Surprisingly, Cattoni et al.  reportedet al. .et al. [In this study, Spaans et al.  performeIn particular, they examined the clinical data of 5573 patients, calculating the mean pain score on a 0–10 scale at 24, 48 and 72 h after surgery; moreover, as a secondary outcome, they analysed postoperative nausea and vomiting, additional opioids, the use of rescue analgesia and length of hospital stay. The prediction of the pain level and its treatment is crucial because the incidence of chronic chest pain after video-assisted-thoracoscopic surgery must be considered [From a cursory reading of this article, one may conclude that, with the same pain score, unilateral loco-regional techniques have a shorter length of stay and a lower incidence of postoperative nausea and vomiting than thoracic epidural analgesia; despite the outcomes have been calculated by a random-effect meta-analysis, and hence can guide us to credible conclusions, the authors point out that these conclusions cannot be drawn because the pooled results show an excessively high level of variability and heterogeneity between studies.Adding the presence of confounding factors, such as study design , different thoracoscopic approaches (single-port versus multi-port) and the existence of local practices of analgesic protocols, a meta-analysis and comparisons between different analgesics are unreliable.Even though thoracic epidural analgesia in pain management in lung surgery has been used for decades, the recent PROSPECT guidelines support the loco-regional analgesic techniques discouraging the use of thoracic epidural analgesia due to its association with epidural haematomas and hypotension . It has In conclusion, the exciting issue examined in this study needs further investigation and more rigorous clinical evidence, with a well-designed randomized trial comparing loco-regional analgesia techniques to thoracic epidural analgesia to understand the best analgesic procedure that can benefit most patients undergoing thoracoscopic lung resections.


The world has been threatened with the emergence of the Novel Corona Virus straining the health care system and creating a global pandemic. This is not the first pandemic, and it certainly will not be the last to affect humanity. As the medical community is exposed to these highly contagious new diseases with arrays of symptoms like fever, cough, shortness of breath, anosmia, insomnia, and myalgia. Back pain can also be considered as one of the symptoms of COVID-19 infection. Therefore, this study aimed to find out the prevalence of back pain among the Health care workers who were tested positive for COVID-19 by the end of their isolation period.This descriptive cross-sectional study was done from April 2021 to June 2021 in KIST Medical College and Teaching Hospital, Imadol, Lalitpur, Nepal, after receiving ethical approval from the Institutional Review Committee (Registration number: 2077/078/57). Convenience sampling was done. Data collection and entry were done in Microsoft excel, point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data.Out of 156 COVID-19 positive patients, the prevalence of back pain was seen among 64 (41%) patients . Among them 21 (32.8%) were males and 43 (67.2%) were females. Likewise, the minimum age was 20 years and the maximum was 68 years with a mean of 33.5±10.28.This study demonstrated that a high proportion of healthcare workers were suffering from back pain and the findings are comparable to the data from other international studies. The study was carried out after receiving ethical approval from the Institutional Review Committee (Registration number: 2077/078/57). The study was done among HCWs including doctors, nurses and paramedics , hospital attendents and the administrative staff. All the HCWs who were tested positive for COVID-19 with Polymerase Chain Reaction (PCR) and gave consent were included in the study. Exclusion criteria of the study were those who had chronic back pain (more than three months) and who did not give written consent. Convenience sampling was done and the sample size was calculated using the formula,2 × p × q / e2n = Z2 × 0.5 × (1-0.5) / (0.08)2  = (1.96)  = 150Where,n = minimum required sample sizeZ = 1.96 at 95% Confidence Interval (CI)p = prevalence taken as 50% for maximum sample sizeq = 1-pe = margin of error, 8%The required sample size was 150, however, 156 responses were included in the study. This data was retrieved from the hospital database. All data were collected after informing participants about the study objectives and significance of the study.5Once the written consent was taken, data were collected using the structured questionnaire which included detailed information regarding sociodemographic characteristics, like sex, age, marital status. Different occupational attributes, like working hours per day, department and physical activities were also noted. Those who had back pain during and after being COVID-19 positive were further asked to locate the site of pain like neck, shoulder, thoracic area, or lower back. The participants also needed to grade the severity of pain using the Visual Analog Scale (VAS) scoring system, during, and after the isolation period. It was pre-defined that patients with VAS pain scores of 0 had no pain, 1 mm to 30 mm were categorized as having mild pain, those with scores of 31 mm to 69 mm were categorized as having moderate pain, likewise 70 mm to 99 mm as severe pain and 100 mm as extreme pain.All data were analyzed by Statistical Package for the Social Sciences (SPSS) version 16 using appropriate statistical tools. Numerical data were analyzed using frequency, mean and standard deviation. Point estimate at 95% confidence interval was calculated along with frequency and percentage for binary data.Among the 156 COVID-19 positive patients 64 (41%)  of them developed back pain, out of which 21 (32.8%) were male and 43 (67.2%) were female. Likewise, the minimum age was 20 years and the maximum was 68 years with a M ean±SD, 33.5±10. 28. Back pain among the COVID-19 positive patients was more prevalent among the doctors 24 (37.5%), followed by nurses and paramedics 21 (32.8%), housekeeping staff 11 (17.2%), and administration staff 8 (12.5%). Most of the infected staff with back pain were married 41 (64.1%).According to the VAS score, 7 (10.9%) patients had mild back pain, 33 (51.6%) had moderate back pain and 24 (37.5%) had severe back pain during the time of COVID-19 infection, which later on ( after 14 days) decreased to no pain in 16 (25%) patients, mild in 44 (68.7%), moderate in 3 (4.7%) and severe in only one (1.6%) patient.6 Around 80% of the patient with COVID-19 have mild symptoms and only the remaining 20% requires intervention.7Health care workers (HCWs) are exposed to infected patients for a long time and work overload with minimum rest during the time of COVID-19 place them at a high risk category. Only a few studies regarding COVID-19 with back pain have been conducted worldwide. However, there has not been such a study conducted in Nepal during the COVID-19 pandemic, so we have tried to find out the prevalence of back pain among the COVID-19 positive HCWs in a tertiary care hospital in Nepal. There is a wide array of symptoms for COVID-19 which are often nonspecific, but the identification of the symptom for early detection of the disease is crucial.8 In the same study male to the female percentage of back pain in COVID-19 positive patients were almost equal i.e. 46.6% and 53.3% respectively which was in contrast to our study which showed a female predominance of 67.2% as compared to male 32.8%. But, another study of COVID-19 patients conducted by Alkheraiji A, et al. showed a similar female predominance of 179 (63.7%) patients among 281 to have low back pain.9 A study conducted by Cuma Uz, et al. found half of their study population (50.5%) to have back pain during the time of COVID-19. They also constituted that patients with back pain had significantly higher pneumonia rates compared to those without.10 These studies were in concordant with the clinical data showing that 15% of patients with pneumonia had back pain.11 Another study carried out by Davis K found an association between COVID-19 pneumonia with severe back pain, he also observed cough and mild shortness of breath in patient with back pain.7In our study, the prevalence of back pain among the COVID-19 positive HCWs in a tertiary care hospital who stayed in isolation was 41%. This was similar to a study conducted by Murat S et al in Istanbul Medeniyet University which showed 36.8% of their admitted patient diagnosed with COVID-19 to have back pain.8 Similar study conducted in the kingdom of Saudi Arabia showed a high incidence of low back pain among COVID-19 positive patients which was 79% and was close to our study.9 Another study conducted by Sagat P showed an increase in the number of low back pain from 38.8% to 43.8% among the citizen of Saudi Arabia during the period of quarantine.12 We further divided our patients with back pain into thoracic pain 64.1%, neck pain 37.5%, and shoulder blade pain 23.4% as shown in In our study 81.2% patients had lower back pain, which was very high as compared to a study conducted by Murat S et al which showed only 44 (33.1%) patients to have low back pain among a total of 210 admitted COVID-19 patients.8 In our study, a VAS score of 6 was perceived in 23.4% patients which were maximum in number.According to the VAS score, 10.9% patients had mild back pain, 51.6% had moderate back pain, and 37.5% had severe back pain during the isolation period. This showed that the moderate type of pain was observed more in COVID-19 patients with back pain which was in contrast to the study conducted by Alkheraiji A et al which showed 25.3% of their study population to have moderate type of back pain during the time of COVID-19. In another study carried out by Murat S et al found moderate type of pain to be in maximum number.13 One more study carried out by Sahin et al. stated that the severity of back and neck pain during the time of COVID-19 infection increased as compared to the pre-infection period.14During the time of isolation lack of physical exercise could be one of the reasons in our study population to have back pain. A study conducted by Crisafulli et al. has shown physical activity to have therapeutic and protective effects on the cardiovascular, pulmonary, musculoskeletal, neuro logical, immune, and endocrine systems even during the time of COVID-19.8 As the symptoms of this disease can begin mildly, it can progress and lead to mortality, therefore it is necessary to have early diagnostic and treatment.At the time of our study, not all the PCR-positive patients were admitted to the hospital, only those patients who developed moderate to severe respiratory symptoms were admitted. Thus in our study, only 7.8% patients required hospitalization. Non of them were admitted due to severe back pain, rather all of them required intravenous medicine and oxygen support. Opposing to our study carried out in Istanbul showed pain to be one of the most common complaints for admitting the patient to hospital with COVID-19 which accounted nearly half of their admitted patients.This study was done in a single institute with a limited sample size among the HCWs. Thus the findings may not be generalised. Further studies must be done in a larger sample size.This study demonstrated that a high proportion of healthcare workers were suffering from back painand the findings are comparable to the data from other international studies. Coronavirus is a new disease to mankind with different presentations, we as HCWs will have to deal with this disease in the months to come. As back pain could be one of the presenting symptoms of a patient visiting the Out Patient Department (OPD), the examining and attending HCWs must take proper precaution with necessary social distancing to avoid nosocomial transmission of the virus. Therefore it may be imperative to implement back pain as one of the symptoms of COVID-19 for early diagnosis of the disease to mitigate further devastation.


The prospective randomized controlled trial.This study compares outcomes in terms of early postoperative anterior wrist pain and time to return to work or activities of daily living of patients who underwent carpal tunnel syndrome (CTS) release with short incision and those who had minimally invasive surgery (MIS) with CTS kits.A total of 24 patients diagnosed with primary CTS confirmed with electrodiagnosis at an academic university hospital were randomly assigned into one of two groups of 12 patients each: a short incision group and an MIS with tool-kit group using computer-generated block randomization (block of four). Sequentially numbered, opaque, sealed envelopes were used in the allocation concealment process. In the short incision group, skin was incised longitudinally from Kaplan’s line to the area distal to transverse wrist crease (2.5–4.0 cm) while in the tool-kit group, an incision of less than 2.5 cm. was made using special MIS-CTS kits. Primary outcomes evaluated include visual analogue scale (VAS) measurement of pain intensity in the anterior carpal area both while at rest and while conducting daily activities at the 2nd week postoperatively as well as the time to return to activities of daily living and work. Improvement in the Michigan hand questionnaire (MHQ) score, a secondary outcome, was also measured at the 2nd week postoperatively. Patients, allocator and outcome assessor were blinded.p > 0.99), while conducting daily activities (p = 0.89) and time to return to activities of daily living (p = 0.46) and work (p = 0.24). The MHQ score improvement at the 2nd week postoperatively showed no significant difference between the groups (p = 0.95). The MIS wound length in the tool-kit group was significantly shorter than in the short incision group .Demographic data, including preoperative electrodiagnostic severity and occupation, were similar in the two groups. There were no significant differences in terms of VAS of the early postoperative anterior carpal area at rest . Registered 30 May 2020.The online version contains supplementary material available at 10.1186/s12891-022-05663-5. Carpal tunnel syndrome (CTS) is the most common compressive neuropathy in the upper extremity, causing pain, numbness, tingling and weakness of the hand and leads to long-term work disability , 2. The There is evidence that surgical release provides better results than conservative treatment in terms of reduced symptom severity and improved function at 6 months after treatment –10. MetaThe standard incision is generally defined as a long, curvilinear palmar incision , 17. PreA recent meta-analysis reported that a limited incision allows an earlier return to normal activities than the standard incision . There wThe aim of this study is to compare early postoperative anterior wrist pain and time to return to work or activities of daily living between short incision and MIS with tool-kit in patients who underwent CTS release.A prospective, single center, randomized, parallel-group superiority trial was conducted at an academic university hospital between June 2020 and December 2021 following the CONSORT  statement . A totalDemographic data, including age, sex, dominant hand, affected hand, graded severity  , underlyPatients were randomly assigned to receive one of the two interventions, either short incision or MIS with tool-kit, using computer-generated block randomization (block of four). After randomization, sequentially numbered, opaque, sealed envelopes prepared by a person not involved in the trial were used in the allocation concealment process. The envelopes were opened just prior to skin preparation by the surgeon. All surgical procedures were performed by an experienced hand surgeon (PA) who was not involved in the outcome assessment process, and all patients were advised not to observe the operation. Thus, patients, allocator and outcome assessor were blinded to the study.The operations were performed in a minor operation room. All patients received 5–10 mL of 1% lidocaine with adrenaline 1:200,000 subcutaneous injection as wide-awake local anesthesia with no tourniquet (WALANT).A 2.5 to 4.0-cm-long incision was made along the line of the radial axis of the ring finger from Kaplan’s cardinal line to the area distal to the transverse wrist crease. After that, the subcutaneous tissue was bluntly dissected with a Stevens scissor and retractors were used to separate the borders of the incision. The palmar fascia was identified and divided. Then the transverse carpal ligament was identified and the mid portion of the ligament was incised with a no. 15 scalpel to provide access to the carpal tunnel. Stevens scissors were used to sever the distal and proximal portion of the transverse carpal ligament. Complete transverse carpal ligament release was confirmed by direct observation using a Ragnell retractor to maintain a clear surgical field  which was developed by Wongsiri et al. from Prince of Songkla University, Hat Yai, Tailand for MIS carpal tunnel release with Wongsiri technique . A 1.5–2Patients were allowed to move their wrists, hands and fingers the same day that the surgery was performed. No wrist splint was needed. Non-steroidal anti-inflammatory drugs or tramadol  were taken for a few days for postoperative pain control. Oral antibiotics were administered for a week. The original dressing and the surgical stitches were removed after 12 days.In cases where complete transverse carpal ligament release could not be confirmed due to limited direct visualization, the incision was extended proximally to the wrist crease (standard incision).The primary outcomes were postoperative anterior wrist pain at the 2nd week (postoperative days 12–14) and the time to return to work or activities of daily living. Postoperative anterior wrist pain was defined as pain from the surgical wound, scar or pillar pain  that cauSecondary outcomes were functional and symptom severity improvement which were evaluated using the Thai Michigan hand questionnaire at the day before surgery and at the 2nd week postoperatively (postoperative days 12–14) .The sample size was estimated using the formula for a randomized controlled trial for continuous data according to the study of Saw et al. . The aveEstimated sample sizes for a two-sample means test.t test assuming SD1 = SD2 = SD.Ho: m2 = m1 versus Ha: m2! = m1.Study parameters: alpha = 0.05, power = 0.80, delta = − 1.00, m = 2.5, m2 = 1.5, SD = 0.6.Estimated sample sizes: total number = 14, number per group = 7.A total of 7 patients in each group were needed to achieve 80% statistical power at the 5% significance level to detect the size of the input effect. To compensate for potential patient dropouts, we used a sample size of 12 patients per group. There is no generally accepted minimal clinically significant difference in time to return to work or activities of daily living. For that reason, we used the sample size mentioned above. We hypothesized that the time to return to work or to activities of daily living would be correlated with postoperative anterior wrist pain, i.e., the less postoperative anterior wrist pain, the earlier the return to work and/or activities of daily living.P-value of less than 0.05 was considered statistically significant.The trial compared the outcomes in patients who underwent MIS with tool-kit and those who had a short incision in terms of postoperative anterior wrist pain, time to return to work or activities of daily living, and functional and symptom severity improvement. Continuous variables, i.e., postoperative anterior wrist pain, time to return to activities of daily living and functional and symptom severity improvement, were evaluated using the Mann-Whitney rank-sum test as the data were nonnormally distributed. Continuous variables, including time to return to work and wound length, were assessed using the Student’s t-test as the data were normally distributed. Statistical analysis was performed using Stata Statistical software 15 . A n = 24) were assigned to one of two groups, either the short incision group or the MIS with tool-kit group in a 1:1 ratio. After randomization, the number of patients in both groups was equal (12 patients per group). One patient in the MIS with tool-kit group failed to appear at the scheduled follow up and was dropped from the analysis , sex (P = 0.22), dominant hand (P > 0.99), affected hand (P = 0.68), severity as determined by electrodiagnosis measurement (P > 0.99), underlying diabetes mellitus (P = 0.48) or occupation (P = 0.49) (Table There were no significant differences in demographic data between the MIS with tool-kit and the short incision groups in terms of age (9) Table .Table 1PP = 0.89) and time to return to activities of daily living (7 (SD 4) days vs 6 (SD 3) days, P=0.46) and work (14 (SD 8) days vs 11 (SD 5) days, P=0.24). MHQ score improvement, the secondary outcome, showed no significant difference between the groups (9 (2-31) vs 13 (1-32), P=0.95). The MIS with tool-kit group, however, did have a significantly shorter wound length than the short incision group (1.95 (SD 0.47) cm vs 2.92 (SD 0.56) cm, P < 0.01) (Table There was no significant difference between the MIS with tool-kit and the short incision groups in the primary outcomes: VAS of anterior wrist at rest (0(0–0) vs 0(0–0), P > 0.99) and while conducting daily activities (00–1) vs 0(0–1),  vs 0. We realized that comparable results occurred because of both MIS with double small incision and endoscopic groups had the small difference of surgical incision length  similar to our study. The different social security systems, with potential entitlement to paid sick leave in different countries might affect the time to return to work [The result in term of time to return to work in our study was similar to the randomized controlled trials which compared MIS with double small incision technique  to endoscopic technique (double 1.0-cm incisions) for CTS release . The tim to work .In this trial, no patients had their dressing changed prior to the 2nd week postoperatively and postoperative anterior wrist pain was evaluated prior to removal of the dressing to ensure that all patients remained blinded regarding the type of operation performed. No patients took the oral pain-control medication for more than 3 days after the operation, so the effect of oral pain-control medication did not affect the evaluation of postoperative anterior wrist pain at the 2nd week after surgical release. As both surgical techniques provided adequate visualization, no extended incision proximal to the wrist crease was performed with any of the patients.The short incision technique provided satisfactory outcomes in terms of anterior wrist pain and time to return to daily activities and work and were comparable to the MIS with tool-kit technique. The short incision technique did not require any special instruments which offered the benefit in term of cost-effectiveness unlike the MIS technique which required special tools to perform the complete transverse carpal ligament release under direct visualization. However, the MIS with tool-kit technique had the advantage of creating a smaller wound length and thus a smaller scar, making it preferable for patients concerned about cosmetic appearance and who could afford the extra cost.There are several limitations in this randomized controlled trial. First, the study only compared selected aspects between the MIS with tool-kit and the short incision approaches. Other aspects, e.g., satisfactory, grip or pinch strength, may have yielded different results. Second, the sample size was relatively small. Although the sample size of our study was adequate to interpret the primary outcomes, a prospective randomized controlled trial involving a larger population and a long-term follow-up is needed to confirm our results. Third, there is a limitation in terms of generalizability as this study included only Thais. Additional studies should be conducted in other populations. Fourth, after removal of the dressing, patients might have been able to discern the type of surgical technique they had received which could have biased the results for time to return to work and to activities of daily living. Fifth, since we used block of four in the method of randomization, the small block size could increase the risk that the allocation process might be predictable.There are no differences in terms of early postoperative anterior wrist pain or in time to return to work or activities of daily living between the short incision and the MIS with tool-kit techniques in patients undergoing CTS release. Short incision is recommended for benefit in term of cost-effectiveness, while the MIS with tool-kit method results in less surgical wound length which could be important for patients concerned with cosmetic appearance.Additional file 1. Results after carpal tunnel surgery in each group.


Although various treatments help reduce abdominal pain, real-world pain medication utilization among patients with Crohn’s disease (CD) or ulcerative colitis (UC) receiving advanced therapies is poorly understood. The aim is to understand the utilization of pain medication 12 months before and after the initiation of advanced therapies among patients with newly diagnosed CD or UC.®). The data from patients with use of pain medication over 12 months follow-up (after the initiation date of advanced therapies) were collected and analyzed. Differences in the use of pain medication 12 months before and after the initiation of advanced therapies were assessed using McNemar's and Wilcoxon signed-rank test.This retrospective, observational cohort study used administrative medical and pharmacy claims data of patients with CD or UC from HealthCore Integrated Research Database , opioids , and NSAIDs , while the use of neuromodulators significantly increased .Prior to initiating advanced therapies, 23.1% of patients with CD (N = 540) received nonsteroidal anti-inflammatory drugs (NSAIDs), 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators; similarly, 20.9% of patients with UC (N = 373) received NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators. After receiving advanced therapies for 12 months, patients reported a reduction in the use of steroids (78.1% vs. 58.9%, The use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators was common among patients with CD or UC. These results highlight that patients with CD or UC continued to receive pain medications even after initiating advanced therapies. Inflammatory bowel disease (IBD) is a chronic, progressive inflammatory disorder of the gastrointestinal tract, and includes Crohn’s disease (CD) and ulcerative colitis (UC) as its 2 major forms . The UniPain due to inflammation during the early phase of IBD, affects 50–70% of patients . ChronicTreating pain in patients with IBD can be challenging, as commonly used therapies such as nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and corticosteroids have been associated with an increased risk of disease exacerbation and other adverse outcomes , 15. HowThough various treatments show promising results in reducing abdominal pain , real-woThis retrospective, observational cohort study used administrative medical and pharmacy claims data of patients with CD or UC from the HealthCore Integrated Research Database (HIRD). The HIRD represents a broad, clinically, and geographically diverse spectrum of longitudinal claims data from US patients who are insured through Anthem’s commercial or Medicare Advantage health plans in the Northeastern, Southern, Midwestern, and Western regions. As of Q1 2019, the HIRD contained data of over 51 million individuals dating back to January 1, 2006. The HIRD is updated monthly with fully adjudicated paid claims.The data were used in full compliance with the relevant provisions of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). The study was conducted under the research provisions of Privacy Rule 45 Code of Federal Regulations (CFR) 164.514(E). This study was conducted in accordance with legal and regulatory requirements, scientific purpose, value and rigor, and follow Good Practices for Outcomes Research issued by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).Newly diagnosed adult patients with CD or UC from January 1, 2014 till July 31, 2017 using International Classification of Diseases (ICD), ninth revision, Clinical Modification (CM)  and tenth revision  codes were included. Other inclusion criteria were ≥ 2 claims for advanced therapies of interest following CD or UC diagnosis between the first diagnosis of CD or UC and the end of the study period, having ≥ 1 year of continuous health plan enrollment prior to the initiation date of advanced therapies (index date), and ≥ 1 year of continuous health plan enrollment after index date.In patients with CD, the following US Food and Drug Administration (FDA)-approved advanced therapies were included: natalizumab, certolizumab pegol, adalimumab, infliximab, vedolizumab, and ustekinumab. Similarly, in patients with UC, the following FDA-approved advanced therapies were included: adalimumab, infliximab, golimumab, vedolizumab, tofacitinib, and ustekinumab.Patients with juvenile idiopathic arthritis or those with other/multiple autoimmune conditions such as ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were excluded. Also, patients with both CD and UC were excluded from the study.Data on demographic and clinical characteristics, and the use of pain medication over 12 months follow-up (after the index date), were collected and analyzed.Any chronic, unclassified pain condition  was identified during baseline period and classified according to Romanelli et al. . The numPain medications included NSAIDs, glucocorticoid steroids, non-narcotic analgesics, opioids (chronic opioid use ≥ 180 days), and neuromodulators . The frequency or percentage of patients with ≥ 1 fills and number of fills of each pain medication listed were reported during the baseline period and first year after the index date.Adherence to advanced therapies was measured by the proportion of days covered (PDC) as defined in literature . The PDCContinuous variables  were presented as mean and standard deviation values. Categorical variables such as pain medication use before and after initiating advanced therapies were presented as relative frequencies and percentages. McNemar’s and Wilcoxon signed-rank tests were used to compare changes in pain medication use before and after the initiation of advanced therapies. Generalized estimating equation models were used to examine the total number of pain medication fills in CD and UC cohorts over time. These models controlled for patient demographics, clinical characteristics, and accounted for within-subject variations over time. As the outcome was over-dispersed, negative binomial regression with log link functions and unstructured correlation was selected based on model fit. Determination of model baseline covariates  were based on clinical importance and finalized after review of the univariate analysis.The analyses included 540 and 373 patients with CD and UC, respectively Figs. , 2.Fig. Baseline demographics and clinical characteristics of the patients included are presented in Table The mean ± SD age of patients with CD and UC were 36.8 ± 14.6 years and 39.9 ± 15.2 years, respectively. Most incident cases with CD (50.9%) and UC (43.2%) belonged to the age category of 18–34 years. A total of 50% of patients in the CD cohort were females and 44% were females in the UC cohort. Majority of the patients with CD (35.6%) or UC (32.7%) were from the Southern region of the US. The mean time from diagnosis to the initiation of advanced therapies was 7.1 months for the CD cohort and 10.9 months for the UC cohort.Before the initiation of advanced therapies, 23.1% of patients with CD were prescribed NSAIDs, 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators; similarly, 20.9% of patients with UC received NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators , opioids , and prescription-based NSAIDs , while the use of neuromodulators significantly increased  . On the other hand, non-adherent patients had 17% more pain medication fills/administrations , neuropathies/neuralgias , middle age group , and female patients .The number of pain medication fills were significantly associated with presence of baseline conditions such as back/cervical pain  and non-adherent patients  and presence of other baseline conditions such as hypertension  and mental illness/substance use disorders  were associated with higher number of pain medication fills.The age of patients  followed by corticosteroids were the most common initial treatment for UC . While tP < 0.05, t-test) and UC  [A recent study using the Truven MarketScan Commercial Claims and Encounters database has shown that an increasingly larger proportion of patients were treated with advanced therapies from 2007 to 2015  relative to more stable use of immunomodulators or 5-ASA  and simi t-test) . We obseThe current analysis corroborates the patterns observed in previous work where the first advanced therapy was initiated in CD and UC cohorts after the use of corticosteroids and immunomodulators . We obseOf the approved advanced therapies for CD or UC, TNFi and α4β7 integrin receptor antagonists were commonly used , 36. In To our knowledge, this is the first study reporting claims-based real-world data on pain medication use by patients with CD or UC on pain medication use before and after the initiation of advanced therapies. The current data highlight the prevalence of pain medication use in newly diagnosed patients with CD or UC.This study has some limitations. It was not possible at all instances to know the circumstances for which patients were using pain medications . Although we assessed pain medication use among patients with IBD, we cannot ascertain if the pain medication was prescribed for IBD specifically. Thus, it was not possible to stratify patients according to disease activity or severity. Although we assessed pain medication use among patients with IBD, over-the-counter pain medication use was not assessed. We cannot ascertain if the pain medication was prescribed for IBD specifically. The study population was limited to US patients who were insured , which could impact the applicability of the results to other populations . There may be errors in the diagnosis of disease as coded on claims recorded in the databases. We did not include over-the-counter use of pain medication and had the short follow-up period of 12 months after the initiation of advanced therapies which does not address long-term trends in disease course and pain treatment therapies.In summary, the findings reported here suggest that use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators is common among patients with CD or UC. Additionally, the results highlight that those patients with CD or UC continued to receive pain medications even after initiating advanced therapies. These findings are clinically relevant because they suggest the complexity of IBD pain management. These data expand the literature on pain medication utilization for IBD abdominal pain, especially the role of advanced therapies. Future research is needed to develop better treatment plans for abdominal pain in IBD.


Most adults presenting with chest pain will not receive a diagnosis and be recorded with unattributed chest pain. The objective was to assess if they have increased risk of cardiovascular disease compared with those with noncoronary chest pain and determine whether investigations and interventions are targeted at those at highest risk.We used records from general practices in England linked to hospitalization and mortality information. The study population included patients aged 18 years or over with a new record of chest pain with a noncoronary cause or unattributed between 2002 and 2018, and no cardiovascular disease recorded up to 6 months (diagnostic window) afterward. We compared risk of a future cardiovascular event by type of chest pain, adjusting for cardiovascular risk factors and alternative explanations for chest pain. We determined prevalence of cardiac diagnostic investigations and preventative medication during the diagnostic window in patients with estimated cardiovascular risk ≥10%. There were 375 240 patients with unattributed chest pain (245 329 noncoronary chest pain). There was an increased risk of cardiovascular events for patients with unattributed chest pain, highest in the first year , persistent up to 10 years. Patients with unattributed chest pain had consistently increased risk of myocardial infarction over time but no increased risk of stroke. Thirty percent of patients at higher risk were prescribed lipid‐lowering medication.Patients presenting to primary care with unattributed chest pain are at increased risk of cardiovascular events. Primary prevention to reduce cardiovascular events appears suboptimal in those at higher risk. This study of over half a million patients using linked primary and secondary care data has shown that patients presenting to primary care and recorded with unattributed chest pain are at increased risk of coronary events over the following 10 years.Primary prevention, such as prescribing of lipid‐lowering medication, to reduce future cardiovascular events in those at higher risk appears suboptimal.Better targeting to identify those most at risk for investigation and preventative measures may help reduce the population burden of cardiovascular events given the high incidence of patients with unattributed chest pain in primary care.Each year, between 1% and 3% of adults will present for the first time in primary care with chest pain.In our previous study of 172 000 patients presenting for the first time with chest pain in UK primary care between 2002 and 2009,The objectives of this study were first, to assess if there is an increased long‐term (10 year) risk of cardiovascular disease, coronary heart disease, myocardial infarction, and stroke in a national cohort of patients presenting to primary care with new unattributed chest pain compared with those recorded with a noncoronary cause of chest pain, and to assess how this risk varies over time. Second, we aimed to determine whether investigations and interventions in primary care are targeted at those most at risk and assess whether these have increased over time. We validated our findings in a second primary care electronic health records database.http://www.CPRD.com/. Code lists used to define chest pain and cardiovascular disease are given in Table www.keele.ac.uk/mrr. The study was approved by the CPRD Independent Scientific Advisory Committee (ISAC ref 19_205) and the ISAC protocol made available to reviewers. CPRD has ethics approval from the Health Research Authority to support research using anonymized patient data. General practices provide consent for CPRD to collect de‐identified primary care data from their practice. Individual patients can opt‐out of sharing their data for research and CPRD does not collect data for these patients. Additional informed consent is not required. The data were analyzed in accordance with the relevant guidelines.Data may be obtained from a third party and are not publicly available. The data were obtained from the Clinical Practice Research Datalink (CPRD). CPRD data governance does not allow us to distribute patient data to other parties. Researchers may apply for data access at The primary analysis used the CPRD Aurum database, a primary care electronic health records database containing anonymized, routinely recorded information from over 20 million patients in over 1000 general practices in the United Kingdom that use EMIS Web software.Validation of findings used the CPRD GOLD database,The study population was all patients aged 18 years or over with a first (incident) coded record of chest pain denoted as chest pain with cause unattributed, or chest pain attributed to a noncoronary cause, in primary care between 2002 and 2018. Those with a record of cardiovascular disease (as defined below) before their first recorded presentation of chest pain, or with <2 years of registration at their general practice at the time of their first chest pain event, were excluded. Index date was defined as the date of the first record of chest pain.Up to 2018, UK primary care used Read codes to electronically record morbidity and processes of care. Our definition of unattributed chest pain included symptom codes not clearly specifying a cause of the pain, such as chest pain not otherwise specified and chest tightness. Noncoronary chest pain included recorded codes with specific attribution to organ systems other than cardiovascular such as costochondritis. Read code lists were derived through consensus work in our previous study.The first 6 months after index date was defined as the diagnostic window to allow time for investigations and diagnosis related to initial presentation to occur. We excluded those with a diagnosed cardiovascular disease in the first 6 months (diagnostic window) after index date and those with follow‐up time of <6 months from index date. Patients with initially unattributed chest pain at index date who received a record of noncoronary chest pain within the first 6 months were reallocated to the noncoronary group.We also defined as a comparator group, patients with newly recorded angina, defined through a Read code or at least 2 prescriptions for nitrates. Those with <2 years prior registration or a recorded myocardial infarction in the first 6 months after index date were excluded.The primary outcome was a cardiovascular event defined as any of fatal or nonfatal acute myocardial infarction, angina, coronary heart disease not otherwise specified, heart failure, ventricular arrhythmia, cardiac arrest, ischemic stroke, hemorrhagic stroke, stroke type not specified, transient ischemic attack, peripheral arterial disease, abdominal aortic aneurysm, sudden cardiac death, and percutaneous coronary intervention and coronary artery bypass graft surgery.Secondary outcomes were (1) coronary events including fatal or nonfatal acute myocardial infarction, angina, coronary heart disease not otherwise specified, percutaneous coronary intervention, coronary artery bypass graft surgery; (2) fatal or nonfatal acute myocardial infarction; and (3) stroke defined as ischemic stroke, hemorrhagic stroke, stroke type not specified, transient ischemic attack. Outcomes were captured from the primary and secondary care records and the Office for National Statistics death registry using previously derived and validated algorithms.Patients were followed from end of the 6‐month diagnostic window until earliest of outcome, end of their records in CPRD, and end of study period .Covariates included demographic and risk factors for cardiovascular disease as included in the QRISK3 algorithm.We determined the prevalence of cardiac diagnostic investigations and interventions  during the 6‐month diagnostic window in those patients with unattributed chest pain and rated as elevated risk using the QRISK3 algorithm, developed and validated in UK national primary care electronic health records.Incidence of cardiovascular and coronary events, myocardial infarction, and stroke were derived by type of chest pain per 10 000 person‐years. Flexible parametric survival analyses were used to compare risk of a long‐term outcome by type of chest pain, presented as hazard ratio (HR) with 95% CI. The optimal number of knots with evenly spaced centile positions for the restricted cubic splines were selected graphically and based on goodness‐of‐fit statistics, namely the Akaike Information Criterion and Bayesian Information Criterion. Models were derived unadjusted, adjusted for demographic characteristics and year of index date, further adjusted for factors included in QRISK3, and in the final model for all covariates. Because total cholesterol to HDL ratio was only recorded in 47% of patients in the chest pain groups, this covariate was included only in a sensitivity analysis by adding it to the final model and categorized as ≤4, 4 to 6, >6, and missing. A further sensitivity analysis added prescription of a lipid‐lowering medication to the final model. Time‐dependent effects were plotted over calendar time, with HRs computed at 12, 36, 60, and 120 months of follow‐up. Finally, interactions with year of index date were included to assess if risk estimates changed over calendar time, comparing index years 2002, 2006, 2010, and 2014 with follow‐up restricted to 36 months.Robust standard errors to account for clustering in practices were used. Nonlinearity of relationships with outcome for age and body mass index were assessed using fractional polynomials, but did not improve model fit or alter findings, so only linear terms were retained. Death from noncardiovascular cause was included as a competing risk. However, because this did not change the estimated HRs, estimates from models without competing risks are presented.Analyses were repeated for the secondary outcomes. Because angina is included in the definition of cardiovascular and coronary events, the angina group was only compared with the unattributed and noncoronary chest pain groups in relation to the myocardial infarction and stroke outcomes.We also descriptively explored the extent that investigations and preventative medication had been used in the unattributed chest pain group, whether this has changed over time, and how this compares to use in the noncoronary chest pain group. The associations of the covariates with an investigation and with a new lipid‐lowering prescription (in those without such a prescription in the 24 months before index date) were assessed using binary logistic regression.All analyses were conducted in CPRD Aurum and replicated in CPRD GOLD.In CPRD Aurum, the population aged ≥18 years ranged from 3 603 905 in 2002 to 4 517 075 in 2018. There were 375 240 patients with newly recorded unattributed chest pain, 245 329 patients with noncoronary chest pain, and 24 554 patients with angina in CPRD Aurum between 2002 and 2018. Baseline characteristics are shown in Table In CPRD GOLD, there was a higher ratio of patients with unattributed chest pain (n=226 186) to noncoronary chest pain (n=89 145), but baseline characteristics for each chest pain group were similar to the corresponding group of patients in Aurum Table . The medFigure Patterns were similar when restricted to coronary outcomes Figure  and 4 wiTwenty‐nine percent of patients with unattributed chest pain and 23% with noncoronary chest pain had 10‐year risk scores of 10% or more. Thirty‐eight percent of the higher‐risk unattributed chest pain group had received an investigation in the 6 months after index consultation, and 60% were prescribed any of the 4 preventative and cardiovascular medications. Most 85%) of those receiving interventions were not newly prescribed this medication; they had a relevant recorded prescription medication in the 24 months before index date. Thirty percent were prescribed a lipid‐lowering drug during the 6 months after index consultation . Strong associations were also found with type 2 diabetes, family history of cardiovascular disease under age 60 years, age 55 to 74 years, and obesity  text that generally cannot be accessed for research. It is possible angina was an underlying reason for some of the unattributed group, and undiagnosed angina has been shown to be as associated with poorer prognosis, including myocardial infarction and mortality, as those with diagnosed angina.Patients presenting to primary care and recorded with unattributed chest pain are at increased risk of coronary events over at least the following 10 years. However, current primary prevention to reduce future cardiovascular events appears suboptimal, even in those at higher risk. Better targeting to identify those most at risk for investigation and preventative measures may help reduce the population burden of cardiovascular events given the high incidence of patients with unattributed chest pain in primary care.The study was funded by the British Heart Foundation (ref PG/19/46/34307). K.P.J. is supported by matched funding awarded to the National Institute for Health Research Applied Research Collaboration (West Midlands). H.H. is a National Institute for Health Research Senior Investigator. His work is supported by Health Data Research UK (grant number LOND1), the National Institute for Health Research University College London Hospitals Biomedical Research Center, and the BigData@Heart Consortium, funded by the Innovative Medicines Initiative‐2 Joint Undertaking under grant agreement number 116074. The views and opinions expressed are those of the authors and not necessarily the views of the funders, National Health Service, National Institute for Health Research, or Department of Health and Social Care.None.Tables S1–S5Figure S1Click here for additional data file.


Introduction: Orofacial pain is a common occurrence in daily dental practice; it is frequently attributed to temporomandibular dysfunction, one of its major causes, followed by pathology of the salivary glands, without avoiding interference at the level of the pain pathways caused by complications of periodontal pathology. The main objective of this study is to identify an important cause of pain in the oral–maxillofacial territory by quantifying the changes at the salivary glandular level using stereological methods. The secondary objective of the present research is to identify the implications of periodontal changes as a consequence of salivary quantitative and qualitative changes, quantified using periodontal indices, on the balance of the temporomandibular joint, dysfunction of it being an important cause of facial pain and having a profound impact on the complex oral rehabilitation algorithm of each clinical case, a condition evaluated with the analysis of the results of the Souleroy questionnaire. Material and methods: In a retrospective study, we evaluated the clinical results obtained after applying complex rehabilitation treatment to 35 subjects, 20 women and 15 men with salivary and TMJ dysfunctions, selected between 2020 and 2021 from the Clinic of Maxillofacial Surgery, Iasi. Results and discussion: The most common symptoms of temporomandibular disorders (TMDs) that were identified through the Souleroy questionnaire were pain and different types of damage to the masticatory muscles. The most significant changes in elders are reported in the case of serous cells, which reduced their percentage volume from 46.7% to 37.4%. Conclusion: As regards stereological analysis in conjunction with histological images, there were significant changes in diameters, perimeters, and longitudinal axes in the adult patients as opposed to the elderly patients, which were also influenced by the type of pathology at this level. The scores recorded on the diagnostic Souleroy scale indicated a large number of patients with low efficiency and maximum stress levels: 20.0% in level 1, 25.7% in level 2, and 25.7% in level 3. The diagnosis of pain in the oral and maxillofacial territory represents a real challenge for dental medical practice because the territory concerned is common and the forms of manifestation may have similar irradiation trajectories which can create difficulties in identifying different pathologies. Thus, pathologies of the temporomandibular joint and salivary glands are responsible for pain in the oral and maxillofacial area, with a high prevalence and a sometimes disabling impact on the quality of life of these patients. The dynamics of saliva quality and quantity, directly dependent on the status of the salivary glands, have a decisive influence on the intra-oral status through the effects of cleaning and self-cleaning often associated with different degrees of periodontal damage, the complications of which can influence the pathways of pain manifestation at the orofacial level .The holistic integrative approach to pain in the oral–maxillofacial territory represents a relevant starting point for the conduct of the present study. It is known that the influence of general pathology at the oral–maxillofacial level creates specific channels of investigation and identifies pathognomonic signs for a specific disease, thus the association between temporomandibular joint dysfunction and salivary gland pathology in patients diagnosed with rheumatoid arthritis has been demonstrated. It is important to identify the particular situations in which a differential diagnosis between the two clinical entities is required. Thus, particular attention should be paid to the junction of these pathologies and the specific therapeutic management of the manifest forms of pain in the oral–maxillofacial territory influencing the different types of oral rehabilitation. The interconnecting aspects at the oral–maxillofacial level in terms of the cascading effect of temporomandibular pathology are reflected in a significant decrease in saliva associated with salivary changes. All these aspects plead for an integrative diagnosis to identify the specificity of pain in temporomandibular joint pathology compared to that triggered at the level of the salivary glands with the influence of periodontal status elements that individualize an entire vision of the diagnosis ,3.Temporomandibular disorders (TMDs), a group of chronic conditions, are considered the second most common musculoskeletal condition (after chronic low back pain) resulting in pain and disability. Pain-related TMD can affect an individual’s daily activities, psychosocial functioning, and quality of life. Patients with these symptoms often seek consultation with dentists for their TMD, especially for TMD-related pain .Diagnostic criteria for TMD with simple, clear, reliable, and valid operational definitions for history, examination, and imaging procedures are needed to render physical diagnoses in both clinical and research settings.TMD is an increasingly common diagnosis in the population with overt symptoms affecting the quality of life, and the prevalence of this condition in the adult population varies according to geographical location and the age range affected. In Saudi Arabia, the prevalence of TMD among students aged between 20 and 25 years was found to be 37%, while in Lebanon, the estimates were between 19% and 59.5% following questionnaire-based assessments, and in Poland, the prevalence of the condition was found to be 55% in urban areas ,5,6. In Salivary changes at the qualitative and quantitative level influence the oral status at the level of dental periodontal indices, the negative effects being found in patients with a low salivary volume that attracts cascading effects located at the dental periodontal level ,11,12. TThe anamnesis questionnaires have begun to be widely used as very important tools in diagnosis. These represent a method of investigation based on information provided by patients. These questionnaires are designed to provide important facts about the history of pain or a condition. The relevant starting points for choosing this type of questionnaire are represented by the existence of several types of pain at the level of the stomatognathic system, the maxillofacial space, characteristics such as irradiation of the essential elements in the sphere of differential diagnoses of the submaxillary glands and persistent pain at TMJ, and damage of the periodontal support tissue ,17,18.The information provided will help the achievement of a correct and individualized diagnosis. In the literature, the best-known pain questionnaires are the MPQ (McGill Pain Questionnaire)  and AVS The originality of the study consists in bringing the stereological method as a predictor of pain pathology triggered by salivary gland damage and in integrating the evaluation of the salivary glands in the differential diagnosis of pain, which manifests itself with a similar character in the oral–maxillofacial territory. Interdisciplinary assessment of pain in the oral–maxillofacial territory is extremely important and forms the basis for appropriate therapeutic planning so that the results are maintained in the long term.The working hypothesis on which this research is based is that pain in the oral–maxillofacial territory is a symptom encountered in different pathologies, the most common being associated with temporomandibular joint pathology and salivary gland pathology, the evaluation aspects of diagnostic elaboration and treatment-plan staging being carried out in the context of a cumulative factor.The main objective of this study is to identify an important cause of pain in the oral–maxillofacial territory by quantifying the changes at the salivary glandular level using stereological methods.The secondary objective of the present research is to identify the implications of periodontal changes as a consequence of salivary quantitative and qualitative changes, quantified using periodontal indices, on the balance of the temporomandibular joint, the dysfunction of it being an important cause of facial pain and having a profound impact on the complex oral rehabilitation algorithm of each clinical case, a condition evaluated with the analysis of the results of the Souleroy questionnaire.The study group included 129 patients hospitalized at the Maxillofacial Surgery and Oncology Clinic between 2020 and 2021 and diagnosed with salivary dysfunction and TMJ disorders. From this batch, 118 eligible patients were selected, of which those who also completed the full oral-rehabilitation stages and not only the pain-diagnosis stages were 35 patients who also responded positively to the follow-up stages.All patients had to fill in the associated questionnaire and, with consent, they were able to obtain a specific evaluation before the treatment based on the computerized program. (The present study was approved by the Ethics Committee of “Gr. Th. Popa” University of Medicine and Pharmacy Iasi TD 312/2008 and No. 176/17.04.2022. All protocols were in accordance with the provisions of the Declaration of Helsinki.) Our study focused on submaxillary salivary glands and had two main areas of approach.The patients included in our study are those who had not undergone chronic treatments at different stages of life, a very important and limiting criterion. The inclusion criteria for the cases were: patients suffering from salivary lithiasis, and pain in the oral maxillary territory.The exclusion criteria for the cases were: non-lithiasis patients and another pain type external to that of the stomatognathic system or oral–maxillofacial territory. We evaluated the clinical results obtained after applying complex rehabilitation treatment to 35 subjects, 20 women and 15 men, selected between 2020 and 2021 from St. Spiridon Hospital, Clinic of Maxillofacial Surgery and Oncology Hospital, Iasi, with salivary and TMJ dysfunctions. It is a retrospective study with limits according to the flowchart for patient selection .The first part revealed histological aspects. We studied submaxillary salivary glands using 35 samples harvested from the bodies of both genders, 20 women and 15 men, and various ages without pathological damage. The cases were divided into two groups of age: adults (25–59 years) and elders (60–72 years). The pieces were processed using the paraffin-embedding technique and colored with the usual (H&E) and special methods , which revealed differentiated structural components. A qualitative examination was performed of sections to remove any pathological aspects and to select the representative sections without processing artifacts.The second, microanatomic quantitative study was conducted using an interactive digital video software product applied to histological sections selected using standard measurement to assess the dimensions of secretory components.Standard measurements facilitated the assessment of dimensions like diameter, perimeter, area, long and short axis, and the roundness of the secretory units separately for the serous, mucous, and small needles.Quantifications were conducted on representative sections varying between 10×-80× objective, measuring, in each case, 20 secretory units of each type.For the stereological examination, the report automatically submitted the stereological volume aspect percentage, verifying the significance of the obtained data. Quantification was carried out only in the glandular lobules, without going into the interlobular spaces. A Weibel parallel grid stereological scale was used in our study; a test surface corresponding to 540 points on the test grid with Weibel parallels was registered with the 90× objective, with a distance between two points of 19.39 μm .Concerning the clinical assessment, particularly important issues are related to the identification of the Ramfjord index PDI  , gingival bleeding index (GBI), Silness and Loe plaque index (PLI), clinical attachment loss index (CAL), and the Community Periodontal Index of Treatment Needs (CPITN), which offers an in-depth view of present periodontal damage .To investigate the arsenal of diagnostic tools, we used the Souleroy questionnaire for revealing the most common symptom and quantifying the optimization obtained after treatment.This is a diagnostic scale used to evaluate the treatment efficiency by placing the patient in a stage of the pathological situation or the degree of optimization within a performed treatment .p < 0.05 was considered statistically significant and the value of p < 0.01 was considered highly statistically significant. The consent of all participants was obtained to meet the protocol of the scientific university ethical committee.The statistical analysis was performed in SPSS 27.0. The Kolmogorov–Smirnov test was used to check the distribution of the numerical variables. The numerical variables were expressed through average values and standard deviations, and the category values were expressed through absolute frequencies and percentages. The Pearson Chi-squared test was used to compare categorical variables within samples, and the t-Student test was used to compare numerical variables with normal distributions within the samples; Mann–Whitney and Wilcoxon Signed Ranks tests were used to compare numerical variables with non-normal distributions within the samples. The value of The results of the study provide the data in their analytical sequence, starting with the changes identified by correlating the stereological analysis with the histological analysis of the salivary glands evaluated, followed by the data related to the periodontal indices analyzed according to salivary qualitative and quantitative changes as a natural consequence of salivary gland pathology. In the next step, the results relate to the analysis of the Souleroy questionnaires with profound implications for the identification of the pain factor at the temporomandibular joint level. All these elements are reflected in the way in which complex oral rehabilitation is influenced by the intra-oral status, the type of existing prosthesis, and the quality of the dental–periodontal support, as well as the way in which periodontal parameters are improved with specific antibiotic therapy, in the context of the integrative context of diagnosis and therapy.The importance of microanatomical studies from a qualitative point of view is reflected in the detailed aspects of the structure of the salivary glands, a structure with deep implications for the diagnostic and therapeutic areas .Structurally, the major salivary glands are made up of numerous lobes made up in turn of lobules and connected by dense connective tissue in which excretory channels and neurovascular elements are found. The structural differences between the three pairs of major salivary glands are documented in the literature, the parotid gland being a serous type, mixed submaxillary gland and having sublingual mucosa cell representation.The presence of cellular condensations in the histological evaluations of the material studied, as well as acinar dimensional changes, serve as starting points and indications of inner functional deficiencies determined by functional changes.The values of the standard measurements obtained were introduced in centralizing tables according to the parameter, while the results were checked statistically.The most significant values were the area of the needles, the perimeter, the diameter, and the long and short axes according to which the roundness of the studied needles was assessed.For submaxillary glands, a predominantly serous structure has been observed containing mucous cells as well.In particular, serous acinus, rarely mixed acinus, serous cells forming the crescents, and rarely pure mucous acinus could be noticed. Striated ducts were noticed as being abundant.Special stains reveal the existence of connective septa, which divide the parenchyma but are less obvious than in the parotid gland literature.The old connective septa are thicker and branched. In addition, they are separated from fat which sometimes penetrates the lobules.Stereology affords the appreciation of the percentage volumes of intralobular structures. The reference structures were established: serous and mucosal cells, interlobular excretory duct cells, blood vessels, and connective tissue. The statistical and stereological aspects of the components of the salivary gland structure are presented in The most significant changes in elders are reported in the case of serous cells, which reduce their percentage volume from 46.7% to 37.4%; connective tissue, which becomes more abundant (increases from 12.2% to 17.9%); and the appearance of adipose tissue (7.2%), the latter replacing the functionally specialized elements.The diameters, perimeters, and longitudinal axes vary between the adult (25–59 years) and elderly patients (60–72 years) as follows :We identified a highly significant decrease in elders in the diameter, perimeter, and long axes of serous acini; the diameters of mucous and mixed acini are also diminished in elders, but not quite significantly, as well as the perimeter of mixed acini, while the long axes of mixed acini are also diminished, but statistically significantly; the perimeters and long axes of mucous acini are slightly increased in the elders compared with the adults. These variations related to age are justified by pathological and morphological changes.For the evaluation of the damaged dental–periodontal status condition, we used systematization through mean values indices.Regarding the intraoral clinical examination of the patient, the first important sign observed was periodontal damage, with a horizontal bone line at 33.10% and a vertical bone line at 27.93%.We identified statistically significant differences between adults and elders for all periodontal indexes investigated, except the PLI index—generally, all these indexes increased in elder patients; the most obvious discrepancies were observed in the case of the PDI and GBI indexes .In summary, the elder patients in our study group displayed moderate to abundant levels of plaque compared to mild to moderate plaque in the adult patients; all elder subjects were diagnosed with moderate to severe plaque-induced gingivitis compared to mild to moderate plaque-induced gingivitis in the adult patients; most of the elder patients were diagnosed with moderate to severe chronic periodontitis compared to mild to moderate chronic periodontitis in the adult patients.Inflammation is thus correlated to a decrease in the rate of salivary flow, with changes in the salivary glands that induce pathological aspects at the local, occlusal, and TMJ levels.The results based on the statistical analysis of the data resulting from the questionnaires on pain symptomatology were corroborated with the qualitative and quantitative evaluations represented by the stereological and histological investigations and the quantification of the dental periodontal and loco-regional indices at the TMJ level.Before proceeding to oral rehabilitation, we applied the Souleroy questionnaire as an initiator of the therapeutic plan, solving the first stage of mental rebalancing and craniomandibular cranial repositioning with the necessary therapeutic arsenal and then the morpho-functional aspect itself .p = 0.133).The main and common symptoms of TMDs very frequently consist of pain and accentuated stress. Related to this, the scores recorded on the diagnostic Souleroy scale indicate a large number of patients with low efficiency and maximum stress levels: 20.0% in level 1, 25.7% in level 2, and 25.7% in level 3. In the case of the adult patients, the situation is slightly better than in the case of the elders: only 1 adult patient has the minimum score of 1 (5.9%) compared with 6 elders (33.3%), 3 adults have a score of 2 (17.6%) compared with 6 elders (33.3%), and only 2 elders have an initial efficiency score of > 3 (11.2%) compared with 8 adults (47.0%). These differences are not statistically significant  is definitely more reliable and comfortable for elderly patients with TMD-associated dysfunction and submaxillary gland pathology (38.9%). Partial mobile rehabilitation was suitable in 40.0% of the patients, again more often in elder patients (55.6%) than in the case of the adults (23.5%), and the total mobile treatment was recommended for 2 patients (5.7%), both elders (11.1%), being also combined with a special treatment for prosthetic field lubrication because of the dysfunctionality of the salivary products. The prosthetic treatment was also combined, when necessary, with endodontic treatment (in 60.0% of cases) or surgical interventions (in 48.6% of cases); all patients received balneo-physio-kinesiotherapy. The mixed rehabilitation was also accompanied, when necessary, by mouth guards, oral medication, and prosthetic treatment for temporomandibular disorders with an average level of tolerability and success.Streptococcus aureus, especially among elderly people living in asylums. The infection is due to a virus, such as herpes; the treatment is usually symptomatic but may include antiviral drugs (prescribed in our context in 20.0% of cases)The specific treatment procedure for inflammation of the salivary glands and pain is represented by antibiotic therapy —dicloxacRegarding surgical interventions (28.6% of cases), abscesses required drainage; sometimes, a superficial parotidectomy or excision of the submandibular gland was indicated in patients with chronic or recurrent sialadenitis. In addition, because sialadenitis usually occurs after decreased saliva flow (hyposecretion), patients were usually advised to drink plenty of fluids and eat or drink things that trigger saliva flow. Warm compresses and gland massage can also be helpful if the flow is obstructed in some way.The results regarding the diagnostic Souleroy scale, obtained after applying the rehabilitation procedures and the antibiotic therapy, are depicted in p = 0.262), proving that the patients had a generally good response to the prescribed treatment.We noticed a certain decrease in stress levels—the scores on the Souleroy scale vary between 5 and 10 after treatment compared with 1–7 before treatment. Most patients have very good scores (8—28.6% of cases or 9–10—48.6% of cases). This improvement was noticed for both age groups investigated, even if the results are better in the adult patients  compared with the elder patients . The differences between age groups are not statistically significant either in this case  in order to evaluate the efficiency of specific interventions. The obtained results are described in The Souleroy scale scores significantly decreased after treatment in all cases, globally and separated by age group, some specific elements being also present. The best score improvements were observed in adult patients with fixed or partial prostheses, while the weakest improvement was observed in elder patients with mobile prostheses, with poor results also being noticed in the case of elder patients with partial prostheses. The endodontic treatment led to moderate improvements in the Souleroy scale score, as well as the surgery interventions—in this case, the improvements were even smaller, particularly for the adult patients. Among antibiotics, the best improvements in Souleroy scale scores were noticed in the adult patients who received dicloxacillin or vancomycin and the weakest in the adult patients who received antivirals. The elders’ response to antibiotics was weaker compared with the adults’ response; cephalosporine had a moderate effect on Souleroy scale scores in both age groups, as well as clindamycin; the antivirals registered a slight effect.In light of histological examinations performed on the salivary glands of healthy subjects, according to old literature from 1978 to 2000, Dayan revealed a significant reduction in the acinar volume and an increase in the volumes of stromal components, the highest volume being occupied by the inflammatory infiltrate ,22.The analysis of the normal structure of the salivary glands enables a morphogenetic interpretation of the histological types of pathological variabilities in salivary glands.It was observed that the stereological quantification performed shows differences in the secretory structural composition of the glands: in the submandibular, the percentage volume of serous cells predominates (42.0%).All types of glandular acini  atrophy in the elderly, the most affected being serous acini. Their damage could explain the increase in the viscosity of saliva in the elderly and the reduction of its ability to moisturize and wash the oral cavity.Standardized measurement of the acinar structures according to age and concomitant pathology helps us determine the structural changes that can influence a permissive and objective treatment in choosing the optimal rehabilitation therapeutic solution to facilitate the necessary functionality.The percentage of connective tissue increases in the elderly compared to adults; the septa thicken and penetrate deep inside the lobe along with the excretory ducts, compressing the secretory units. In the elderly, the secretory structures are reduced in size, as is their percentage volume, being replaced by adipose tissue that dissociates not only the secretory elements but also the connective tissue. The system of excretory ducts becomes irregular in both salivary glands studied and increases its volume by the lumens ,24. As aToday, the evolution of methods for assessing salivary gland status has made remarkable progress, with digital subtraction sialography becoming an increasingly common paraclinical method for assessing salivary gland morphology and identifying specific pathology. The choice of salivary gland assessment methods is fully in line with the availability of specialist services and especially with the socioeconomic status of the patients assessed.Periodontal diagnosis and control are based on clinical parameters to a large extent. The direct clinical diagnosis affects decisions to initiate treatment and the selection of methods and outlines the topographic area of application. Dentists also evaluate the outcome of treatment and attempt a long-term prognosis based on clinical parameters. Periodontal pocket formation and loss of attachment are pathognomonic signs of periodontal disease. Reduction in periodontal pocket depth and attachment gain are the goals of periodontal therapy. Periodontal pocket probing emerges as the obvious method for diagnosing disease and evaluating therapy. The main parameters assessed using periodontal probing are periodontal pocket depth , gingival recession , and clinical attachment level . The data obtained with digital methods provide useful information about the status of the salivary glands and their implications for the stomatognathic system.The treatment of temporomandibular disorders should address the problems identified in the subjective complaints of patients, especially the acute ones and those in the inflammatory stage, with the aim of relieving pain first, as well as muscle spasms ,28. In tAdditionally, in order to make functionality more efficient and solve other associative and stressful causes, we can also establish an occlusion plan: the prevention or correction of the mandibular dysfunctions through prosthetic rehabilitation ,37.The approach in the literature to the assessment of salivary gland morphology as correlated with saliva type is reflected in the studies conducted by Chen et al., who used the combination of ultrasonography with virtual touch quantification for the diagnosis of Sjögren syndrome. The results of the study indicate that the assessment of salivary gland damage, predominantly in the submandibular and parotid glands, contributes significantly to the diagnosis of Sjögren syndrome. Therefore, the development of non-invasive and accurate diagnostic strategies for salivary gland morphology and pathology would contribute significantly to the early diagnosis of Sjögren syndrome associated with markedly decreased saliva quantity. In future studies, we aim to assess the parameters involved in triggering the pain factor at the temporomandibular joint of the salivary glands and the periodontal level using digital techniques fully quantifying the initial status of the therapeutic need and the therapeutic possibilities in the context of the initial variables. Furthermore, we intend to include in the statistical analysis predictability studies that provide the limits within which the initial parameters characterizing the temporomandibular joint, salivary glands, and periodontal pathology evolve, with an assessment of the degree of oral rehabilitation according to specific therapeutic methods and evaluation of long-term outcomes ,39.As humans get older, the submaxillary glands undergo similar quantitative changes, the decrease in salivary flow and the change in saliva composition being challenged by qualitative and quantitative structural changes. Because most of the successful therapies are dependent on parenchymal gland impairment, it is essential to know the structure to create a track to new therapeutic approaches. Computerized quantitative methods play a particularly important role in quantifying age-dependent changes in the parenchymal and stromal structure of the submandibular glands in selected subjects without systemic disease by digital diagnosis, with profound implications for our diagnostic management plan .This outline circumscribes normal from pathological aspects and creates optimal premises and more precise approaches for the patients involved in the study, as well as in the case of overlapping associative pathologies of temporomandibular disorders, and generates a diagnostic panorama that can justify complex oral rehabilitation as well as its integrated and integral impact.It is important to have an adequate comprehension of the diverse causes of salivary gland pathology to develop a systematic approach that includes collaboration with physicians to facilitate interdisciplinary patient care, which involves systemic conditions and medication.Daily practice shows that the elements of therapeutic failure of oral rehabilitation are associated with the absence of an integrative assessment of the pain phenomenon caused by both temporomandibular joint pathology and salivary gland pathology, requiring a precise assessment and long-term monitoring. In order to prevent relapses, the evolving aspects of advanced techniques and technologies for the detection of oral–maxillofacial pathology have a definite impact on the accuracy of integrative pain diagnosis at this level. One aspect that should not be overlooked is that which is related to social cases and the low socioeconomic level of the patients. In these categories, the methods anchored in the register of stereology in conjunction with various classical imaging techniques at the level of the temporomandibular joint can lead to remarkable results in terms of prophylaxis, interceptive diagnosis, and complex long-term oral rehabilitation.The limitations of the study concern some aspects related to the fact that the patients in the initial study group, once they had resolved the pain phenomenon, did not continue with the rehabilitation stages, thus creating gaps in the consistency of the results and the completion of the questionnaires related to pain perception.We noticed in our study the existence of pathology in the salivary glands, expressed by the presence of pain easily overlapping with dysfunctional syndrome pain, as well as symptoms such as decreased salivary flow.As regards stereological analysis in conjunction with histological images, there were significant changes in the diameters, perimeters, and longitudinal axes in the adult patients as opposed to the elderly patients, which were also influenced by the type of pathology at this level. The most significant changes in elders were reported in the case of serous cells, which reduced their percentage volume from 46.7% to 37.4%.The scores recorded on the diagnostic Souleroy scale indicated a large number of patients with low efficiency and maximum stress levels: 20.0% in level 1, 25.7% in level 2, and 25.7% in level 3.In our study, the Souleroy scale scores significantly decreased after treatment in all cases, globally and separated by age group, some specific elements being also present. The best score improvements were observed in the adult patients with fixed or partial prostheses, while the weakest improvement was noted in the elder patients with mobile prostheses, with poor results being also noticed in the case of the elder patients with partial prostheses.The polyvalent approach to the pathology of the salivary glands is essential in correlation with changes at the salivary level. The methods of quantifying the acinar changes anchored in digital methods offer additional precision and manifest as an alarm signal in the integration of these changes in the case of stomatognathic system homeostasis.


It is unclear whether fascial plane blocks, such as serratus anterior plane (SAP) block, should be routinely performed for less extensive breast surgeries. Therefore, our goal in this retrospective cohort study was to evaluate the association of integrating SAP blocks into a standard perioperative multimodal analgesia plan in patients undergoing simple lumpectomies (without node biopsies) with perioperative opioid consumption. As secondary outcomes, we also analyzed postoperative pain scores and post-anesthesia care unit (PACU) length of stay.The potential benefit of regional interventions for simple lumpectomy breast cancer surgeries has not been well investigated. Understanding which patients to P-value of < 0.05 was considered statistically significant.This was a single institution retrospective cohort study  assessing the association of SAP blocks to our outcomes of interest. In the adjusted analysis, we created matched cohorts using 1:1  propensity-score matching using nearest neighbor-matching without replacement. To compare the primary and secondary outcomes in the matched cohorts, we used the Wilcoxon signed rank test. A P = 0.16). No differences were seen in the other outcomes.There were 419 patients included in the analysis, in which 116 (27.7%) received a SAP block preoperatively in addition to our standard perioperative analgesia plan. In an unadjusted analysis, no differences were seen in perioperative opioid consumption, PACU pain scores, and PACU length of stay. Among the matched cohorts, the median [quartile] perioperative opioid consumption in the surgical site infiltration only versus SAP block cohorts were 10 mg  and 10 mg , respectively (In this study, we evaluated the impact of SAP blocks on patients undergoing simple lumpectomies, which are relatively less involved breast surgeries. We concluded that routine use of preoperative regional anesthesia is not beneficial for these specific patients. Future studies should focus on identifying patients that would directly benefit from regional interventions. While tIt is unclear whether fascial plane blocks, such as SAP block, should be routinely performed for less extensive breast surgeries. Therefore, our goal in this retrospective cohort study was to evaluate the association of integrating SAP blocks into a standard perioperative multimodal analgesia plan in patients undergoing simple lumpectomies (without node biopsies) with perioperative opioid consumption. Thus, we compared two cohorts: SAP blocks  versus surgical site infiltration only. As secondary outcomes, we also analyzed postoperative pain scores and post-anesthesia care unit (PACU) length of stay. Patients in both cohorts received local anesthesia infiltration at the surgical site by the surgeon in addition to standard non-opioid and opioid medication administration.This retrospective study was approved by our institution’s (UC San Diego) Human Research Protections Program for the collection of data from our electronic medical record system and the informed consent requirement was waived. Data were manually collected retrospectively from the electronic medical record system by one clinician (S.M.) from the University of California, San Diego Healthcare System. The manuscript adheres to the applicable EQUATOR guidelines for observational studies.Data from all patients that underwent simple lumpectomy from a three-year period during 2019–2021 at our outpatient surgery center were extracted. Cases that included a concomitant surgery were excluded. For the subset of breast surgical patients undergoing a simple lumpectomy, the procedure is typically a small excision of a wedge of subcutaneous breast tissue. Depending on whether the surgery is performed medial or lateral to the nipple, the anterior or lateral cutaneous branches of the intercostal nerves will contribute innervation to the operative area, respectively. All patients were given preoperative acetaminophen (unless contraindicated). Intraoperatively, patients underwent either monitored anesthesia care with natural airway or general anesthesia with supraglottic airway. Anesthesia was maintained via propofol infusion and/or volatile anesthetic. Intravenous fentanyl and hydromorphone were given at the discretion of the anesthesiologist. Upon surgical closure, for all patients, the surgeon infiltrated local anesthesia (bupivacaine 0.25%) into the surgical field. Postoperatively, patients received fentanyl, intravenous hydromorphone, or oxycodone as needed.In 2021, our regional anesthesia team implemented the addition of preoperative SAP blocks. In the preoperative room, patients were placed in the lateral position (operative side up). Ultrasound-guidance placed in a coronal plane at the midaxillary line and rib 4, rib 5, latissimus dorsi, and serratus anterior muscle were identified. A 20-gage Tuohy needle was then inserted in-plane and directed towards rib 5. The needle was inserted caudad to the probe. Local anesthetic (ropivacaine or bupivacaine) with 1:400,000 of epinephrine was deposited deep or superficial to the serratus anterior muscle (ranging from 20 to 30 mL per side). Patients receiving the SAP block also received surgical site infiltration. Thus, patients from 2019 to 2020 were in the “surgical infiltration only cohort” and patients from 2021 were in the “SAP cohort”. No other significant changes occurred between the two cohorts with respect to surgical or anesthetic management.The primary outcome measurement was perioperative opioid consumption, which was defined as total opioid use intraoperatively and in the PACU – measured in intravenous morphine equivalents (MEQ). Secondary outcomes included median PACU pain scores , maximum PACU pain score (NRS), and PACU length of stay (minutes). Potential confounder variables that were collected included age, body mass index, American Society of Anesthesiologists score, history of anxiety, history of depression, history of chronic pain, breast mass size (measured in cm for largest dimension), whether surgery was bilateral, whether mass was located medial to the breast, and primary anesthesia type .All statistical analysis was performed using R (Version 3.6.1). We compared baseline characteristics and outcomes in the surgical site infiltration only and the SAP block cohorts. For continuous and categorical variables, we used Wilcoxon rank sum test and chi-square test, respectively, to assess statistically significant differences. In the unadjusted analysis, outcomes were compared using Wilcoxon rank sum test.P-values for each variable included in the model. A P < 0.05 was considered statistically significant.Next, we performed a multivariable linear regression modeling the use of SAP block with perioperative opioid consumption. In this model, we controlled for age, body mass index, American Society of Anesthesiologists score, depression, anxiety, chronic pain history, breast mass size, and bilateral surgery. We reported the estimates, standard errors, and P-value of < 0.05 was considered statistically significant.To create matched cohorts, we performed 1:1  propensity-score matching using nearest neighbor-matching without replacement. For this, we set the caliper at 0.2 standard deviations of the logit of the estimated propensity score. The propensity score for each cohort was calculated using logistic regression based on all the confounders listed above. The covariates were included due to their theoretical association with postoperative pain. An absolute standardized mean difference less than or equal to 0.2 for each covariate was considered adequate for balanced matching. To compare the primary and secondary outcomes in the matched cohorts, we used the Wilcoxon signed rank test. A Historically – prior to initiation of SAP blocks for simple lumpectomies – the average perioperative opioid consumption [standard deviation] was 11.3 mg MEQ [5.9 mg]. If we assume clinical significance is reduction of opioids by 25%, we would require 65 patients in each cohort .There were 419 patients included in the analysis, in which 116 (27.7%) received a SAP block preoperatively in addition to our standard perioperative analgesia plan. All patients received surgical site infiltration with local anesthesia. The two cohorts studied were those who received SAP blocks and surgical site infiltration versus surgical site infiltration only. There were no differences in age, body mass index, ASA score, depression, anxiety, chronic pain, breast mass size, surgery laterality, medial location of mass, or primary anesthesia type between the cohorts (Table P = 0.33). The median [quartile] PACU pain score on the NRS scale in the surgical site infiltration only versus SAP block cohorts were 1  and 1.25 , respectively (P = 0.81). The median [quartile] maximum PACU pain score on the NRS scale in the surgical site infiltration only versus SAP block cohorts were 3  and 4 , respectively (P = 0.11). The median [quartile] PACU length of stay in the surgical site infiltration only versus SAP block cohorts were 80 minutes  and 78.5 minutes , respectively (P = 0.68).The median [quartile] perioperative opioid consumption in the surgical site infiltration only versus SAP block cohorts were 10 mg  and 10 mg , respectively  to perioperative opioid consumption Table .Table 2MP = 0.24). There was an association with body mass index (kg/m2) to perioperative opioid consumption .The model controlled for age, body mass index, ASA score, depression, anxiety, chronic pain, breast mass size, bilateral surgery, medial location of the mass, and primary anesthesia type. There was no statistically significant association with SAP block to perioperative opioid consumption . The median [quartile] PACU pain score on the NRS scale in the surgical site infiltration only versus SAP block cohorts were 1  and 1.25 , respectively (P = 0.89). The median [quartile] maximum PACU pain score on the NRS scale in the surgical site infiltration only versus SAP block cohorts were 2.5  and 4 , respectively (P = 0.09). The median [quartile] PACU length of stay in the surgical site infiltration only versus SAP block cohorts were 78 minutes  and 78.5 minutes , respectively (P = 0.75) (Fig. The median [quartile] perioperative opioid consumption in the surgical site infiltration only versus SAP block cohorts were 10 mg  and 10 mg , respectively (To our knowledge, this is the first study to investigate the potential benefit of regional anesthesia for outpatient simple lumpectomies without lymph node dissection. Although this was a retrospective study, this design allows for the inclusion of a much larger sample size compared to previous studies looking at SAP versus no regional anesthesia intervention. Furthermore, both cohorts were propensity matched controlling for a variety of factors associated with increased risk of perioperative pain such as age, BMI, and chronic pain , 4, 6. TWhile PVB has been established to be effective to provide superior and excellent analgesia for breast surgery , its useAs mentioned above, SAP blocks are mostly indicated for breast oncologic surgeries with expected pain in the distribution of the lateral cutaneous branches of the intercostal nerves, which is typically the lateral half of the breast . While tLimitations of this study include the retrospective nature of the study design, which limits conclusions about any relationship between regional interventions and outcomes as correlative instead of causative. Likewise, procedure documentation did not reflect superficial versus deep SAP technique and there was small variability among volume and local anesthetic concentrations used. One additional concern was the consistency of the local anesthetic that was given in the operating room by the various surgical teams. While this was not standardized, it always fell below the toxic limit and was very dilute compared to the regional block performed. Furthermore, there may be other confounders not included in our adjusted analysis that would be difficult to gather retrospectively. For definitive results, a large, appropriately powered, randomized controlled trial would need to be performed.This negative retrospective cohort study suggests that patients undergoing lumpectomies without lymph node involvement may not benefit from a preoperative SAP regional intervention when compared to local infiltration at the incision site by a surgeon. This may help limit unnecessary risks for patients moving forward.