Intraoperative blood loss was also significantly less in the IDP group than in the DP group . The PDQ-J score and preoperative NRS scores  did not differ significantly between groups. Less improvement in the NRS-BP (ΔNRS-BP) was observed in the DP group than in the IDP group (p < 0.05). Although pain improved after surgery in both groups, IDP surgery was advantageous in minimizing bleeding and preserving posterior support elements such as the facet joints, lamina, and paraspinal muscles. These findings suggest that this may have contributed to the higher rate of improvement in low back pain compared with DP surgery.The purpose of this study was to compare the short-term clinical outcomes between extreme lateral interbody fusion (XLIF) and minimally invasive surgery (MIS)–transforaminal interbody fusion (TLIF) in patients with degenerative spondylolisthesis with stenosis. One hundred-six patients were enrolled; 44 were treated with MIS–TLIF , and 62 were treated with XLIF . Perioperative indexes included operation time and intraoperative bleeding. Perioperative indexes preoperative and postoperative numeric rating scale (NRS) scores for low back pain (NRS-BP), leg pain (NRS-LP), and leg numbness (NRS-LN), and the preoperative score on the Japanese version of the painDETECT questionnaire (PDQ-J) were also assessed. The average follow-up period for the collection of NRS scores was 12.6 months. The operation time was significantly shorter in the IDP than in the DP group (109.9 ± 35.4 vs. 153.3 ± 50.9 min;  Since then, this technique has become a common approach to achieving interbody fusion3. Moreover, lateral lumbar interbody fusion (LLIF) is recognized as a minimally invasive surgical technique that allows access to the intervertebral disc space and vertebral bodies via a retroperitoneal transpsoas approach.Ozgur et al. published the first article in 2006 about surgery using the lateral transpsoas approach for interbody fusion6. In contrast to PLIF and TLIF, which often rely on direct decompression (DP) of neural elements such as removal of the ligamentum flavum, laminectomy, or facetectomy, LLIF can provide indirect decompression (IDP) when the large interbody cage ligament taxis technique is used7  and transforaminal interbody fusion (TLIF), complications such as incidental durotomy, nerve injury, massive blood loss, and epidural hematoma have also been documenteded7 Fig. . The gre9. Patients with symptomatic lumbar stenosis exhibit increased foraminal area, foraminal height, disc height, and central canal diameter after LLIF treatment. In addition, statistically, significant improvements have been reported on a visual analogue scale (VAS) scores for pain and quality of life after minimally invasive LLIF treatment10. However, few studies have compared the clinical outcomes in patients treated with the IDP and DP techniques. The purpose of this study was to compare the clinical outcomes, such as the changes in low back pain, leg pain, and leg numbness, between patients receiving IDP surgery using LLIF with extreme lateral interbody fusion  and those receiving DP surgery using minimally invasive surgery (MIS) involving TLIF (MIS–TLIF).Previous studies of LLIF have shown significant radiographic improvementsRetrospective data were collected and analyzed for 106 patients who met the inclusion/exclusion criteria. The average follow-up period for collecting NRS scores was 12.6 ± 5.6 months . The average age at the time of surgery was 68.8 years, and 60.4% of patients were men. Information about the two groups of patients is presented in Table p < 0.001). The operation times differed significantly between the single and dual positions: 92.8 and 128.0 min, respectively (p < 0.001).The percentages of patients who underwent MIS–TLIF were 41.5% (44 in the DP group) and 58.5% (62 in the IDP group) with XLIF and PPS fixation. We found no significant differences between groups for the mean age (66.9 ± 10.3 vs. 70.2 ± 8.1 years), sex , or the number of fused spine levels. The procedure involved one level in 33 patients and two levels in 11 patients in the DP group. In the IDP group, the procedure involved one level in 43 patients, two levels in 14 patients, and three levels in 5 patients; no patient underwent a procedure involving more than three levels. The operation time was significantly shorter in the IDP group than in the DP group . The preoperative and postoperative hemoglobin (Hb) levels did not differ significantly, but the change in Hb level was significantly smaller in the IDP group than in the DP group.The intraoperative blood loss was significantly less in the IDP group than in the DP group .Among all patients with low back pain and/or leg pain, 54 (50.9%) had nociceptive pain, 17 (16.0%) had neuropathic pain, and 35 (33.0%) had an unclear type of pain (mixed pain) at their preoperative examination Table . The PDQp = 0.940). A similar tendency was observed for the NRS-LN and NRS-LP scores , leg pain (mean NRS-LB of 6.8 ± 2.5), or leg numbness (mean NRS-LN of 6.3 ± 3.0), but the scores for these components did not differ significantly between the two groups. The postoperative NRS-BP scores at the final follow-up were 3.1 ± 3.0 and 2.6 ± 2.8 for the DP and IDP groups, respectively, but did not differ significantly (p < 0.05). However, the ΔNRS-LP and ΔNRS-LN scores did not differ significantly between the two groups  differed significantly between the two groups: 3.6 ± 3.7 and 2.3 ± 3.3 in the DP and IDP groups, respectively  and XLIF (20 patients), with a follow up of 1 year in terms of clinical results and radiological change. Postoperative clinical results were equally favorable for both procedures. However, XLIF had significantly improved correction of disc height compared to the mini-open TLIF13.However, few studies have compared LLIF with the other procedures, and further studies are needed to compare the results of LLIF with those of traditional lumbar interbody fusion approaches. Sembrano et al. compared ALIF, LLIF, TLIF, and posterior spinal fusion in 6- week radiographic outcomes. They concluded that LLIF could improve sagittal contour and other interbody fusion approaches and is superior to posterior fusion in disc height restoration14. Phillips et al. also evaluated 82 of 107 patients with degenerative scoliosis who were available for the 24-month follow-up and found that the VAS scores for back and leg improved significantly from before the operation to the 24-month follow-up. The mean VAS score was reduced by half within five months after the surgery and remained constant thereafter. The mean improvement in VAS scores from before to 24 months after the operation were 3.4 for back pain and 3.5 for leg pain15. Based on this background, our study compared the clinical results of patients who received DP or IDP. We focused on the NRS scores. The patients who underwent IDP surgery showed significantly higher low back pain, leg pain, and leg numbness scores at the final follow-up compared with those who underwent DP surgery, although no differences were found about 12 months after surgery. However, a comparison of the improvement in NRS scores between the two groups showed that the IDP group exhibited more significant improvement in low back pain, possibly because invasive surgery was not performed, which would have limited the stress on the posterior support elements such as the facet joints, lamina, and paraspinal muscles.Significant improvement was noted in clinical outcomes including VAS. In a previous prospective analysis of postoperative pain progression in 600 patients treated with LLIF for degenerative spinal conditions, Rodgers et al. showed that the average VAS score decreased from 8.8 to 3.1 after LLIF, immediate improvement of 65%16. Salzmann et al.17 also reported rates of early postoperative anterior thigh pain and sensory and motor deficits in a cohort of 451 patients who underwent LLIF were 38.5%, 38.0%, and 23.9%, respectively. The authors also found that their percentage have decreased over time. According to a systemic review that compared the complications between MIS–TLIF and LLIF, both surgeries have acceptable complication profiles, although LLIF has an overall significantly higher complication rate than MIS–TLIF (31.4% vs. 19.2%). For specific complications, LLIF has higher rates of sensory as well as temporary and permanent neurological symptoms but does not have a significantly lower risk of intraoperative complications (1.93% for LLIF vs. 3.57% for MIS–TLIF)11. In our study, transient neurological complications such as hip flexion weakness, anterior thigh pain, and sensory and motor deficits were the most common and accounted for 17.7% of all complications. This percentage is similar to that reported previously. There have been several reports of the causes of these symptoms19. We believe that preventing blind dissection of the psoas muscle and minimizing the operation time required for LLIF may be effective for preventing these neurological complications10.On the other hand, despite its overall success, LLIF has been reported to have some unique complications, such as hip flexion deficit and lumbar plexus related motor deficits. Tomeh et al. reported that 27.5% of 102 patients who underwent LLIF experienced postoperative hip flexion weakness, which was transient and typically resolved within the first two weeks after surgeryThe present study has limitations such as its retrospective design, small sample size, short follow-up, and lack of multiple-factor analysis. The longer-term clinical data are necessary for determining pseudarthrosis rates. We also think that the surgical indications for some degenerative diseases should be strictly defined in future prospective studies. The L5/S1 level is not accessible for an LLIF, and the levels at L3/4 and above are typically better treated by an LLIF. Therefore, evaluation is the most important at the L4/5 level. If the number of patients increases, we would like to investigate procedures using only at the L4/5 level. Further prospective randomized clinical trials are needed to investigate whether MIS surgery is advantageous for improving postoperative pain.To our knowledge, this is the first study to focus on the changes in low back pain, leg pain, and leg numbness from before to after DP (MIS–TLIF) and IDP (XLIF) surgery to treat patients with DS with stenosis. The severe complications' rate might be inferior in the IDP compared with the DP surgery.The estimated blood loss was lower, and the operation time was shorter in the IDP than in the DP group. Both groups exhibited improved low back pain, leg pain, and leg numbness, but the IDP group had a more significant improvement in low back pain than the DP group. Differences in the invasiveness of the procedures involving the posterior support elements, such as the facet joints, lamina, and paraspinal muscles, may be responsible for the differences between groups. However, more studies with longer follow-up are necessary to evaluate the IDP approach's theoretical benefit and assess whether the results of IDP are superior and durable as the ones achieved by the DP approach.This study was approved by the Institutional Review Board of Tokai University School of Medicine, the House Clinical Study Committee, and the Profit Reciprocity Committee, and all of the methods were carried out in accordance with relevant guidelines and regulations. Because this study was retrospective, informed consent was not obtained from each patient and the requirement for informed consent was waived .We conducted this retrospective single-center study by reviewing the surgical and clinical data of patients diagnosed with degenerative spondylolisthesis (DS) with restenosis who underwent lumbar decompression and surgical intervertebral fusion.The inclusion criteria were age > 18 years, lumbar spinal canal stenosis and lumbar DS, and undergoing a combined operation (IDP) using LLIF or MIS–TLIF at a single institute from January 2016 to October 2019. We started performing IDP using LLIF in this institution in 2016; before that, only MIS–TLIF was performed.20.All patients were diagnosed based on a detailed history, neurological examination, radiographic examination, myelography, computed tomography after myelography, and/or magnetic resonance imaging (MRI). The main indication was neurogenic claudication caused by central or foraminal spinal stenosis. The conditions for a diagnosis of spondylolisthesis and the inclusion criteria for fusion surgery were > 5% slip of the lumbar vertebra in a neutral position or > 3-mm translation between flexion and extension positions radiographic evaluation. The operating surgeons recorded the location of stenosis based on their evaluation of the preoperative imaging studies. The exclusion criteria included previous lumbar spinal surgery at the same level or receipt of combined procedures, including direct posterior decompression and posterior lumbar fusionThe patients were categorized into two groups based on the operative procedure: the DP and IDP groups. Data were collected retrospectively and included demographics, operative details, the preoperative Japanese version of the painDETECT questionnaire (PDQ-J) score, numerical rating scale (NRS) scores, and postoperative neurological complications.Patients in the DP group who received the MIS–TLIF were placed in the prone position. The facet joints and the ligamentum flavum were removed using a laminectomy rongeur, and the traversing nerve roots, exiting nerve roots, and lateral edge of the dura were exposed and decompressed. The annulus was incised, and a complete discectomy was performed. After confirmation of the spacer size, a polyether ether ketone cage filled with autologous cancellous bone was inserted accurately. The percutaneous pedicle screws (PPSs) were placed after the decompression. A bent rod was placed to connect the PPSs, and the intervertebral space was moderately compressed to ensure that the cage was very solid.21. After the LLIF procedure, the patient was repositioned in the prone position  or the lateral decubitus position (single position), and the PPS was inserted. Posterior lumbar fixation using PPSs was then performed using fluoroscopy or an O-arm-based navigation system. The reference frame placed at the cranial spinous process was used for navigation.All patients in the IDP group who received XLIF and PPS fixation underwent MIS–LLIF surgery performed using the XLIF technique. The XLIF procedure has been described previously22 was used to identify the presence of neuropathic pain. The final score ranges from − 1 to 38 and indicates the likelihood of a neuropathic component. A score of ≤ 12 indicates a low likelihood of a neuropathic component, and a score of 19 suggests a high likelihood of a neuropathic component. The cutoff values for categorizing the type of pain based on the PDQ neuropathic pain-screening questionnaire scores were as follows: nociceptive pain, 0–12; unclear type of pain (mixed nociceptive and neuropathic pain), 13–18; and neuropathic pain, 19–38. The PDQ-J has been validated and has good reliability and validity, according to a study by Matsubayashi et al.23.The PDQ established by Freynhagen et al.NRS scores were recorded using a 0–10 scale with 0 = no pain or numbness and 10 = the worst pain imaginable or numbness and were used to evaluate low back pain (NRS-BP), leg pain (NRS-LP), and leg numbness (NRS-LN). For all participants who were followed, data were obtained preoperatively and at the time of the final follow-up to complete the clinical evaluation.p value < 0.05 was considered statistically significant21.All data are expressed as mean ± standard deviation. Univariate differences between DP and IDP groups were assessed using independent-sample t-tests or the Mann–Whitney U test for data that were not normally distributed. The correlations between the PDQ-J and NRS scores were analyzed with the spearman’s product-moment correlation coefficient. All statistical analyses were performed with SPSS version 20.0 , and a


To estimate the resource gap in the polymerase chain reaction (PCR) monitoring for patients with chronic myeloid leukemia (CML) in low- and middle-income countries (LMICs).IV system. We included costs of GeneXpert® instruments, uninterrupted power supplies, warranties, calibration kits, test cartridges, and shipping. We calculated the country-specific monetary gap in PCR monitoring, stratified by country priority defined as the availability of tyrosine kinase inhibitors (TKIs) through The Max Foundation initiatives.We developed a model of demand and supply of PCR monitoring of CML patients in 60 LMICs. PCR testing was assumed to use Cepheid’s GeneXpert® The 5-year gap in PCR monitoring was $29.1 million across all countries, 22% ($6.4 million) in countries with all five TKIs available, 20% ($5.7 million) in countries with four TKIs available, 50% ($14.5 million) in countries with three TKIs available, 8% ($2.2 million) in countries with two TKIs available, and 1% ($0.3 million) in countries with one TKI available. The gap was highest in South Asia  and lowest in Latin America . Excluding labor costs, the bulk of the resource needs  were for procurement of BCR-ABL cartridges.Removing the 5-year gap in PCR monitoring capacity for CML in LMICs will require the mobilization of significant resources and will likely lead to better treatment outcomes and reduced treatment costs through optimization of treatment, discontinuation of therapy in appropriate patients, and facilitation of clinical research. Development of streamlined monitoring guidelines for resource-limited countries should be considered. The advent of tyrosine kinase inhibitors (TKIs) has transformed chronic myeloid leukemia (CML) from a near universally fatal disease into a chronic condition. There are now five TKIs approved for use in newly diagnosed CML in the USA, the pioneering TKI imatinib, and the “second generation” TKIs dasatinib, nilotinib, ponatinib, and bosutinib. All have similarly impressive results and CML patients now experience life expectancy near that of the age matched general population .CML is caused by the genetic juxtaposition of the BCR gene from chromosome 22 with the tyrosine kinase domains of the ABL gene from chromosome 9. This unique gene fusion creates the fusion BCR-ABL1 mRNA, which is the target for polymerase chain reaction (PCR) diagnostic and monitoring assays. The protein product of BCR-ABL translocation drives the pathogenesis of CML and is the target of the TKIs.Peripheral blood can be used for BCR-ABL monitoring, rather than bone marrow, and guidelines of the European Leukemia Network (ELN) and the National Cancer Care Network (NCCN) include frequent monitoring as a way to track response. In general, both guidelines call for every 3-month peripheral blood PCR testing for BCR-ABL1 , 3. TreaConventional PCR testing is complicated and labor intensive, demanding trained personnel, many chemicals, and expensive equipment. Quality control is essential to obtain and maintain proper sensitivity and specificity of the assay, and this requires technical and methodological expertise and training. The GeneXpert system from Cepheid is a cartridge-based system that requires minimal hands on sample preparation and is ideal for point of care, real-time assays . The sysTo bring TKIs to LMICs, The Max Foundation partnered with Novartis to launch the Glivec® International Patient Assistance Program (GIPAP), an innovative access model that made Novartis’ breakthrough oral TKI therapy, Glivec® (imatinib) available to patients at no cost. Glivec was made available to patients in selected LMICs around the world who met specific program criteria, such as confirmed indication for the medication, presence of partner institutions for diagnosis and management, and tax waivers for donated TKIs by governments among other criteria . The MaxIn the early years of the program, BCR-ABL1 testing was largely performed by shipping blood to outside centers, a procedure that was costly, time-consuming, and inherently unscalable. Recognizing the critically important role that point-of-care systems play in the diagnosis and monitoring of patients in resource poor settings, The Max Foundation developed a collaboration with Cepheid to increase access to instruments and tests in more than 60 LMICs. Cepheid provided the GeneXpert® System and Xpert® BCR-ABL Monitor Assays (through The Max Foundation) to public sector end users at a preferential price in order to decrease barriers to access due to cost. The dramatic increases in monitoring meant disease resistance could be detected, so that TKI options to treat resistance could be initiated as needed. The Max Foundation began partnering with four other leading pharmaceutical companies to bridge access to all five TKIs available on the market for the treatment of CML today. As a result of these efforts, selected patients in thirty of the world’s lowest income economies have access to all available treatment options through The Max Foundation’s Max Access Solutions.Recently, GIPAP evolved into a new partnership model between Novartis and The Max Foundation, CMLPath to Care™. CMLPath to Care™ differs from the GIPAP program in that The Max Foundation assumes from Novartis the responsibility for delivering treatment to patients. The Max Foundation, under the umbrella of Max Access Solutions (MAS), manages the entire supply chain, while strengthening interactions with local stakeholders and providing hands-on, local patient support .The establishment of collaborations with developers of all TKIs for the treatment of CML enables The Max Foundation to respond to health care providers’ requests for second and third line treatment in many of the lowest income economies in the world. Yet, despite the preferential pricing available for Cepheid products, access to PCR remains one of the most pervasive barriers to achieving optimal clinical outcomes. Without adequate monitoring, physicians are unable to make timely and appropriate clinical decisions that help patients with CML achieve a deep response to available treatments. This analysis was performed to assess the resources needed to close the 5-year gap in PCR monitoring capacity for CML patients covered by programs supported by the Max Foundation in countries where The Max Foundation currently operates.We developed a Microsoft Excel-based demand, supply, and forecast model for the monitoring of CML patients in a selected group of countries and a selected group of patients in those countries covered by access initiatives and using preferential prices available through The Max Foundation for the GeneXpert® system. The gap in PCR capacity for monitoring was estimated as the difference between current/projected demand and current/projected supply over a 5-year time horizon from 2017 to 2021.We estimated effective demand as the number of patients that would qualify for access to imatinib treatment in each country i.e. patients who would qualify for treatment under The Max Foundation’s access initiatives. This is differentiated from actual demand based on the burden of CML in each country, a burden that is substantially higher than is covered by The Max Foundation’s access initiatives . We estiCountries were categorized for the analysis by availability of one or more of the five TKIs to maximize the potential utility of PCR monitoring results by physicians. Countries were excluded from the analysis if they were known to have appropriate access to PCR and if they did not have preferential pricing for GeneXpert PCR through Cepheid.We estimated future demand for PCR monitoring in The Max Foundation programs based on historical patient data from The Max Foundation. We restricted our demand estimates to patients who would qualify for Max Access Solutions and The Max Foundation’s preferential pricing agreement with Cepheid. Of the 67 countries covered by Max Access Solutions and The Max Foundation’s preferential pricing agreement with Cepheid, 56 had 12 years of historical data, four countries had 11 years of historical data, two countries had 10 years of historical data, three countries had 8 years of historical data, one country had 7 years of historical data, and one country had 4 years of historical data. In our final analysis, we included 60 countries after excluding Angola, Barbados, Botswana, Costa Rica, Guinea, Pakistan, and Panama because they did not have patients currently receiving treatment through The Max Foundation programs. For countries with non-linear historical trends, the earlier, nonlinear years were truncated from the analysis. Estimates of future demand, estimated as number of patients, were calculated using a simple linear ordinary-least-squares regression.Data from The Max Foundation demonstrate that the introduction of GeneXpert® affects the demand for CML treatment, and consequently, the demand for PCR monitoring in a country. Therefore, based on consensus among the study team members, we made the assumption and modeled that the rate of growth doubled (2x) after introduction of GeneXpert®, e.g., a country that historically gained 10 additional patients per year before GeneXpert® introduction, was modeled, after introduction, as gaining 20 additional patients per year.The quantity of required GeneXpert® instruments and GeneXpert® cartridges for purposes of gap estimation was based on a number of factors: current demand, anticipated future demand, current number of GeneXpert® instruments in place by country, geographic demand distribution of patients and testing facilities, and expert opinion in the form of NCCN and ELN guidelines, as described above.We estimated the following PCR monitoring-related costs in year 1: (1) GeneXpert® instruments, (2) uninterrupted power supplies (UPS), (3) warranties, (4) calibration kits, (5) test cartridges, and (6) shipping for instruments and test cartridges. During years two to five, the following PCR monitoring-related costs were included: (1) calibration kits, (2) test cartridges, and (3) shipping costs for cartridges. Costs did not include labor to perform the assay. Costs were obtained from The Max Foundation records and estimated in 2017 $US. Future costs were discounted to 2017 $US at a rate of 3%.Our analysis differentiated between fixed costs in the first year  and variable costs . Costs for the instruments, warranty, calibration kits, and UPSs, were established by contract , calculating the resulting mean of many draws, and then summing each component average into an overall cost for each country for each year. The means of the normal distributions from which we drew were set equal to the deterministic cost values. The upper and lower 95% intervals were set to ± 50% of the means. The presented estimates were derived from 1,000 iterations.The total 5-year gap in PCR monitoring capacity for each country, categorized by TKI access, is presented in Table The distribution of the total PCR monitoring capacity gap by TKI access level Table  was as fIn those countries where all five TKIs are currently available through The Max Foundation programs, the 5-year gap ranged from $31,681 in Sierra Leone to $1,561,298 in Nepal. In the countries with four TKIs available, the gap ranged from $29,515 in Central Africa Republic to $1,363,279 in Sudan. In the countries with three TKIs available, the gap ranged from $31,144 in Seychelles to $13,238,674 in India. In the countries with two TKIs available, the gap ranged from $35,980 in The Bahamas to $1,422,762 in Vietnam. In the countries with a single TKI available through Max programs, the gap ranged from $36,238 in Ecuador to $68,943 in Gabon.The distribution of the total PCR monitoring capacity gap by region was as follows Table : 52%  for cartridges, 7%  for shipping, 3%  for GeneXpert® machines, 2%  for warranties, 1%  for calibration kits, and 0.2%  for UPSs  cost of $50, single-test cartridges are still costly, particularly in resource-poor settings. Although CML is a relatively rare disease worldwide, a buy-down approach consisting of an up-front, pre-purchase of Xpert® cartridges at higher volumes and reduced prices might further reduce costs. A similar approach was employed by the Bill and Melinda Gates Foundation, the United States President’s Emergency Plan for AIDS Relief (PEPFAR), the United States Agency for International Development (USAID), and Unitaid , 11.A limitation of our analysis is that we used estimates of the burden of disease by country based on the number of CML patients enrolled in GIPAP and Max Access Solutions from 2002 to 2017. This is an underestimate of the true gap based on burden of disease estimates obtained from epidemiological data . There aRemoving the gap in PCR monitoring capacity for CML can help improve health outcomes. While quantifying the health outcomes benefit was beyond the scope of this analysis, we expect that removing the gap in PCR diagnostic capacity would increase the demand for CML care, both within the access initiatives available through The Max Foundation and in general health services. Future studies might consider quantifying the health outcomes benefits in terms of quality-adjusted life-years gained or disability-adjusted life-years averted using state-transition (Markov) models as in multiple economic evaluations of TKIs –16.NCCN and ELN monitoring guidelines are based on monitoring intervals used in TKI clinical trials, and thus it is not clear what optimal testing intervals actually are. For example, optimal design might include how long a patient has been on a TKI, and the kinetics of their BCR-ABL1 decline, rather than a simplistic every 3 months rule. Thus, revisiting guidelines with limited resources in mind may allow for a CML monitoring scheduled tailored to the LMIC setting, optimizing the benefits of frequent monitoring without sacrificing patient outcomes.By treating thousands of patients since 2001 in eligible countries, The Max Foundation’s access programs have added thousands of life-years and improved the quality of life of thousands of people living with CML. Removing the 5-year gap in PCR monitoring capacity for CML in these countries will require the mobilization of significant resources and will likely lead to better treatment outcomes and reduced treatment costs through optimization of treatment, discontinuation of therapy in appropriate patients, and facilitation of clinical research.


There are a number of nonsurgical modalities used by athletes in attempts to improve performance or prevent, treat, and rehabilitate musculoskeletal injuries. A concise review of available evidence on common nonsurgical modalities used today is necessary so that practitioners may appropriately counsel patients.A comprehensive review of relevant publications regarding Kinesio taping, sports massage therapy, and acupuncture from 2006 through 2019 was completed using PubMed and Google Scholar.There have been numerous investigations evaluating the efficacy of nonsurgical modalities for a myriad of musculoskeletal conditions. There is some low level evidence to suggest the use of Kinesio tape for athletes with acute shoulder symptoms and acupuncture for carpal tunnel syndrome and as an adjunct treatment for low back pain. There is a need for higher quality research to better elucidate the effect of sports massage therapy on sports performance, recovery, and musculoskeletal conditions in general.Nonsurgical modalities are low-cost treatment strategies with very few reported adverse outcomes that will likely continue to increase in popularity. High-quality studies are needed to effectively evaluate these treatments, so that care providers can provide appropriate guidance based on evidence-based medicine. The sports medicine specialist enjoys a unique role in the nonsurgical and surgical care of active patients of all skill levels. However, various nonsurgical modalities represent a notable element of sports medicine and musculoskeletal care that is not traditionally taught during orthopaedic training. The increasing use of such modalities merits a review of available evidence to appropriately assess their efficacy and safety, so that clinicians are able to make informed decisions in the care of patients requesting such therapy. In part 1 of this two-part series, we analyze Kinesio taping, sports massage therapy (SMT), and acupuncture. Part 2 will discuss cupping and blood flow restriction training.2 According to the manufacturer, KT has specific properties that make it more effective than traditional athletic tape. From a functional standpoint, KT can stretch up to 140% to 160% of its original length and recoil back to apply a tensile force to the skin.3 It can also be worn longer and stick better to skin than traditional tape during athletic events because of its water resistance and breathability.4 Physiologically, KT purportedly improves proprioceptive signals to the brain and increases blood and lymphatic flow by lifting the skin off the underlying fascia. KT is also hypothesized to decrease pain by diminishing input from afferent nerve fibers and reducing pressure on subcutaneous nociceptors.6 Below we review the available evidence for the use of KT to investigate whether these claims provide a clinical benefit.Athletic taping is a common practice, thought to improve proprioception and muscular function by providing support and protection during active movement. Kinesio tape (KT) was developed in the 1970s by chiropractor Dr. Kenso Kase, and it has gained prominence in popular culture and athletics. Its use was especially bolstered during the 2008 Olympics when the tape was donated to 58 nations and worn by many high-profile athletes.78910 Among these, Thelen et al7 compared the short-term effects of KT and sham taping for rotator cuff tendinitis and impingement. The authors found that KT markedly improved pain-free shoulder range of motion (ROM) in abduction after immediate application, but not after 3 and 6 days. No differences in pain or disability scores were identified. Hsu et al8, in the only analysis of injured athletes, done a kinematic investigation in 17 baseball players with shoulder impingement comparing KT to athletic tape. KT increased the activity of the lower part of the trapezius muscle as measured by EMG immediately after taping. The clinical significance of this finding is unknown. Finally, Gonzalez-Iglesias et al9 investigated 41 patients with cervical neck pain and found a notable improvement in pain and ROM immediately after KT placement and after 24 hours.There are a limited number of high-quality clinical trials published evaluating KT. To the best of our knowledge, the first systematic review of KT was done in 2010 and included three randomized controlled trials (RCTs) comparing KT with sham taping for various musculoskeletal conditions.10Although the above three trials did identify some statistical significance results, perhaps pointing toward increasing the ROM of the shoulder and cervical spine and decreased pain within the first 24 hours of KT placement, the data have notable limitations. For instance, there was a lack of blinding for therapists providing the intervention and doing outcome measurements. More importantly, no trial showed any sustained benefit of taping given the short follow-up periods, and all statistically notable differences identified were so small that authors questioned their clinical significance. As such, this systematic review concluded that there was not sufficient evidence to support KT.2 published a second meta-analysis analyzing KT. Of included articles that investigated KTs role in increasing strength, Chang et al. showed no difference in maximal grip strength, while Hsu et al and Lee et al both showed an increase in maximal grip strength.12 Owing to these conflicting results, the meta-analysis could make no final recommendations regarding the use of KT for increasing grip strength. Regarding quadriceps strength, Vithoulk et al showed that KT in healthy women could increase quadriceps torque during eccentric exercise compared with no taping or sham taping, while Fu et al found that KT could improve peak torque during concentric quadriceps contractions.14 As such, Williams et al concluded that there is some evidence to suggest KT may a small benefit on patient strength. Among other findings, the authors concluded that there was no evidence to support KT use for ankle pain or proprioception, and that overall, further research was required to justify KT's use among a clinical population.4In 2012, Williams et al15 Parreira Pdo et al16 compared a 4-week course of KT versus sham taping and found no differences in pain, disability, or global perceived effect at 12 weeks. Kachanathu et al. and Bae et al also showed no differences in pain or disability between cohorts either treated with KT in addition to traditional physical therapy versus physical therapy alone for 4 weeks or 12 weeks, respectively.18 Castro-Sánchez et al19 done 1 application of KT versus sham KT for a single week and reported a notable reduction in pain in their KT cohort at 1 and 4 weeks of follow-up. And, finally, Paoloni et al20 showed no difference in pain or disability scores after 4 weeks of treatment with either KT alone, KT plus therapeutic exercise, or exercise alone. Nelson agrees with previous KT meta-analyses in that KT may provide a transient, although perhaps not clinically significant, reduction in pain, and perhaps an improvement in endurance after 4 weeks of KT, but once again points out the lack of high-quality evidence to make a strong recommendation for its use. Finally, in an RCT, Macedo et al21 reported KT applied with and without tension markedly decreased low back pain at 3 days, but not 10 days, after application compared with those without KT. Macedo et al also found a notable reduction in disability through 10 days in patients treated with KT compared with those without. These findings support the meta-analysis by Nelson15 in which the effectiveness of KT in reducing long-term low back pain is questionable.KT has also been investigated as a treatment for chronic low back pain as reviewed in a meta-analysis of five studies by Nelson.22 evaluated the immediate effects of KT within 1 hour of application on elderly patients with radiographically confirmed OA. The authors found that compared with the sham cohort, patients receiving KT experienced notable improvements in pain, ROM, and proprioception of the affected knee. Kocyigit et al23 compared patients who wore KT and sham KT continuously for 12 days. The authors found that both KT and sham KT improved pain, and that both groups had an increase in functional performance, but that real KT was not superior to sham KT. Similarly, Wageck et al24 evaluated knee concentric muscle strength and pain in adults with OA treated with KT or sham tape. The authors did not find an improvement or difference in knee strength or pain through the 19-day follow-up period. It should also be noted that the above studies did not differentiate the severity of OA being treated radiographically by the Kellen Lawrence scale.KT has also been studied for the treatment of osteoarthritis (OA) in two RCTs comparing KT with sham KT. Cho et alAlthough KT has been recently popularized and is widely used, there is a lack of convincing and well-designed evidence to support its use for musculoskeletal conditions. There may be a small immediate effect of KT on pain and ROM in some joints, but further high-quality studies are needed to rationalize its use for patients. There is some evidence that suggests it may be reasonable to apply KT in the athletic patient with shoulder symptoms in the immediate preactivity/sport setting. Given that no studies have ever reported an adverse outcome associated with KT, its safety, affordability, and popularity may continue to make in an attractive option to patients.25 The practice of SMT was first offered as a core medical service to the US Olympic team at the 1996 Summer Olympic Games in Atlanta and is now regularly used by many professional, Olympic, and collegiate athletes to address the varying physical sequelae of athletic competition.26Therapeutic massage is the practice of manipulating muscles and limbs to ease tension and reduce pain. Massage therapy dates back thousands of years, with the first written records linked to ancient Chinese and Egyptian culture where oils and herbs were used as an adjuvant to address muscle pain. The practice of therapeutic sports massage developed alongside athletics in ancient China where it was used by Taoist priests for the treatment of practitioners of Kung Fu, as well as in ancient Greece in the care of Greek Olympians. Today, massage is widely practiced and taught in Chinese hospitals and medical schools and originally gained popularity in the United States in the 19th century on its introduction by two New York physicians.There is a myriad of types and styles of massage that use several pieces of fundamental equipment depending on the particular technique. Specialized padded massage tables and ergonomic chairs allow for appropriate positioning while U-shaped head supports enable an ease of breathing as the athlete lies prone. Low-cost, easily accessible equipment, such as foam rollers, is also used for deep muscle massages before and after workout.28 Physical therapists, athletic trainers, and certified massage therapists are the practitioners commonly doing SMT in the athletic arena with limited supporting evidence. A comprehensive meta-analysis of massage therapy research conducted by researchers at the University of Illinois at Urbana-Champaign evaluated several variables and factors from 37 studies which included gate control theory of pain reduction, promotion of parasympathetic activity, influence of body chemistry, mechanical effects, promotion of restorative sleep, and interpersonal attention. The authors concluded that the current body of evidence “supports the general conclusion that massage therapy is effective.”29SMT has been proposed as a means to help prepare athletes for competition through enhancement of athletic performance, as a treatment approach to aid in recovery after competition, and as a direct intervention for sports-related musculoskeletal injuries.30–32 Strength is another key component to the overall health and success of high-level athletes. The assessment of therapeutic massage on power grip strength in a pre-test and post-test study design by Brooks et al33 reported superiority in postexercise grip performance in those patients having undergone massage intervention. Therefore, the authors conclude that applying massage for 5 minutes shortly after fatiguing exercises is beneficial. An additional investigation by Mancinelli et al34 evaluated the effects of SMT on female collegiate athletes done at the beginning of the basketball and volleyball seasons. The study consisted of 22 National Collegiate Athletic Association Division-I women's basketball or volleyball players who underwent a 17-minute massage. The authors reported that the massage intervention markedly increased the athlete's vertical jump and decreased their perceived soreness. Moran et al.35 conducted a randomized, counterbalanced, repeated measures experiment to investigate the effect of precompetition massage compared with a traditional warm-up, massage and warm-up, and ultrasonography control on 60-meter sprint times in 17 NCAA track and field athletes. The authors found no notable differences between any of the interventions with respect to sprinter speed or acceleration. Macgregor et al36 conducted a randomized, counterbalanced, repeated-measures experiment to assess muscular efficiency and flexibility in 16 males after foam rolling compared with no intervention controls. The authors found that maximal voluntary contraction of muscles was markedly greater in patients using the foam roll for three days compared with the control group, although range of motion was not markedly different. Conversely, Hodgson et al37 conducted an RCT comparing ROM and jump performance of active students who foam rolled three times a week, six times a week, or not at all. The authors found no consistent training-induced changes from foam rolling.Proper flexibility and strength are vital factors with regard to injury prevention and overall performance in competitive athletes. Studies on the effect of SMT on flexibility have demonstrated positive short-term outcomes with multiple studies evaluating hamstring flexibility in physically active young men and female field hockey players receiving a classic massage and deep tissue massage.38 However, overall shoulder function was not analyzed. An additional meta-analysis consisting of 12 RCTs evaluating the impact of massage therapy on neck and shoulder pain suggests immediate positive effects of massage therapy on both shoulder and neck pain with short-term positive effects for shoulder pain only. However, functional status of the shoulder was not found to be markedly affected by massage therapy.39In attempt to examine specific pathologies, a randomized single-blinded study evaluating the therapeutic effects of massage on pain, muscle tension, and anxiety in patients with scapulothoracic pathology reported statistically notable improvement in pain intensity and muscle tension.40 The authors found an exercise program to be more effective than both pulsed ultrasonography and transverse friction massage immediately after treatment and at 3 months of follow-up.40 In further evaluation of the effect of therapeutic massage on musculoskeletal disorders, Bervoets et al41 done a systematic review of 26 studies consisting of 2,565 patients. The authors concluded that therapeutic massage reduced pain and improved function compared with no treatment for some musculoskeletal conditions. In addition, a comprehensive review of the literature broadly examining the effect of massage on sports performance was conducted with the inclusion of studies investigating the use of massage in all facets of athletic care and concluded that “poor appreciation exists for the appropriate clinical use of sports massage” with additional studies required to further examine the “physiological and psychological effects of sports massage.”42Associated pathology and disorders of the knee are also common findings in athletes for which friction massage and several nonsurgical modalities have been compared. Stasinopoulos et al evaluated the effectiveness of transverse friction massage compared with a focused exercise program and pulsed ultrasonography in a cohort of patients in their 20 and 30 seconds with patellar tendinopathy.Despite multiple independent studies and subsequent meta-analyses, there is a strong need for higher quality research examining the efficacy and acceptability of massage therapies in the athletic patient population to determine a more direct correlation between the effects of SMT on sports performance and recovery, as well musculoskeletal conditions in general.43 A recent survey by the National Institute of Health in the United States found that more than three million Americans had undergone treatment with acupuncture at least once in the previous year.44 Traditional acupuncture involves a specific pattern of placing needles at certain locations on the body, called meridians. In traditional teachings, the goal of acupuncture is to balance yin and yang forces within the body, yin being the cold and slow force and yang the hot and excited. A blockage of the flow of these energies, or qi, was believed to be a source of pain and pathology. Therefore, it was believed that placing needles along meridians of the body would unblock that flow and restore balance. In a more Western physiological sense, it is believed that acupuncture works by stimulating trigger points in various muscle groups promoting the release of endogenous hormones, such as endomorphin, encephalin, and serotonin, and creating an analgesic effect.45 Although the exact mechanism by which acupuncture exerts its effects continues to be debated, its practice has been evaluated clinically for many different musculoskeletal applications.Acupuncture is a form of complementary and alternative medicine used by many patients to treat a variety of disorders. Acupuncture originated in China over 2,000 years ago, and its popularity in the West has increased.46 The authors concluded that compared with no treatment, acupuncture can provide pain relief and functional improvement at short-term follow-up. When compared with sham acupuncture, acupuncture showed some pain relief in short term but not long-term follow-up and no improvement in function. When compared with other alternative treatments (such as massage), acupuncture showed no improvement in pain or function, but when added to conventional treatments , acupuncture improved pain scores and functional outcomes compared with conventional therapies alone. Other reviews are less enthusiastic, stating there is no evidence to suggest that acupuncture provides analgesia for the neck or back compared with placebo or sham treatment,47–49 while others claim it may be better than placebo, but no better than other treatment modalities such as spinal manipulation or massage.50For chronic low back pain, there are several recent systematic reviews and meta-analyses investigating the efficacy of acupuncture. For instance, a 2005 Cochrane review included 22 RCTs evaluating acupuncture.43 in 2008. The authors reviewed 19 RCTs and concluded that acupuncture was not superior to any treatment for immediate and short-term pain relief, or immediate functional improvement, but was superior to no treatment for short-term functional outcomes. However, there was good evidence that acupuncture, when added as an adjunct to other treatments such as NSAIDs, non-narcotic analgesics, mud packs, infrared heat therapy, back care education, ergonomics, and behavioral modification, improved patient pain symptoms and functional outcomes compared with those interventions alone.The most current systematic review of the literature was done by Ammendolia et al51 In the United States, the American College of Physicians and the American Pain Society recommend that for patients who have low back pain that is refractory to conventional medical care and exercise, adjunct treatments may be used. Acupuncture has a “weak recommendation” because of the availability of only moderate-quality evidence.52In light of the available data, several large bodies have recently released recommendations regarding the use of acupuncture for back pain. The European guidelines do not recommend acupuncture for the treatment of chronic, nonspecific low back pain.53 15 RCTs were reviewed for various ailments of the extremity. For carpal tunnel syndrome, it was found that there was a notable improvement in patient-reported symptoms such as pain and numbness with traditional acupuncture when compared with patients receiving prednisolone injections, sham acupuncture, night splinting, and vitamin B supplements.54–56 The authors point out that these statistically notable results may lack clinical significance because the differences were small. Acupuncture showed no improvement in pain in patients with recent-onset plantar fasciitis compared with placebo.57 Finally, there was no difference in patient-reported pain at 5 months in patients with patellofemoral pain syndrome treated with acupuncture compared with no treatment.58Acupuncture has also been described for treatment of musculoskeletal problems of the upper and lower extremity. In a recent review by Cox et al,59 Green et al59 showed that acupuncture did no better than placebo in relieving pain or improving ROM in patients with rotator cuff disease. There is evidence that acupuncture, when added to exercise is more effective in increasing ROM and decreasing pain in patients with adhesive capsulitis when compared with acupuncture alone.60 Acupuncture was equivalent to ultrasonography treatment for pain relief in patients with impingement.61 For nonspecific shoulder pain, acupuncture showed statistically, but not clinically notable reduction in pain after 3 months of treatment.62 Green et al59 concluded that there is evidence that acupuncture can provide some short-term relief for specific shoulder pathologies (such as adhesive capsulitis), while more evidence is needed for a stronger recommendation regarding its use. On the other hand, Cox et al53 concluded that the evidence for acupuncture in patients with shoulder pathology is inconclusive.Systematic reviews have evaluated acupuncture for treatment of various ailments of the shoulder.64 Gadau et al reviewed 19 RCTs concluding that acupuncture was more effective than sham acupuncture. However, they note that every study included had at least one flaw in terms of bias, and that the longest length of follow-up for any study was 6 months. They are thus cautious in their final conclusion, pointing out the need for further high-quality evidence to make a more informed conclusion.63 Cox et al53 done a sensitivity analysis of several highly flawed trials claiming that acupuncture provided benefit for the treatment of lateral epicondylitis, but concluded that any evidence of benefit was likely due to methodological bias and therefore not useful in making recommendations. Finally, Mansfield et al conducted a systematic review and meta-analysis of 21 studies analyzing muscle force production. The authors found no benefit of acupuncture in muscle strength or pain of the shoulder after acupuncture compared with physical therapy.64 Based on the available literature, no recommendation can therefore be made regarding the use of acupuncture to treat upper extremity pathology.Acupuncture has also been investigated for other upper extremity pathologies, including lateral elbow pain, lateral epicondylitis, and bicep brachii pain.65 showed an increase in knee flexion and extension isokinetic strength in young soccer players after an acupuncture regimen compared with their baseline before acupuncture. Other studies have failed to show a performance benefit of acupuncture, demonstrating no benefit in one-legged vertical jump when compared with placebo.66 For endurance athletes, acupuncture has been shown to be equivalent to both placebo and sham acupuncture in nonathletes in terms of heart rate, rating of perceived effort, oxygen uptake, and ventilation at submaximal effort during a cycling exercise and showed an insignificant time difference in a 20-km cycling test in experienced cyclists when compared with no treatment and sham acupuncture.67 However, these studies only looked at immediate results of acupuncture, and no long-term follow-up was included. There are limited data regarding acupuncture as a performance aid, and the available literature is conflicting regarding whether acupuncture does provide any performance advantage.A new area of research for acupuncture is as an ergogenic aid in sports performance. Several studies have been done on both athletes and nonathletes to assess whether acupuncture can increase performance. Ozerkan et al53In terms of safety, only a minority of studies included reports on adverse events. Reported adverse events included ecchymosis, transient paresthesia, fainting, and dizziness.There is insufficient evidence to definitively conclude that acupuncture is an effective treatment modality for musculoskeletal disorders. Some studies have shown a benefit of acupuncture, particularly in the immediate relief of pain for carpal tunnel syndrome and as an adjunct for the treatment of low back pain. Meanwhile, the data evaluating acupuncture as a tool to treat various pathologies of the shoulder and elbow are inconclusive, as is the data relating to the use of acupuncture as a performance enhancing modality. Given the popularity, safety, relatively low cost, anecdotal evidence, and potential of this nonsurgical modality, acupuncture deserves to be investigated through high-quality, unbiased randomized controlled trials with procedure standardization.


This prospective study aimed at assessing the effects of anxiety and a follow-up text message on pain perception after the installation of fixed orthodontic appliances and its impact on the patients’ routine. t-test, chi-square and Spearman’s correlation tests. All statistical tests were performed with significance level of 5%. The sample of this study consisted of 103 orthodontic patients, 40 males and 63 females (mean age 20.5 years), distributed in two groups: G1 (n=51), including control patients that did not receive any post-procedure communication; and G2 (n=52), including patients that received a structured text message. In baseline phase, the patients completed a questionnaire to assess their level of anxiety prior to treatment. Pain was assessed by using 100-mm visual analog scale (VAS) in baseline and ten times prospectively in predetermined time points. VAS was also applied to assess the patient’s routine alterations caused by the pain. All data were analyzed using ANOVA, Tukey, Mann-Whitney, p< 0.05). Maximum mean pain intensity was detected in the second treatment day (G1=36.9mm and G2=26.2mm) and was significantly higher in G1. Nearly 53% of the patients in G1 reported alterations in the routine (18.8mm), while in G2 the percentage rate reached 28.8% (9.9mm) (p=0.013).  Low-level and high-level anxiety was observed in 42.7% and 7.8% of the patients, respectively. Statistically significant correlation was observed between anxiety and pain (Anxious patients report more pain after the installation of orthodontic appliances. Text messages were effective to reduce pain levels and to decrease the negative effects on patients’ daily routine. Pain is usually experienced in the beginning of the orthodontic treatment.6,7 may also be affected by the increase in pain.6,8 Combined with anxiety, the increased perception of pain may hamper social and daily activities, especially eating and sleeping. Consequently, patients may respond by self-medicating3 and perhaps asking to quit the orthodontic treatment.8-11 This harmful combination could be attributed to specific dental stimuli that may trigger severe levels of anxiety that interfere with the orthodontic treatment.Aside from the physical complaints, psychological aspects, such as cognition, socialization and personality,13,15,16 and text messaging,8,13,17 It has been reported that after dentoalveolar surgery, most patients are satisfied with telephone follow-up, and it was suggested that this type of follow-up procedure should always be done, both in public and private health services,The search for strategies to reduce or eliminate anxiety in patients may contribute to decreasing their perception of pain.Despite the potential association between anxiety and the perception of pain, there is no study dedicated to validate the impact of those variables in the daily routine of patients - especially in the early stage of orthodontic treatment. In practice, the impact of pain perception on patient’s motivation and compliance during the treatment is still unclear. The present study aimed at assessing the association between pain and anxiety in young adult patients after the installation of fixed orthodontic appliances. The hypothesis that text messages could contribute to decrease the pain associated with orthodontic treatment and its impact on patients’ daily routine was also investigated.Centro Universitário Unisagrado (CAAE 53269815.5.0000.5502). All the patients  signed an informed consent form to participate in the study.This prospective study was performed after the approval of the Committee of Ethics in Research of The patients were recruited from private dental offices between January 2016 and April 2017. According to the inclusion criteria the patients should be aged 14-30 years old, have permanent dentition with malocclusion and moderate crowding - justifying orthodontic treatment with fixed appliances -, should have access to a smartphone, and good oral health condition. Additionally, the patients that were included in the study had complete orthodontic charts that consisted of clinical records, dental casts, panoramic and cephalometric radiographs, and intra- and extraoral photographs. The exclusion criteria consisted of previous orthodontic treatment, medical history of chronic diseases and chronic self-medication, especially anxiolytic drugs. Power analysis was performed for sample size calculation with a significance level of 5% and test power of 80%. The standard deviation of 17.64 was adopted following the outcomes of Keith et al.The sample was randomly divided into two groups. A computer-generated randomization list was created using Excel . Group 1  consisted of 51 patients  aged between 14.1 and 30 years (mean age: 21.2 years). Group 2 (G2) consisted of 52 patients  aged between 14.2 and 29.11 years (mean age: 19.9 years). G1 started orthodontic treatment not receiving any post-procedure communication, while G2 received these messages via SMS or WhatsApp Messenger . The communication through messages (only one time) was established right after the fixed orthodontic appliances were installed.The fixed orthodontic appliances were installed in all patients from permanent maxillary right first molar to the left maxillary first molar. The initial orthodontic archwire was 0.012-in or 0.014-in nickel-titanium (NiTi). Archwires for leveling were attached with individual elastomeric rings. Before treatment, a single orthodontist applied the Modified Corah Dental Anxiety Scale (MDAS) to patients and they completed the VAS for pain perception, during the orthodontic appointment. MDAS assessed the level of anxiety reported by the patient during the treatment. Scores below 5 indicated very low level of anxiety; scores between 6 and 10 indicated low level; scores between 11 and 15 indicated moderate level; and scores between 16 and 20 indicated extreme anxiety.0) before the installation of appliances; T1) immediately after the installation; T2) 8 hours after the installation; T3) 24 hours after the installation; and daily up to the 7th day (from T4 to T9). The last assessment was scored in the 14th day (T10). All patients received the VAS form to fill at home at the first orthodontic appointment.Pain was assessed by using 100-mm VAS at baseline and ten times in a follow-up period along predetermined time points: TFor the G2 individuals, text messages were sent once to the patients right after the first appointment, in order to improve their motivation, clarify the treatment approach and ask about their well-being in the early stage of orthodontic treatment.th treatment day, the patients answered a questionnaire that registered their perception of pain and the eventual use of analgesics during the treatment. A new VAS was applied to assess the potential alterations in the daily routine of patients, related to the experienced pain. The text messages were sent by the same researcher, as well as the collection and assessment of all data.In the first clinical appointment after the 14t-test was applied to compare groups and indicate if the treatment affected or not the daily routine of patients. Chi-square test associated the use of analgesics and the alterations in the routine of patients. The outcomes of MDAS and VAS were compared with Spearman’s correlation coefficient. All the statistic tests were performed with Statistica  software package version 13, with significance level set at 5%.The comparison of pain perception among different groups and timings was performed using two-way ANOVA test with repeated values for timing. For multiple comparisons, Tukey test was applied. For the comparison of groups considering MDAS, Mann-Whitney test was used. Independent t-tests showed no statistically significant differences between groups, confirming sample pairing .The subjects included in the present study (n=103) were divided into two groups paired by age and sex. Chi-square and According to MDAS, low-level anxiety was observed in 42.7% of the patients . Extreme anxiety was observed only in 7.8%  of the patients. The same tendency regarding anxiety results was found when the groups were analyzed separately . Mann-Wh0 and T1, respectively). Patients with pain before the installation were replaced in the sample. In G1, the mean pain level observed immediately after the appliance placement was 10.8mm, while in G2 it was 7.2mm (0 to T10). This procedure enabled to evaluate if the text messages sent to Group 2 were efficient in reducing the perception of pain. The G2 reached lower pain level than G1 in all time points, except in the T10. th day . Statistically significant differences between groups were observed within 8 hours after treatment, as well within the 2nd, 3rd and 4th treatment days. To assess the level of pain, the patients were requested to complete the VAS before and after the installation of fixed appliances (Tas 7.2mm . Comparip<0.05), except for T3 in G2 (p>0.05) (In order to investigate if the level of anxiety (MDAS) influences the pain perception (VAS), a correlation was performed among the different time points between groups. In all time points, statistically significant higher scores for pain perception were observed in patients with higher levels of anxiety ((p>0.05) .p=0.034) between groups. Most of the patients under analgesic drugs were found in Group 1   of the patients used analgesics during the study. Chi-square test showed a statistically significant difference  .p=0.013). When this alteration was quantified (VAS), G1 presented a mean value of 18.8 ± 2.2 mm and G2, of 9.9 ±1.5mm, a difference considered statistically significant (p=0.002), as seen in Most patients (52.9%) stated that their routine was affected by the orthodontic treatment. Statistically significant outcomes were observed between groups. Patients in G1 were more affected by the orthodontic treatment in relation to G2  were included in this study. Regarding initial malocclusion, all patients presented discrete or moderate crowding. In these patients, the treatment started with 0.012-in or 0.014-in NiTi archwires .p=0.74). This information is important to confirm the homogeneity of the groups and to reduce the risk of bias from variables that could influence the outcomes. This procedure is justified in other scientific studies that indicated more expressive pain perception in females compared to males.,,Considering the influence of sex on pain perception and also the fact that most of the patients were females (n=63), Groups 1 and 2 were compared regarding sex distribution and presented compatibility (p=0.259) (Table 1). This outcome suggested that both groups had similar anxiety rates before treatment. This aspect is extremely important when comparing both groups regarding pain intensity and patients’ behavior after receiving text messages.On the other hand, pain is not exclusively associated with physical stimuli, but also related to cognitive and emotional aspects. Anxiety is pointed to as the main psychological aspect related to the perception of pain.According to the present study, patients with higher anxiety level are more prone to complain of intense pain . The samnd treatment day , while less pain was referred in the 14th treatment day . Statistically significant differences were observed between groups within 8 hours after the installation of the orthodontic appliances, as well within 2, 3 and 4 days. Accordingly, Bartlett et al,,Considering anxiety as a contributing factor to pain experience,24 Hence, any approach, such as text-messaging, to decrease the use of medication may benefit patients. These findings corroborate the studies of Cozzani et alAccording to p=0.002) were also observed between groups. G1 presented a mean value of 18.8±2.2mm and G2, of 9.9±1.5mm  patients complained about routine alterations due to the pain experienced during the initial phase of treatment. The comparison between groups revealed statistically significant differences. In particular, patients in G1 had their routine more affected (52.9%) by the pain than the patients in G2 (28.8%), as seen in .9±1.5mm . In thisThe present study provided relevant data regarding pain perception and the level of anxiety in orthodontic patients after the installation of fixed appliances. As a limitation of the study, the patients were evaluated only 14 days after the installation of orthodontic appliances. In future research, we may consider sending text messages or phone calls follow-up for a longer period of evaluation. Based on the findings, the present study suggests the use of text messages to explain and clarify the treatment progress in order to minimize the perception of pain in the early phase of orthodontic treatment.» Anxious patients presented higher pain levels during initial phase of orthodontic treatment.nd, 3rd and 4th treatment days when they received the post-procedure message.» When the perception of pain was compared between groups, significantly reduced pain was perceived by patients within 8 hours after appliance installation, as well within the 2» A significant difference in routine alteration was observed between groups, patients that were not contacted with text message had their routine affected twice as much due to the pain experienced.


The atypical DM group had the highest risks of POCE (hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.48–2.10), all-cause death  and any MI  in the adjusted model. In conclusion, atypical chest pain was significantly associated with mortality in patients with AMI. Among four groups, the atypical DM group showed the worst clinical outcomes at 2 years. Application of rapid rule in/out AMI protocols would be beneficial to improve clinical outcomes.Atypical chest pain and diabetic autonomic neuropathy attract less clinical attention, leading to underdiagnosis and delayed treatment. To evaluate the long-term clinical impact of atypical chest pain and diabetes mellitus (DM), we categorized 11,159 patients with acute myocardial infarction (AMI) from the Korea AMI-National Institutes of Health between November 2011 and December 2015 into four groups . The primary endpoint was defined as patient-oriented composite endpoint (POCE) at 2 years including all-cause death, any myocardial infarction (MI), and any revascularization. Patients with atypical chest pain showed higher 2-year mortality than those with typical chest pain in both DM (29.5% vs. 11.4%,  Chest pain is one of the cardinal symptoms that warrants a visit to the emergency department (ED) . Among pDiabetes mellitus (DM) is considered to have a risk equivalent to that of coronary heart disease, and global prevalence is gradually increasing ,9. DiabeThe Korea Acute Myocardial Infarction-National Institutes of Health registry (KAMIR-NIH) is a prospective, multicenter, nationwide observational cohort study (cris.nih.go.kr identifier: KCT-0000863). Patients diagnosed with AMI in 20 tertiary hospitals from November 2011 to December 2015 were enrolled in the study. The details of this study have been published previously . This st2. The features of chest pain were classified as typical or atypical chest pain according to the guidelines for the management of patients with non-ST-elevation acute coronary syndromes [Diagnosis of AMI was based on the presenting symptoms, serial ECG changes suggesting myocardial infarction (MI), and an increase in cardiac biomarkers, especially cardiac troponins above the 99th percentile of the upper reference limit. ST-segment elevation myocardial infarction (STEMI) was defined as new ST-segment elevation in more than two contiguous leads, measuring > 0.2 mV in leads V 1–3 or 0.1 mV in other leads, or a new left bundle branch block on 12-lead ECG with at least one positive cardiac troponin T or I. Non-STEMI (NSTEMI) was defined as at least one positive cardiac biomarker without ST-segment elevation. Chronic kidney disease (CKD) was defined as eGFR < 60 mL/min/1.73 myndromes .Data were recorded using a Web-based case report form in the Clinical Data Management System (iCReaT) of the Korea NIH by the physicians and trained coordinators. Demographic and baseline characteristics, including cardiovascular risk factors, other comorbidities, initial presenting symptoms, time of presentation, hospital arrival time, balloon time, and laboratory findings were collected. Angiographic findings and details of procedural characteristics, echocardiographic results, and medications were recorded. Treatment strategy and prescription of medications were based on the physician’s discretion. Patients were treated with the standard of care according to the guidelines. Patients were followed up through out-patient clinic visits or by telephonic interviews. Death, MI, and repeat revascularization were assessed at discharge and during the clinical follow-up period.The primary endpoint was defined as patient-oriented composite endpoint (POCE) at 2 years including all-cause death, any MI, and any revascularization. The secondary endpoint was a device-oriented composite endpoint (DOCE) at 2 years including cardiac death, target vessel MI, and target lesion revascularization (TLR). Other secondary endpoints included individual components of POCE and DOCE. Death was considered as cardiac death if the apparent non-cardiac cause of death did not exist. Target vessel MI was defined as the presence of ischemic symptoms or ECG changes with an elevation of cardiac biomarker above the upper limit of normal related to a previously treated target vessel. TLR was defined as repeated revascularization of the target lesion.t-test. Categorical variables are expressed as frequencies (percentage) and compared with the chi-square test or Fisher’s exact test. Two-year Kaplan-Meier survival curves of four groups were compared using the log-rank test. The hazard ratios of study outcomes were evaluated using Cox proportional hazards models in the unadjusted and adjusted models. Multivariable-adjust proportional hazard model included age, sex, body mass index, hypertension, chronic kidney disease, dyslipidemia, current smoker, clinical diagnosis, systolic blood pressure, heart rate, Killip class ≥ 2, symptom to door time, and door to balloon time. Potential effect modification by sex, age (≥75 years), diabetes, CKD, clinical diagnosis, multivessel disease, and left ventricular ejection fraction (≥40%) was evaluated through the stratified analysis and interaction testing using a likelihood ratio test. Statistical analyses were performed using SAS 9.4 version . Statistical significance was considered when p < 0.05.Continuous variables are expressed as mean ± SD or median (interquartile range) and assessed using the Wilcoxon signed-rank test or two-sample Among 11,161 patients, 1386 (12.4%) patients had atypical chest pain and 3103 (27.8%) had DM. More patients with atypical chest pain were females and older in both DM and non-DM groups . Those wPatients with atypical chest pain showed more prevalence of multivessel disease in both DM and non-DM groups . No diffp < 0.0001; 7.8% vs. 2.3%, p < 0.0001, respectively). The incidences of POCE and all-cause death at 2-year were 17.2% and 9.7%, respectively. The 2-year rate of POCE and DOCE were about twice higher among patients with atypical pain than among those with typical chest pain. All-cause death and cardiac death rate were the main contributing factors of the difference. The 2-year cumulative incidence of all-cause death was highest in the atypical DM group (29.5%) among the four groups. In the logistic regression analysis, patients in the atypical DM group were at the highest risk of POCE (hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.48–2.10), all-cause death , and any MI  in adjusted models (p for trend < 0.0001) among the four groups. The cumulative incidences of primary and secondary clinical endpoints were significantly different (log-rank p < 0.0001) .Median follow-up duration was 730 days (interquartile range 687–759 days). Overall in-hospital death occurred in 388 (3.5%) patients . In-hospd models , as well 0.0001) . Atypica 0.0001) . PatientPatients with atypical chest pain were older, affected more females, had more comorbidities, delayed admission, and delayed treatment.Patients with atypical chest pain showed higher in-hospital death and long-term mortality irrespective of diabetes history.The coexistence of atypical chest pain and DM was at the highest risk of cardiovascular events.The main purpose of this study was to evaluate the long-term clinical impact of atypical chest pain among patients with AMI. The key findings were as follows:To differentiate typical chest pain from atypical or noncardiac origin is challenging, because the value of chest pain characteristics is limited. Although typical features of chest pain are well described ,13, a prSeveral studies reported the in-hospital mortality for patients with atypical chest pain in the ACS setting. In the National Registry of Myocardial Infarction 2 (NRMI-2) including 1674 hospitals in the United States from June 1994 to March 1998, 142,445 (33%) of 434,877 patients diagnosed with MI complained of no chest pain on presentation. The rate of in-hospital mortality was 23.3% among patients without chest pain compared with 9.3% among those with chest pain , the in-n = 660) and incomplete data (n = 366) among 2672 patients. Although our study has a relatively shorter follow-up period than did the SWEDEHEART registry and MONICA/KORA MI registry, the strength of this study is that all the patients were treated with percutaneous coronary intervention, and most clinical events were clearly identified. In addition, hard endpoints, such as death and MI were monitored and captured by the government insurance system.There is a lack of evidence on whether atypical chest pain affects long-term clinical outcomes. SWEDEHEART registry included 172,981 AMI patients between 1996 and 2010 . One of In this study, the combination of atypical chest pain and diabetes history showed the highest incidence of cardiovascular events. These worst outcomes can be explained by the adverse effect of diabetes itself and diabetic autonomic neuropathy. Approximately one-third of type 2 diabetic patients are known to experience serious cardiovascular complications, such as coronary heart disease, MI, and stroke ,20. FurtModifiable cardiovascular risk factors are substantial targets to reduce mortality. Data from the National Health and Nutrition Examination Survey and Behavioral Risk Factor Surveillance System in the U.S. demonstrated that one third to half of diabetic patients did not reach the target goal of blood sugar level, optimal blood pressure, or low-density lipoprotein (LDL)-cholesterol level . IntensiFourth universal definition of MI emphasizes that the use of high-sensitivity cardiac troponin assays is beneficial to rule in/out myocardial injury and to define MI with specific subtypes . AlthougThis study has several limitations. First, this is a prospective, observational multicenter registry, not a randomized controlled design. However, it is difficult to randomize therapeutic strategy according to the presenting symptom because there may be an ethical problem to delay interventional treatment. Second, only 20 tertiary hospitals participated in this registry, and this would not represent the overall population in our country. Third, the duration of diabetes and detailed medications were not analyzed in this study. Fourth, propensity score-matched analysis was not considered because most of the baseline characteristics were heterogeneous between the typical and atypical chest pain groups.Atypical chest pain was significantly associated with mortality among patients with AMI. Among four groups, atypical DM group showed the worst 2-year clinical outcomes regarding POCE, all-cause death, and any MI at 2 years. Application of rapid rule in/out AMI protocols would be beneficial to improve clinical outcomes in patients with atypical chest pain.