapentin (standing order for 10 days), oral opioids (as needed), and intravenous hydromorphone for breakthrough pain.2.6The primary outcome was the total morphine consumption during postoperative 24 hours. Secondary outcomes included postoperative pain score, time to first and total dosage of rescue morphine in postoperative 48 hours, early and late postoperative period (from postoperative day 0–3 months follow-up) performance-based test . Postoperative nausea and vomiting, length of hospital stay, patient satisfaction, and other adverse events were also evaluated.2.7α value of 0.05 and a power of 85%. It was estimated that the attrition rate due to canceled surgery or reasons of late patient ineligibility could be up to 20% and, therefore, to account for this, the final sample size selected was n = 94 (47 per group).The sample size calculation was based on a pilot study that we conducted on 16 patients (whose data were not included in the present study). In this prior study, the mean difference and standard deviation of the pain scores 24 hours after the operation between the ACB and ACB + IPACK groups were 0.40 and 0.19, respectively. From this, it was determined that 39 subjects would be required to reach an 2.8P value of <.05 was considered statistically significant.Data were analyzed using the statistical software package SPSS version 25.0 . Continuous variables were described as the mean ± standard deviation, and differences between groups were analyzed using a series of one-way analysis of variance (ANOVA) with Bonferroni post-hoc test, while differences between groups over time were analyzed using multi-way ANOVA with Bonferroni post-hoc test. Categorical variables were described as the number (%), and were analyzed by Fisher exact test. A 3As clinicians improve healthcare, a common goal is to maintain quality measures while reducing hospital length of stay. Advancements in postoperative regional analgesia, specifically the introduction of the ACB, have been pivotal in optimizing care for patients undergoing TKA. Although ACB is effective, it primarily addresses anterior knee pain, and patients often need supplemental analgesia to address posterior knee pain. The posterior knee capsule is innervated by the terminal branches, which ramify from the popliteal plexus mainly formed by the contribution of the tibial and posterior branch of the obturator nerves. A novel technique to address posterior knee joint pain is the infiltration of local anesthetic between the IPACK. IPACK provides analgesia to the posterior compartment of the knee without compromising foot strength. The goal of this randomized clinical trial was to assess the efficacy and safety of IPACK after TKA.Conceptualization: Fengying Ma.Data curation: Lejun Zhang.Formal analysis: Lejun Zhang.Funding acquisition: Zhongxiao Cong.Investigation: Zhongxiao Cong, Lejun Zhang.Methodology: Zhongxiao Cong.Resources: Zhongxiao Cong.Software: Lejun Zhang.Supervision: Fengying Ma.Validation: Fengying Ma.Visualization: Fengying Ma.Writing – original draft: Zhongxiao Cong, Lejun Zhang.Writing – review & editing: Fengying Ma.


Meanwhile, although the risk of infection  may be comparable between the two modalities,2 the risk of endocarditis should be expected to be nearly nonexistent with the S-ICD given the avoidance of vascular access. However, the cost of the S-ICD does come at a small premium and there are also the additional concerns of general anesthesia and hospitalization for postoperative pain control adding to the perceived expenditures, which may act as a barrier to adoption in some centers.Subcutaneous implantable cardioverter-defibrillators (ICDs) (S-ICDs) have slowly been gaining a reputation as a cardiac implantable electronic device option that imparts a lower surgical risk, particularly among younger patients requiring ventricular fibrillation therapy or those patients with multiple comorbid illnesses who are at high risk for adverse outcomes if given transvenous systems. Though we have not yet seen a landmark randomized trial of comparison, existing registry and prospective cohort studies do favorThe Journal of Innovations in Cardiac Rhythm Management, the results of a small series of patients at Riverside Hospital in Columbus, Ohio are reported. Among patients (n = 24) who underwent S-ICD, half of whom were sent home on the same day as device implantation (n = 13), Swinning et al.,3 found no specific increased risk. A reasonable health care system cost savings of $1,664.48 per patient was reaped with the protocol of same-day early discharge after S-ICD implantation. In such a study, specific details matter, with patients being excluded if they lived more than 30 miles away from an emergency room, if they did not have a driver who could stay overnight with them at home, or if their procedure was completed after 1:00 pm. Based on a heavy male bias , one could suspect that sex was also an exclusion or played a role in the perceived pain tolerance and stability of the patient that made them eligible for same-day discharge, although the sample size is too small to draw definitive conclusions of this kind.In this issue of 4 or by an individual’s pain tolerance, which is driven both by psychological5 and physiological6 factors. Longer-acting and carefully placed local anesthesia is key to better pain outcomes during the first six to 12 hours postsurgery. Swinning et al. do not mention a specific protocol for adjunctive therapy such as the use of nonsteroidal anti-inflammatory drugs like ketorolac or ibuprofen on a scheduled basis, which could help to alleviate late inflammatory pain effects. Also, it would be useful to assess the impact of interrupted direct oral anticoagulants/novel oral anticoagulants or oral anticoagulation and antiplatelet therapy on the decision to pursue same-day discharge as well as any impact that may occur on the rate of presentation of delayed hematoma requiring evaluation or management.In our experience, the most likely issue to appear after S-ICD implantation is local site pain, which can be affected by patient size or body mass index7 Still, the authors’ use of telemedicine visits for wound checks and patient assessments as an element of routine care following S-ICD placement or to triage issues that arose in the early postoperative period among same-day discharge patients is to be commended. Both this study and the data we are now gathering from efforts to continue patient care during the ongoing COVID-19 pandemic support the potential for greater telemedicine adoption in medicine, potentially leading to an earlier diagnosis of problems and subsequent reductions in disease severity or complications. More specifically, in the area of cardiac electrophysiology, this study clearly marks another step toward alleviating hospital stay expenses and mobility limitations together with the other research available on same-day discharge after cardiac resynchronization therapy device implantation,8 laser lead extraction , atrial fibrillation ablation,9 and left atrial appendage closure.10It is important to note this study was performed before the coronavirus disease 2019 (COVID-19) pandemic and the resultant widespread adoption of telemedicine visits for clinic, consults, and other meetings to avoid risking exposure of both patients and providers alike to the virus.


The efficacy of preemptive analgesia in managing postoperative pain remains controversial. The aim of this study was to compare the efficacy of intravenous (IV) acetaminophen administered before or immediately after the surgical extraction of an impacted mandibular third molar. This prospective randomized clinical trial included 120 patients. The patients were assigned to one of three groups: the preoperative-treatment group (pre-group), which received 1000 mg of IV acetaminophen 20 min before surgery; the postoperative-treatment group (post-group), which received 1000 mg of IV acetaminophen after surgery; the no-treatment group (control-group), which did not receive any analgesic. Rescue analgesic (60 mg loxoprofen) was issued to each patient, with instructions on self-administration if needed. For the rescue medication usage, the time of first loxoprofen usage and the total amount of loxoprofen consumption were obtained for a 17-hour period after surgery. We measured pain using the visual analogue scale at 1 hour and at 2, 3, 4, 5, and 15 hours after surgery. There was no significant difference in pain level among the three groups at any time interval. However, the pre-group demonstrated significantly lower rescue analgesic consumption and longer time until initial administration. Administration of IV acetaminophen before third molar surgery provides more effective pain control than postoperative administration and no treatment. Key words:Preemptive analgesia, acetaminophen, impacted third molar, pain relief, randomized controlled trial. The extraction of wisdom teeth, or third molars, is the most common procedure in the field of oral and maxillofacial surgery. The removal of an impacted lower third molar is particularly invasive and often associated with postoperative pain, swelling, and trismus, which frustrates patients . EffectiPreemptive analgesia is one of the many strategies for pain management. This approach involves managing pain before its onset to minimize postoperative pain by interrupting afferent input. Thus, the most effective preemptive agents for reducing central sensitization are analgesics that act on pain due to injuries caused by incisions and the associated inflammation .The efficacy of preemptive analgesia in managing postoperative pain remains controversial. Previous randomized control trials have concluded that preemptive analgesia improves postoperative pain ,4. HowevAcetaminophen has both central and peripheral effects, similar to nonsteroidal anti-inflammatory drugs (NSAIDs). Acetaminophen acts to inhibit the synthesis of prostaglandin  and blocTo the best of our knowledge, this is the first study investigating preemptive intravenous (IV) acetaminophen as a method to reduce postoperative pain and evaluating the use of rescue analgesics following lower third molar surgery. The aim of this study was to compare the efficacy of rescue IV acetaminophen administered before or immediately after the surgical extraction of an impacted mandibular third molar in three groups of patients: those who received preemptive acetaminophen, postoperative acetaminophen, or no analgesic.Our study was designed to evaluate preoperative IV acetaminophen in a prospective, single-blind, randomized, clinical trial. Our hypothesis was that preemptive acetaminophen is superior to either acetaminophen used postoperatively or no analgesic. Our outcome was patient-reported postoperative pain and the usage of rescue analgesics used by patients following lower third molar surgery.- PatientsThis randomized, single-blind study was performed on patients undergoing single mandibular third molar surgery between September 2017 and May 2019 in the Department of Dentistry and Oral Surgery at the Uji Takeda Hospital. A total of 120 patients between 20 and 68 years old were enrolled according to the Consolidated Standards of Reporting Trials (CONSORT) protocol . A copy Randomization was based on the opaque, sealed-envelope technique. A total of 120 identical opaque sealed envelopes labeled with a serial number, each containing the name of one of the groups (with 40 envelopes per group), which was determined in advance by the function “randbetween” in Microsoft Excel version 2016 , were prepared before the initiation of the study. The resident dentist, who was not involved in patient care, selected an envelope and directed the pharmacy to prepare the analgesia medications. This trial was single-blind; i.e., only patients were blinded to the treatment groups.- Surgical procedureAll surgeries for this study were performed by a single surgeon-assistant pair. After confirming the patient’s fasting status, IV access was established using a 22-gauge Intracath  catheter. Routine noninvasive blood pressure, heart rate, and peripheral oxygen saturation monitors were connected to the patient. Oxygen was delivered via nasal cannula at 1 L/min. Sedation medication and local anesthesia were administered by the surgeon prior to the procedure. Sedation was performed using 0.075 mg/kg of midazolam as a single IV bolus. Local anesthesia was performed by blocking the inferior alveolar, lingual, and buccal nerves with two 1.8-mL capsules of 2% lidocaine with 1:80,000 epinephrine . To standardize the resulting surgical trauma, the surgery was performed using the classic full-flap technique, with bone removal and tooth sectioning based on the condition of the third molar. Suturing was performed using 4-0 silk. The duration of the operation  was recorded.- Outcome variablesThe primary outcome variable was self-reported postoperative pain. Patients were instructed to complete a report every hour for the first 5 to 15 hours after surgery. We used the visual analogue scale (VAS) for assessment of postoperative pain, which ranges from “no pain” to “pain that could not be more severe.” Patients were instructed to mark a point between these extremes that represented their pain levels. The secondary outcome variable was the time at which the initial dose of the rescue medication was taken and the subsequent frequency of administration. Additionally, patients were instructed to record the number of pills taken and the time of analgesia use for 17 hours after surgery. We collected adverse events data to evaluate the safety of the analgesic regimen.- Statistical methodsp value <0.05 was considered statistically significant for all analyses. Data are presented as mean values and standard deviation. The demographic data of the study groups were compared using the chi-squared (χ2) test for qualitative variables and one-way analysis of variance for quantitative variables. Differences in variables, such as surgery duration, VAS pain scores at each of the fixed time intervals, the time until the initial intake of rescue analgesic, and total analgesic consumption between groups, were analyzed using the Kruskal-Wallis test. If the Kruskal-Wallis test indicated a statistically significant difference between groups for any given variable, the Mann-Whitney U test with Bonferroni correction was applied to identify the group that demonstrated the statistical difference. The proportion of subjects requiring the rescue medicine was compared between the study groups using the log-rank test. Cox proportional hazard models were used to further analyze the results.Using G*Power version 3.0.10 for Windows , it was determined that 34 patients per group were needed to achieve 80% power with 95% confidence. Forty patients were enrolled in each group to account for possible dropouts. Statistical analysis was performed using SPSS version 26 for Windows  and the R package version 3.4.1 for Windows . A - Demographic and clinical dataA total of 120 patients were recruited to participate in this study, and 120 patients (38 men and 82 women) between 20 and 68 years old (32.5 ± 11.9 years) completed the study and filled out all required reports. No data were missing. A flowchart of patient participation in this study is shown in Fig. - Analysis of VASThe pre-group and the post-group exhibited peak pain elevation 2 hours after the surgical procedure , and the no-group exhibited an elevated pain peak 3 hours after the surgical procedure (3.38 ± 2.14 hours). There was no significant difference in pain level at each fixed time interval among the three groups .- Time of initial intake of rescue medicationp = 0.001). Further analysis revealed significant differences between the pre-group and the no-group (p = 0.003) and between the post-group and the no-group (p = 0.016). There was no significant difference between the pre-group and the post-group (p = 0.774)  .In addition, the proportion of subjects not requiring rescue analgesic was significantly higher in the pre-group throughout the observation period Fig. . Further- Amount of rescue analgesic consumptionp = 0.01). Further analysis revealed a significant difference between the pre-group and the no-group (p = 0.014). There were no significant differences between the pre-group and the post-group (p = 0.256) or between the post-group and the no-group (p = 0.333)  .- Adverse eventsThere were no complications associated with the surgical procedure. There were no serious adverse events, such as nausea or vomiting, due to pharmacological interventions in any of the groups.Several clinical trials have examined different approaches to minimize pain and curtail the need for additional analgesics to reduce the incidence of adverse effects following third molar extractions. Preemptive analgesia is one such approach and has been studied extensively. A relationship exists between operative tissue damage and intense postoperative pain, both acute and chronic, as a result of tissue damage, which activates nociceptors . The preet al. (Previous studies that have attempted to assess the efficacy of preemptive analgesia in patients undergoing oral surgery used protocols in which the outcome of preoperative administration was only compared against outcomes of either preoperative placebo administration  or postoet al. , studiesPrevious clinical trials on preemptive analgesia typically used NSAIDs as analgesics . No prevet al. (In this study, we found no differences in treatment outcomes among patients who received preemptive acetaminophen analgesia, postoperative acetaminophen analgesia, and no treatment, as measured by the VAS. Ethically, all analgesic evaluations must ensure patient protection; thus, all our patients had access to rescue medication for use according to their pain scale. All patients reported sTable postoperative pain, resulting in no differences in the VAS scores among the patients. Our aim was to assess the effect of a single IV administration of acetaminophen. Patients could take rescue medicine to address their perception of pain after surgery. If rescue medicine intake was limited, different results may have been attained. Moreover, Ong et al.  suggest The first 12 hours after surgical extraction of an impacted lower third molar are considered to be the worst in terms of perceived pain . If theret al. (Studies that have investigated the use of preemptive acetaminophen during other surgeries have demonstrated similar results. Koteswara et al.  recruiteet al. (Kharouba et al.  recruiteet al. (Khalili et al.  recruitein vitro and appears to have very little anti-inflammatory activity, although some reduction of tissue swelling after dental surgery has been reported (Although there is evidence that the serotonergic pain pathway is acted on by acetaminophen, the full mechanism of action is unclear. It is understood that acetaminophen is very efficient after IV administration, primarily because of its ability to cross the blood–brain barrier . Interfereported .One of the major advantages of acetaminophen is the low frequency of side effects compared with other non-opioid analgesics used for the treatment of postoperative pain . SystemaA major limitation of this study is the short survey period after surgery. Efficacy should therefore be tested using a longer survey period. Another limitation of this study is the lack of objective assessment of pain relief. We did not find differences in pain relief, as measured by the self-reported VAS, among the three groups despite the patients knowing how to fill the report. If different assessments, such as the face rating scale or verbal rating scale, were used at the same time, a different result may have been attained.In conclusion, we examined the effect of preemptive acetaminophen on postoperative pain and rescue analgesic use in patients who underwent lower third molar surgery. There was no significant difference in postoperative pain intensity among the three treatment groups. However, the total consumption of rescue analgesics was significantly lower and the time until initial rescue analgesic use was longer in the preemptive IV acetaminophen group. This study makes a novel contribution to the literature by proposing the role of preoperative IV acetaminophen in pain management following third molar surgery under sedation.


Acute pain management after craniotomy can be challenging. Previous studies have shown inadequate pain control following the procedure. Oral medication can sometimes be delayed by postoperative nausea, and use of anesthetics may impair the assessment of brain function. We conducted this prospective study to evaluate the effect of acupuncture at the P6 acupoint on postoperative pain, nausea, and vomiting in patients undergoing craniotomy.  The authors conducted a randomized, placebo-controlled trial among 120 patients scheduled for craniotomy under general anesthesia. 120 patients were randomly assigned into an acupuncture group or a sham acupuncture group. All patients received standardized anesthesia and analgesia treatment. Acupuncture was executed in the recovery room after surgery. For the acupuncture group, the P6 points on each wrist were punctured perpendicularly to a depth of 20 mm. Needles were retained for 30 min and stimulated every 10 min to maintain the De-Qi sensation. For the sham acupuncture group, sham points on each wrist were punctured perpendicularly to a depth of 5 mm. Needles were retained for 30 min with no stimulation during the duration. The postoperative pain scores, PONV, and dose of tramadol were assessed 24 h, 48 h, and 72 h after surgery. P > 0.05). The VAS pain score of the acupuncture group was lower than that of the sham acupuncture group, and this difference was statistically significant (P=0.002). There was no difference in pain scores between the two groups during 0–24 h and 48–72 h (P > 0.05). The incidence of vomiting in the acupuncture group was lower than that in the sham acupuncture group during the 0–24 h period . There was no difference in vomiting, however, during the 24–72 h period (P > 0.05). No significant differences were found in the degree of nausea and the dose of tramadol between the two groups at either time point in the acupuncture group and sham acupuncture group.  A total of 117 patients completed the study. There was no statistically significant difference in baseline data between the two groups ( The use of acupuncture at the P6 acupoint in neurosurgery patients did result in significantly lower pain scores and reduction in the incidence of vomiting after craniotomy. There were no significant side effects. Acupuncture at the P6 acupoint was well tolerated and safe in this patient population. A review paper has analyzed publications in the international literature regarding the problem of acute postoperative pain in neurosurgical patients who have undergone craniotomy. This review indicated that the problem of acute postoperative pain in patients after craniotomy has been previously underestimated. It had been mistakenly thought that these patients do not experience any pain in the early postoperative period. Results of recent studies have shown that up to 80% of these patients may in fact experience acute mild to severe pain . PostopePain management after craniotomy is a clinical problem. The main challenge is that analgesic therapy may interfere with nervous system function and postoperative evaluation. Numerous studies have shown that patients in the neurocritical care (NCC) unit experience inadequate pain control , 5. OptiMultimodal analgesia is advocated currently for postoperative pain. There are two aspects of multimodal analgesia. (1) Balanced anesthesia affects the local anesthetics of the scalp, opioid, and nonopioid analgesics. (2) Nonpharmacologic treatments include distractibility, massage therapy, transcutaneous electrical nerve stimulation therapy, and acupuncture.Acupuncture is a traditional Chinese medical technique that has been extensively used as a nonpharmacological analgesic therapy since being developed 2500 years ago. Over the last decade, many clinical studies have focused on acupuncture in the treatment of postoperative pain. For example, a systematic review suggested that acupuncture can relieve acute postoperative pain after back surgery . AnotherStimulation of specific points, by using needles or electrodes, releases neurochemical substrates that may block the incoming pain information. Acupuncture can raise the pain threshold. It also reduces pain intensity . The P6 The patient's awareness assessment will not be affected because acupuncture is a nonsedating treatment. The aim of this controlled, randomized, single-blind study was to evaluate the effect of acupuncture at the P6 acupoint on postoperative pain following craniotomy. We hypothesized that acupuncture at the P6 acupoint may reduce the postoperative pain experienced by patients.Our study protocol was published in Trails in 2013. We followed the methods of Lv et al. . This raAll participants gave their written informed consent before being enrolled in this study. In this prospective randomized controlled trial, all cases were from the Department of Neurosurgery, West China Hospital, Sichuan University. Patients were enrolled in the study from October 2014 to September 2017. A total of 120 patients were recruited. SAS 11.0 statistical software was used to design the random number. Patients were randomly assigned into either an acupuncture group or a sham acupuncture group. All the subjects involved were unaware to which group they had been assigned, as was the doctor who observed the postoperative pain and other outcomes.Patients who fulfilled the following conditions were included: (1) scheduled for neurosurgery requiring opening of the cranium and dura; (2) aged between 18 and 70 years old; (3) the American Society of Anesthesiologists (ASA) physical status classification of I or II; (4) undergoing general anesthesia; (5) no history of PONV or motion sickness; (6) no use of antiemetics and analgesia 24 hours before surgery; (7) willing to participate; (8) no experience with acupuncture; and (9) having signed an informed consent form.Participants that met any of the following criteria were excluded: (1) pain 24 hours before surgery; (2) pregnant or lactating women; (3) drug or alcohol abusers; (4) recipients of chemotherapy or radiation therapy during the previous 7 days; (5) having a cardiac pacemaker fitted; (6) menstruating phase of the menstrual cycle; (7) refusal to accept acupuncture treatment; (8) mental disorder; (9) history of epilepsy and still taking an antiepileptic medicine; (10) unconscious before the surgery; (11) cannot normally communicate; (12) undergoing ventricle or brainstem surgery; (13) cerebral perfusion pressure (CPP) of less than 50 mmHg or greater than 150 mmHg; (14) poorly controlled diabetes mellitus (fasting plasma glucose greater than 12 mmol/L); (15) bleeding disorders (hemophilia or afibrinogenemia); and (16) serious systemic disease (AIDS or sepsis).Participants who met any of the following criteria were withdrawn from the study: (1) death; (2) waking more than 2 hours after surgery; (3) trachea intubation; (4) persistent coma; (5) cognitive impairment; and (6) further surgery or transfer to the ICU if necessary for the aggravation of the disease. Patients who were withdrawn were not replaced.2 were routinely monitored. Induction of anesthesia was achieved with midazolam 0.05 mg/kg, sufentanil 0.3 μg/kg, atracurium 0.15 mg/kg, and propofol 2 mg/kg. When endotracheal intubation and gastrointestinal decompression with either an orogastric or nasogastric tube were undertaken, the anesthesia was maintained with 50% nitrous oxide and 3% sevoflurane. The concentration of sevoflurane was adjusted according to BIS and the vital signs; if hypotension occurred and the BIS was low, the sevoflurane dosage was decreased. After the operation had commenced, participants were given sufentanil 0.2 μg/kg and atracurium 0.1 mg/kg intermittently. 30 minutes prior to the end of the operation, the patients were treated with prophylactic antiemetic drugs: ondansetron injection 8 mg according to the advice of doctors. After surgery, patients were continually monitored in the postanesthesia care unit (PACU) with continued ventilator support. The tracheal tube was removed after the patients woke. The time from the start of anesthesia induction to the time of removal of the tube was recorded. Patients who then met the criteria  were sent back to the ward.All patients underwent general anesthesia with endotracheal intubation. Blood pressure, heart rate, pulse oximetry, and end tidal COAfter the participants returned to the neurosurgical ward, the doctor decided whether to give pain medication according to the degree of the patient's pain. The patient was given a 10 mg intramuscular injection of tramadol if necessary, and the degree of postoperative pain was recorded when the patient was given the drug.Randomization and blinding SAS 11.0 statistical software was used to design the random number of patients for the study. The included participants were randomly enrolled by sealed envelope and assigned to the acupuncture group or the sham acupuncture group. Patient allocations were performed by a clinical assistant trained in institutional review board policies. Patients in the two acupuncture groups were unaware to which acupuncture group they were assigned. The outcome assessors, data collectors, and statisticians were also blinded to group allocations during the study.For the acupuncture group, after skin cleaning with 75% alcohol swab, sterile and disposable stainless steel needles  are quickly and perpendicularly inserted into the skin at P6 acupoints bilaterally to a depth of 20 mm. In this group, downward pressure and upward lifting combined with twirling the needle was used to achieve De-Qi sensation . The needles were kept in place for 30 min and manipulated manually every 10 min to maintain the De-Qi sensation. When the treatment period was over, all needles were carefully removed, and the puncture sites were covered with sterile swabs to avoid bleeding. Acupuncture was performed by licensed acupuncturists with more than 5 years of experience.For the sham acupuncture group, sham points, which are superficial, nonacupoints at the radial side of each wrist, 15 mm away from each P6 acupoint, were used . After sThe study period covered 72 h after surgery. A separate research nurse, not involved in the management of patients, recorded anesthesia time, surgery time, endotracheal intubation time, patient demographics, and preoperative data for each patient. Demographic and preoperative data included the following: age, gender, weight, acupuncture experience, and smoking history. Another blinded observer (nurse) recorded the postoperative data, which included assessing the postoperative pain score at rest. Pain scores were collected prospectively during the 72 h postoperative period using the Visual Analog Scale (VAS). Patients were asked to rate their pain on a 0–10 scale, where “0” represented “no pain” and “10” represented the “worst pain I have ever experienced.” The data were recorded by the nurse. The physicians recorded the use time and dosage of rescue analgesia (tramadol) for each patient when they requested rescue therapy, and the records were handed over to the observer for assessment. The incidence of postoperative nausea and vomiting was recorded. Assessments were performed at 24, 48, and 72 h. Reasons for withdrawal and acupuncture-associated adverse events (AEs), including bleeding, subcutaneous hemorrhage, hematoma, fainting, serious pain, and local infection, were recorded during the study.α = 0.05 (two sides) and β = 0.01 (power 90%). The resulting sample size is 31 patients per group. Estimating that 20% of patients might be lost means using at least 40 subjects per group. Intending also to observe the occurrence of postoperative nausea and vomiting, we set the sample size of each group at 60 cases in order to ensure statistical viability.Since there had been no previous studies on acupuncture to prevent postcraniotomy pain, we drew on the results of a similar study that used tramadol. In that study, there was an average VAS score of 3 in the tramadol group compared with 4.7 in the control group [t-test. Nonnormally distributed variables  were described as the median (interquartile range (IQR)) and were compared by the Mann–Whitney U test. A P value of <0.05 was considered statistically significant.All data input and the statistical analysis were performed in the Department of Epidemiology and Hygienic Statistics of West China Hospital of Sichuan University using SPSS 19.0. Data were checked for normality with the Kolmogorov–Smirnov test. Normally distributed variables were presented as the mean (SD) and were analyzed by a two-sample P > 0.05) , two in the acupuncture group and one in the sham acupuncture group, were withdrawn after they subsequently met the withdrawal criteria. Two of these suffered persistent coma, the other cognitive impairment. The data of the remaining 117 patients  were analyzed. The characteristics of the patients in the two groups—those receiving acupuncture or sham acupuncture—and their previous medical history were not significantly different ( > 0.05) .P=0.064). The VAS pain score of the acupuncture group, however, was lower than that of the sham acupuncture group, and this difference is statistically significant 24–48 h after surgery (P=0.002). There was no statistically significant difference in the VAS pain score of the two groups 48–72 h after craniotomy (P=0.254). There was no statistically significant difference between the two groups in the analgesic drug remediation at each period after craniotomy (P > 0.05) , though there was no statistically significant difference in the incidence of vomiting between the two groups during 48–72 h following craniotomy (P > 0.05). There was no statistical difference in the degree of nausea between the two groups 0–24 h, 24–48 h, and 48–72 h after surgery (P > 0.05)  reported AEs during the testing period. These patients had subcutaneous hemorrhage. All AEs were reported as mild, and none required special medical intervention. The two patients fully recovered from the AEs and did not withdraw from the trial.It has been accepted in the past that the pain accompanying intracranial surgery was minimal and, when present, dangerous to treat. As a consequence, analgesic therapy for this group of patients has generally been modest . It is nThe results of this study indicate that acupuncture at the P6 acupoint can reduce postoperative pain after craniotomy and may also reduce the incidence of vomiting in patients following craniotomy. This study found that patients had moderate-to-severe pain after the procedure, and the pain is more obvious during the first postoperative 24 hours. In both sham acupuncture and acupuncture groups, the VAS scores were gradually decreased in the 24–48 h period after surgery. This result is similar to a previous study indicating that postoperative pain began to decrease from 24–48 h .The acupuncture and sham acupuncture groups displayed no difference in postoperative pain scores 0–24 h after surgery. A possible explanation for this finding is that intraoperative fentanyl may help to alleviate VAS mainly in the early postoperative period. The VAS pain score in the two groups during 24–48 h after surgery, however, did show significant difference. This result is consistent with the conclusion of Mali's study which indicated that multiple electroacupuncture stimulation at different time points can reduce the VAS pain score of postoperative patients with gastrointestinal tumors within 72 h . This isμ-opioid receptor agonist that releases serotonin and inhibits the reuptake of norepinephrine. It is used for the management of postoperative pain in neurosurgical patients in our institution. Tramadol can provide effective pain relief without the side effects associated with opioids or the inhibitory effects on platelets induced by NSAIDs. Analgesics such as paracetamol and NSAIDs are less frequently used perioperatively to treat postoperative pain in our institution.Tramadol is a weak This study indicates that acupuncture at the P6 acupoint cannot reduce postoperative analgesic drug (tramadol) use during postoperative 0–72 h. The application rate of analgesic drugs is 8.6% which is much lower than what was found in previous domestic research . The frePONV is a common complaint after craniotomy, with an incidence of up to 79% . It can Our study indicates that acupuncture at the P6 acupoint can reduce postoperative pain, as well as reduce the incidence of vomiting in patients following craniotomy.Previous studies have shown that nausea and vomiting can also occur within the 24 h postoperative period , 25. ThiThe acupoints and modes used for stimulation may significantly affect the outcome of acupuncture for postoperative nausea and vomiting and postoperative pain relief. In our previous study, we found that P6 acupuncture can reduce the degree of postoperative nausea and postoperative pain . The P6 This is a single-blind, placebo-controlled, randomized trial. The De-Qi response is particularly important. The needle points that readily produce a strong De-Qi sensation are thought to provide better efficacy in patients. Acupuncture stimulation patients were awake during this study, so they were able to confirm the De-Qi sensation. We used shallow skin penetration at nonacupoint caves in the control group so that patients received a sting from the needle, but the possible efficacy of acupuncture was eliminated. The evaluators did not know to which group the patients belonged to. This renders the findings more reliable. However, the degree of pain and nausea evaluation indicators may be dependent on the patient's educational level, and understanding of the degree of pain may affect the results of the study.  Patients' preconceived expectations of acupuncture treatment may affect their perceptions regarding the effects of the treatment on their pain and nausea. We should, in further studies, conduct questionnaires asking patients about their expectations of acupuncture treatment.  Blinding between the two groups was not evaluated by asking participants to guess to which group they were assigned at the end of the intervention.  We found that there were potential patients unwilling to take part in the study due to their fear of pain caused by acupuncture treatment. Further studies could possibly use more painless treatments such as auricular bean-embedding therapy or intradermal needling.  There have been very few studies of this surgery type, mainly carried out within the same institution. This makes comparing the results with other independent researchers difficult. Our results will hopefully encourage other groups to carry out similar research.Our study has some limitations:Compared with the sham acupuncture group, the true acupuncture patients treated using the P6 acupoint experienced reduced levels of pain after craniotomy during the 24–48 h postoperative period. The incidence of vomiting within the 24 hours following craniotomy was also reduced. In addition, the acupuncture treatment also proved safe for patients.