Latent profile analysis (LPA) was performed to identify the number of homogeneous classes present and to further define the pain classification system. The EFA combined the 11 PROMIS domains into four unidimensional superdomains of biopsychosocial dysfunction: Pain, Negative Affect, Fatigue, and Social Function. Based on multiple fit criteria, a latent class model revealed four distinct classes of CPP: No dysfunction (3.2%); Low Dysfunction (17.8%); Moderate Dysfunction (53.2%); and High Dysfunction (25.8%). This study is the first description of a novel approach to the complex disease process such as chronic pelvic pain and was validated by demographic, medical, and psychosocial variables. In addition to an essentially normal class, three classes of increasing biopsychosocial dysfunction were identified. The LCA approach has the potential for application to other complex multifactorial disease processes.Chronic pelvic pain affects multiple aspects of a patient's physical, social, and emotional functioning. Latent class analysis (LCA) of Patient Reported Outcome Measures Information System (PROMIS) domains has the potential to improve clinical insight into these patients' pain. Based on the 11 PROMIS domains applied to  These pis.org/) . The coris.org/) .Given the power of the PROMIS and the 11 domain scores, quantifying CPP into stages of pain appears to be a logical next step in understanding CPP. The benefits of a pain classification system are well known in oncology: planning treatment, estimating prognosis, identifying clinical trial suitability, and providing a nomenclature for comparisons between patients of similar severity . A cliniThe objective of this study was to develop a classification system for CPP based on the core PROMIS measures. In his seminal 1972 paper “More Is Different,” Nobel laureate Andersen posits that systems of increasing complexity cannot be evaluated based on standard reductionist approaches. Instead, “fascinating… and basically new” methods are required to gain a firm understanding of the behavior of these complex systems [http://www.assessmentcenter.net/) to 613 patients referred for evaluation in the Chronic Pelvic Pain Center [A Summa Health System Institutional Review Board approved protocol permitted measurement of the health status across multiple domains. This was administered via the online PROMIS Assessment Center , education level, and insurance status. Medical variables studied included smoking status, gravidity (number of pregnancies), parity (number of live births), months of pain (6 quantiles), number of pain-related surgeries, and number of pain-related physicians seen. We employed an abbreviated form of the Childhood Trauma Questionnaire Short Form (CTQ) composed of six items designed to measure sexual, physical, and emotional abuse and physical and emotional neglect . The PosThe analysis sought to identify homogeneous classes of patients across multiple domains of self-reported biopsychosocial health. Patient classification was done by conducting a latent profile analysis (LPA), a type of latent class analysis in which the class indicators are continuous variables like the standardized PROMIS scores . LPA modFirst, to minimize within-class variability, an exploratory factor analysis was conducted to identify and combine PROMIS scores that are strongly correlated, as it is known that many of the 11 PROMIS scores are highly correlated with one another. The EFA (results not shown) produced four unidimensional superdomain scores: pain , negative affect , fatigue , and social function  . Third, To identify the optimal number of latent classes present, LPA evaluated between one and six potential latent classes based on the four superdomains' average scores. A hypothesis based on pelvic pain scores published previously  proposedAfter selecting the optimal number of latent classes, CPP patients were staged into their highest probability class. Post hoc descriptive statistics were calculated to produce a demographic, medical, and psychosocial profile for each class. Both EFA and LPA were conducted with Mplus version 7.18  and postDetermination of the number of latent classes is shown in Post hoc demographic characterizations of patients within each of the latent classes are shown in Note that statistical comparisons are not made for post hoc demographic, medical, or psychosocial characteristics across classes. Class membership of patients is assigned based on highest probability, but as standard statistical procedures such as ANOVA assume class membership is known with certainty, such tests will have high type I error rates and therefore are not appropriate.This is the first application of latent class analysis of patient reported PROMIS measures to evaluate patients with CPP. Using 11 domains from the PROMIS CAT methodology, EFA produced four unidimensional superdomains of biopsychosocial function . Two of these  provided an excellent separation of the four classes identified. These findings indicate that patients using the PROMIS approach segregated into four biopsychosocial function groups: Class 3: high dysfunction; Class 2: moderate dysfunction; Class 1: low dysfunction; and Class 0: no dysfunction. The majority of patients (96.2%) had some significant level of pain. Very few (3.8%) reported no pain, and these Class 0 patients are likely similar to healthy, normal women even though they were referred for pelvic pain evaluation .Using the PROMIS for evaluation not only follows current trends in medicine, but until a widely available, noninvasive, and cost effective neuroimaging protocol for pain matrix pathology identification is available, such a system provides a patient-centered approach to comprehensively evaluate a subjective process using an objective system . One of Due to the complexity of the pain experience and difficulty in predicting outcomes for individual patients, latent class modeling provides a very useful approach to chronic pain evaluation. These would include maladaptive brain-derived neurotrophic factor activity , centralClinical phenotyping to predict treatment response is one potential use of LCA. Applying a latent class approach to multidimensional, biopsychosocial QOL and other measures in opiate-dependent patients in Belgium similarly produced a three-class model, with all dimensions clustering together into subjects with low, medium, and high levels of functionality . In cancThe characteristics of this patient population and how it segregates into stages  provide This particular study demonstrates a number of strengths. Although a priori sample size for latent class analysis can be difficult to determine, a general rule of thumb is that, for every statistical parameter estimated , at least 20 cases must be present. For this study, our sample of 613 CPP patients and the creation of the four superdomains of biopsychosocial function permitted us to evaluate LPA models with up to six classes . An additional study strength is that it is based on a referral population that has previously been shown to be reflective of chronic pelvic pain patients seen in a general gynecology practice [The use of biopsychosocial function outcome measure based latent class modeling can have a range of limitations. On an allocation level, the mathematical algorithm provides only probability values for any one patient to be in any of the potential classes; thus categorical assignment must possess a nonzero level of ambiguity. The actual analysis is dependent on the population from which it is drawn, and although previously cited studies indicate that there can be substantial stability of latent classes across international regions, this result is not guaranteed without further testing in a broader population of CPP patients. Belonging to a particular class may not provide immediately useful clinical information, and further research is required to understand the significance and utility of class membership. One immediate benefit of using the current PROMIS-based system is that it is free to use through assessment center, and patients classified into the high biopsychosocial dysfunction class may be best managed in a multidisciplinary setting where psychiatry, physical therapy, sleep studies, social work, and pain management can be included in patient care.These results address the hypothetical question: “Are there measureable classes in patients with CPP?” As a measurement model, the PROMIS is designed only to group patients according to their PROMIS biopsychosocial measure scores. Future work on a predictive model would test the hypothesis that latent class membership can be predicted based on other pertinent neuropsychological tests or physical examination. Although not formally modeled here, the results shown at the end of The results of this study indicate that patients with chronic pelvic pain can be categorized based on a multidimensional biopsychosocial quality of life scale. This takes into account not just pain and its impact, but also psychological distress, social functioning, and sleep quality. Clinically, these results demonstrate that the PROMIS CAT system is easy to deploy in clinical practice. Patients classified into Class 3, high biopsychosocial dysfunction, are substantially different from patients in the other three classes. This suggests that Class 3 patients are appropriate for more intensive resource utilization such as psychological, physical therapy, or tertiary referral. The research implications are quite broad, including insuring that these classifications are valid at other pain centers, discovering the underling neurophysiology, and developing practical protocols to assist with the clinical management of these complex patients.Latent class analysis of patient reported outcome measures demonstrated four classes of biopsychosocial dysfunction , validated by pain history and stress.


Laparoscopic surgery is fast becoming the treatment of choice for inguinal hernia. By reviewing our 10-year experience of performing totally extraperitoneal repair (TEP), we sought to establish its clinical significance in the treatment of adult inguinal hernia.We reviewed retrospectively the clinical records of patients who underwent TEP for adult inguinal hernia between January 2003 and December 2012.n = 32) vs indirect (n = 128) hernias in the primary unilateral inguinal hernia group  and between direct/direct (n = 31) vs indirect/indirect (n = 24) hernias  in the primary bilateral inguinal hernia group. The only postoperative complications recorded were four cases of hernia recurrence (1.3 %) and one case of chronic pain (0.3 %).None of the 303 patients with adult primary or recurrent inguinal hernia in our study needed TEP converted to other procedures or suffered serious complications during the procedure. A significant difference was noted in the operation time between direct (The results obtained for TEP over 10 years support this as a promising procedure for the treatment of adult inguinal hernia. Laparoscopic surgery has become increasingly popular because patients want surgery that is minimally invasive. Hence, it has been gradually gaining acceptance as the treatment of choice for inguinal hernia. The main advantage of laparoscopic surgery for the treatment of adult inguinal hernia lies in the reduction of both the size of the wound and postoperative pain, thereby improving postoperative recovery as well as cosmesis –3. MoreoA recent randomized controlled trial comparing TEP with the Lichtenstein procedure demonstrated promising postoperative outcomes such as decreased postoperative pain and shorter recovery time for TEP , but prat test on SPSS ver. 8.01 . The nominal data from two independent groups were compared by the Chi-square test or Fisher’s exact probability test. Values are expressed as mean ± standard deviation (SD). A p value of less than 0.05 was considered significant.The diagnosis of inguinal hernia was made based on a physical examination and computed tomography (CT) scans done with the patient in the prone position at the outpatient clinic. TEP was indicated in both primary and recurrent inguinal hernias, which were reducible in the supine position. TEP was contraindicated in cases of incarceration or after dissection of the preperitoneal space. All patients provided written informed consent before surgery. The clinical records of patients who underwent TEP for adult inguinal hernia between January, 2003 and December, 2012 were reviewed retrospectively. Clinical outcomes included the operation time, intra- and postoperative complications, length of postoperative hospital stay, hernia recurrence, and chronic pain (defined as pain that persisted for more than 2 months). Postoperative complications were graded according to the Clavien–Dindo Classification . PatientA balloon-equipped trocar  was inserted into the preperitoneal space through a small infraumbilical incision and the balloon was inflated for 2 min to allow blunt dissection of the preperitoneal space. After deflating the balloon, pneumoperitoneum was created and maintained at 8 mmHg. Additional 2 ports were inserted in the midline of the lower abdomen, following which the preperitoneal space was dissected and the hernia sac was explored laparoscopically. In indirect inguinal hernia, the hernia sac was dissected from the spermatic sheath and divided after the ligation, whereas in direct inguinal hernia, the hernia sac was reduced immediately after the balloon dissection. The myopectineal orifice was repaired with inlay mesh that was secured with absorbable tacks .TEP was performed for adult inguinal hernia in 303 patients Table . The prin = 175) and 111 ± 44 min in the bilateral group (n = 86). There was a significant difference in the operation time for primary unilateral inguinal hernias between the direct (n = 32) and indirect (n = 128) groups . A similar trend was seen in the operation time for primary bilateral inguinal hernias between the direct/direct (n = 31) and indirect/indirect (n = 24) groups . There was no case of conversion to other procedures or serious complications during the operation. The peritoneal injury (n = 51) was repaired with an intracorporeal suture and the resulting pneumoperitoneum was deflated by the puncture with the needle placed into the peritoneal cavity during the operation. The postoperative hospital stay was 5 ± 4 days. Postoperative complications comprised four cases of hernia recurrence (1.3 %) and one case of chronic pain (0.3 %). All four cases of seroma and eight cases of subcutaneous hematoma, resolved with conservative treatment (Grade I in Clavien–Dindo Classification). In 24 patients with recurrent inguinal hernia after conventional non-mesh repair (n = 13), mesh-plug repair (n = 8), preperitoneal mesh repair (n = 3), TEP was completed without any serious intraoperative complications although postoperative subcutaneous hematoma (GradeI in Clavien–Dindo Classification) developed in two of these patients  and hematoma, seroma, and recurrence in the postoperative course (data not shown). One patient (0.3 %) suffered refractory inguinal pain that persisted for more than 2 months after TEP, and this was treated successfully with medication. Our data support the hypothesis that laparoscopic surgery results in a decreased incidence of postoperative chronic pain because of the reduced size of the wound, although it is known that various operative factors, including the choice of mesh (heavy vs light weight) and tacker , also affect the duration of postoperative inguinal pain or discomfort –17. AccoIn conclusion, a review of our 10-year experience of performing TEP demonstrated a lower incidence of intra- and postoperative complications, including hernia recurrence and chronic pain. These findings support TEP as a promising treatment for adult inguinal hernia repair.


Effective control of postoperative pain remains one of the most important and pressing issues in the field of surgery and has a significant impact on our health care system. In too many patients, pain is treated inadequately, causing them needless suffering and they can develop complications as an indirect consequence of pain. Analgesic modalities, if properly applied, can prevent or at least minimize this needless suffering and these complications.The aim of this study was to compare the efficacy of continuous infusions of local anesthetic drugs by paravertebral and epidural routes in controlling postoperative pain in patients undergoing hip surgeries.The study involved 60 patients who were undergoing hip surgery under the subarachnoid block. They were randomly divided into 2 groups of 30 patients. Group I  received a single dose of spinal anesthesia with 2.5 mL 0.5% bupivacaine (heavy) + a continuous infusion of 0.125% bupivacaine at 5 mL/h in the paravertebral space. Group II  received a single dose of spinal anesthesia with 0.5% bupivacaine (heavy) + a continuous infusion of 0.125% bupivacaine at a rate of 5 mL/hr in the epidural space for 48 hours in the postoperative period. Visual analogue scale (VAS) score, vital statistics, rescue analgesia, and procedure time were compared with the corresponding times between the 2 groups by student’s t-test and repeated measures ANOVA with post hoc Bonferroni. P < 0.05 was considered significant. There were no statistically significant differences between the 2 groups regarding mean pain score in the first 48 hours.Mean arterial pressure was significantly lower in the epidural group compared with the paravertebral group from 2 hours after start of the infusion until 48 hrs. Regional anesthesia procedure time was significantly longer in the epidural group (P < 0.001). There was no significant difference between the 2 groups regarding frequency of postoperative complications and catheter-related problems.The results of our study indicate that for patients who are scheduled for hip surgery, both continuous paravertebral and continuous epidural analgesia are effective in controlling postoperative pain but that the former has several crucial advantages. The conquest of pain that is inherent to surgery is the most important event in the history of mankind. Pain following surgery is a universal phenomenon; yet, it is often underestimated and undertreated. This is likely due to difficulties in balancing an effective postoperative pain treatment regimen with acceptable side effects.Effective control of postoperative pain remains one of the most important and pressing issues in the field of surgery and has a significant impact on our health care system. Most of the hundreds of millions of people worldwide who undergo operations each year experience pain of varying intensity. In too many patients, pain is treated inadequately, causing them needless suffering, and they can develop complications as an indirect consequence of pain. Analgesic modalities, if properly applied, can prevent or at least minimize this needless suffering and these complications.Pain following hip surgery, which constitutes the majority of operations , especiaAdequate postoperative pain relief improves the surgical outcome in terms of reduced morbidity, reduced hospital stay in the postoperative period , and redSome of these techniques are also associated with unpredictable responses and complications. When compared with other techniques, many regional analgesic techniques, such as epidural and paravertebral blocks, provide superior pain relief, may favorably influence outcomes with regard to blood loss and thromboembolic events , and canThe purpose of this study was to compare the efficacy of postoperative pain relief after hip surgery using lumbar epidural and lumbar paravertebral anesthetic (Psoas compartment block) with a continuous infusion of 0.125% bupivacaine.A randomized, controlled comparative study of 60 patients who were scheduled for hip surgery was performed. After the ethical committee approved the study design, we enrolled American society of anesthesiologist (ASA) class I, II, and III patients who were scheduled for unilateral hip surgery. Written informed consent was obtained.Patients with the following criteria were excluded from the study:Lack of patient consentSepsis over lumbar vertebraPatient on chronic analgesic/anticoagulant therapyPatient with a neurological disorderKnown allergy to any local anestheticDementia that prevented proper comprehensionSixty such patients formed the total sample size and were randomly allocated into groups of 30 subjects.Group I: 5 mL/h, 0.125% bupivacaine, continuous paravertebral groupGroup II: 5 mL /h, 0.125% bupivacaine, continuous epidural groupInformed written consent was obtained from each patient after the study protocol and use of the visual analog scale were explained and after we gained their confidence during the preanesthetic assessment visit on the night before surgery.During the preanesthetic assessment, a detailed history of each patient was taken and recorded in Performa. A thorough clinical examination was performed. Detected to be having any of the conditions mentioned in exclusion criteria were excluded from the study. Hematological measures, such as hemoglobin, blood count, bleeding time, and clotting time, were recorded, and routine and microscopic urine analysis was performed. Chest X-ray and electrocardiogram (ECG) were taken whenever necessary. All patients were visited the night before the surgery and had the procedure explained to them; after being advised and reassured, their confidence was gained. All patients were advised to fast after 2200 hours the night before the surgery.All patients were given tablet alprazolam 0.25 mg orally at 10 pm in the night before surgery.Patients pulse rate, ECG, and noninvasive blood pressure were recorded, and a wide-bore intravenous line was established. Patients were preloaded with Ringer’s solution at 15 mL/kg body weight 30-60 minutes before intrathecal drug administration. Patients were positioned in the sitting position, supported, and chin-flexed on the chest; those who were unable to sit were positioned in the lateral decubitus position. The back was prepared using Ioprep and wiped with methylated spirit, and the area was draped with a sterile towel.To locate the puncture site, a point was made on the upper border of the spinous process of the L2 vertebra, and we identified the punctured site 3 cm lateral to the first point on the target side. Local anesthetic was infiltrated at the puncture site, and a 16-G Tuohy needle was advanced perpendicular to all planes until it made contact with the transverse process of the L2 vertebra.It was then redirected slightly caudal to the transverse process and advanced 1-2 cm to reach the Psoas compartment. The stylet was removed, and 10 mL of saline was injected to expand the compartment. Next, an 18-G catheter was inserted through the Tuohy needle and advanced approximately 4 cm caudally within the compartment. Initially, a 3-mL test dose solution containing 2% lidocaine and 1:200,00 epinephrine was injected via the paravertebral catheter.Then, a lumbar puncture was performed through the L3-L4 interspace, and 2.5 to 3.0 mL of 0.5% bupivacaine was injected.The L3-L4 interspace was identified and infiltrated with local anesthetic. A 16-G Tuohy needle was inserted through the the L3-L4 interspace, and the epidural space was located by loss of resistance technique. The stylet was removed, and a 3-mL test dose solution containing 2% lidocaine and 1:200,00 epinephrine was injected. Then, a lumbar puncture was performed with a 25-G spinal needle, which was passed through the Tuohy needle, and 2.5-3.0 mL of 0.5% bupivacaine was injected. The catheter was then advanced approximately 2-3 cm cephalad and secured.The cephalad spread of analgesia and the degree of motor blockade of the lower limb were recorded. The level of sensory blockade was assessed using a 25-gauze short-bevel needle and recorded as analgesia to loss of sensation to a pin prick . The folHeart rate and ECGNoninvasive blood pressureSPO2 (pulse oximetry)Blood lossUrine outputIV fluid inputPatients were observed for any discomfort, nausea, vomiting, shivering, pain, bradycardia, and any other side effects, and the need for any additional medications was recorded. IV fluids were administered in the form of Ringer’s lactate, dextrose normal saline, and colloids in calculated doses, depending on the weight of the patient, and further adjusted as per blood loss during surgery. Hypotension of more than 30% of the preanesthetic value was treated with rapid infusion of fluids and an injection of mephenterine intravenously. Bradycardia (heart rate less than 60/mt) was treated with intravenous atropine sulphate.At the end of the operation, each patient was connected to an infuser set to deliver an infusion of 0.125% bupivacaine at a rate of 5 mL per hour for 48 hours. All patients were observed in the postanesthesia care unit and then in the ward. Immediately after surgery, each patient started identical physical therapy regimens. From postoperative Day 1, patients performed active and assisted hip flexion and extension exercises against gravity twice daily. Getting up from bed was encouraged as soon as possible, followed by ambulation with a walker. Several parameters were assessed postoperatively.Regional anesthesia procedure time; i.e., the period from positioning the patient for technique to catheter fixation.Operation timeSeverity of pain using the 10-cm visual analog scale and vital parameters, such as pulse, mean arterial pressure (MAP), and respiratory rate (RR) at 2, 4, 8, 12, 18, 24, 32, 40, and 48 hoursSupplemental analgesic requirementCatheter-related problems and any complications in first 48 postoperative hoursRescue analgesia was provided by Inj. diclofenac 1 mg/kg IMA total of 60 patients were studied. They were randomly divided into 2 groups of 30 patients each. Six patients were excluded from the study. The data that we present are from the remaining 54 patients . Group I - 28 patientsGroup II - 26 patients 5The hemodynamic parameters that we measured were heart rate and mean arterial pressure. The preoperative heart rate (HR) and MAP of all patients were recorded before the procedure was performed. Subsequent readings were taken every 5 minutes. Intraoperatively after spinal anesthesia and thereafter recorded at 2, 4, 8, 12, 18, 24, 32, 40 and 48 hours.The results of our study indicate that for patients who are scheduled for hip surgery, both continuous paravertebral and continuous epidural analgesia are effective in controlling postoperative pain but that the former has several crucial advantages. We modified the posterior approach technique of Deckrey et al., Chayen et al. , and WinLocal anesthetic was infiltrated at the puncture site, and a 16-G Tuohy needle was advanced perpendicular to all planes until it made contact with the transverse process of the L2 vertebra. It was then redirected slightly caudal to the transverse process and advanced 1-2 cm to reach the Psoas compartment. The stylet was removed, and 10 mL saline was injected to expand the compartment. Next, the 18-G catheter was inserted through the Tuohy needle and advanced approximately 4 cm caudally within the compartment to reach the vicinity of the L4 vertebra, based on the finding that most branches of the lumbar plexus are in close proximity in the region of the 4th lumbar vertebra in the Psoas compartment. The efficacy of this postoperative pain management was assessed using the VAS.Six patients were excluded from the study. In 2 patients, the epidural catheter could not be sited; both patients were aged above 70 years and had mild scoliosis. Three patients-2 in the paravertebral group and 1 in the epidural group—were excluded due to accidental removal of the catheter while transferring them to the ward. One patient from the epidural group withdrew due to persistent hypotension.Vascular puncture was encountered during the procedure in 2 patients; the needle was redirected cephalad to the transverse process, and the block was administered. The data are from the remaining 54 patients.There was no significant difference in mean age, sex, height, weight, or ASA class distribution between patients in this study. The various surgeries that were performed and the duration of surgery were comparable between them. We measured the VAS at 2, 4, 8, 12, 18, 24, 32, 40, and 48 postoperatively. We found that both routes were effective in controlling postoperative pain and did not differ significantly, reflecting good postoperative pain control in both groups. The results of our study are consistent with those of of P.J. Mathews , who didPerttunen et al.  demonstrThe paravertebral block effects a predominantly unilateral sympathetic blockade, whereas an epidural block is usually bilateral; the extent of the spread of the drugs is also greater. These differences might explain the disparities in the incidence of hypotension between the 2 groups. This conquer with the study G Turker et al. , White aIn our study, both continuous paravertebral and epidural analgesia provides effective postoperative pain relief after hip surgery, but the paravertebral block is technically simple and easy to learn with few contraindications, provides hemodynamic stability, and has a low complication rate and is therefore a safe and effective technique in controlling postoperative pain after unilateral hip surgery.


The aim of this study is to investigate how the Charlson Comorbidity Index (CCI) scores contribute to increased length of stay (LOS) and healthcare costs in hip fracture patients.Through retrospective analysis at an Urban level I trauma center, charts for all patients over the age of 60 years who presented with low-energy hip fracture were evaluated. 615 patients who underwent operative fixation of hip fracture or hemiarthroplasty secondary to hip fracture were identified using Current Procedural Terminology (CPT) codes search and included in the study. Data was collected on patient demographics, medical comorbidities, and hospitalization length; from this, the CCI score and the cost to the institution  were calculated.p = 0.014]. Patients with a CCI score of 2 (compared to a baseline CCI score of 0), on average, stayed 1.92 extra days in the hospital, and incurred $8,697.60 extra costs.Multivariate linear regression analysis modeled the length of stay as a function of CCI score. Each unit increase in the CCI score corresponded to an increase in length of hospital stay and hospital costs incurred [effect size = 0.21; (0.0434–0.381); The CCI score is associated with length of stay and hospital costs incurred following treatment for hip fracture. The CCI score may be a useful tool for risk assessment in bundled payment plans.Level III. Hip fracture procedure volumes have risen in recent years, largely due to an aging population, and this trend is expected to increase dramatically in the coming decades, from 250,000 procedures annually to 500,000 by 2040 . With cuA number of scoring systems which summarize the patient’s overall health status have been developed, including the American Society of Anesthesiologist’s score (the ASA score), the Elixhauser score, and the Charlson Comorbidity Index (CCI). Higher ASA scores have been shown to be associated with increased hospital costs secondary to increased LOS in hip fracture patients . SimilarInstitutional review board approval was obtained for this study. This was a retrospective cohort study that included all patients who underwent operative fixation of hip fracture or hemiarthroplasty secondary to hip fracture, including both femoral neck fractures and intertrochanteric fractures, at Vanderbilt University Medical Center, a level one trauma center, from January 2000 to December 2009. Current Procedural Terminology (CPT) codes were used to find patients who had experienced a hip fracture from a low-energy fall and received an intervention of cephalomeduallary nailing (CMN), closed reduction and percutaneous pinning (CRPP), total hip arthroplasty (THR), hemiarthroplasty (hemi), or open reduction internal fixation (ORIF). All patients over the age of 60 years with acetabular, proximal femoral, femoral neck, and trochanteric fractures were selected. Patients with incomplete medical records were excluded. Additional demographic and clinical covariates were collected from our institution’s electronic medical records database. Medical comorbidities were documented preoperatively by routine preoperative assessment, and, from this data, the Charlson Comorbidity Index was calculated according to Deyo’s description .The average total cost to the hospital of an inpatient day  was obtained from the institution’s financial services and the average cost was treated as a unit cost per inpatient day. All fractional LOS values were rounded to the nearest whole number and multiplied by the per day cost.p = 0.05.The primary outcome of interest was the relationship between the CCI and the length of hospitalization. Risk of the occurrence of the outcome of interest (i.e. LOS) was modeled as a function of the preoperative CCI using multivariable linear regression. The multivariate linear regression model controlled for confounders  previously found to be associated with the outcome (i.e. prolonged LOS). Statistical significance was set at Six hundred and fifteen complete records were obtained for isolated low-energy hip fractures in patients 60 years or older who were treated at our Level 1 trauma center. The average age of the hip fracture patient was 78.4 years and 51.7 % of our patients were aged 75–89 years. Caucasians comprised the majority of our patient cohort (84.7 %), followed by African-Americans (7.3 %). Nearly three-quarters of our patient cohort had a CCI score less than 3, and more than half of the cohort had a CCI score of either 0 or 1. Patient characteristics and demographic data are summarized in Table The different surgical procedures performed, classified by CPT codes, and the average LOS and hospital costs incurred for the inpatient stay are summarized in Table p = 0.003); the financial implication of this finding is that each male patient costs the hospital an additional $5,073.60 as compared to a female patient  was also significantly associated with an additional 1.12 (95 % CI 0.375–1.865) days in hospital ; We found that increasing CCI scores are associated with longer LOS following hip fracture, and we quantified the cost burden attributable to this prolonged LOS. Our finding supports the work of other authors who have noted a relationship between comorbidities and prolonged LOS and increased hospital costs following hip fracture ; howeverBecause there are currently no other published studies examining the relationship between the CCI score and LOS and hospital costs following hip fractures, we compared our findings with those reported for total joint arthroplasty. In the Tien et al.  study ofThere are several factors to consider in the interpretation of our results. First, the comorbidities of our patient population and the cost of inpatient care reflect the practice of a single, tertiary care, academic medical center, and further analysis is necessary to determine whether our findings are applicable to other surgical settings. Secondly, we only evaluated bundled payments that were related to the inpatient cost from the index procedure, and although this limitation does not affect our findings regarding the association between the CCI score and increased hospital costs, it is important to recognize that the cost burden we found represents the minimum additional cost incurred, and more research is needed to quantify the relationship between the CCI score and other factors which would affect hospital costs in a bundled payment model.The rationale for bundled payments is to incentivize various providers to collaboratively deliver high-quality care at the lowest possible cost, but several authors have noted potential downsides of this payment model, both for the patients and the providers. With respect to the former, Bozic et al.  noted th


The influence of psychological factors on acute neck pain is sparsely studied. In a secondary analysis of prospectively collected data, this study investigated how several psychological factors develop in the first three months of acute neck pain and how these factors influence self-perceived recovery.Patients were recruited in various chiropractic practices throughout Switzerland between 2010 and 2014. The follow-up telephone interviews were conducted for all patients by research assistants in the coordinating university hospital following a standardized procedure. The population of this study consisted of 103 patients  with a first episode of acute (<4 weeks) neck pain. Prior to the first treatment, the patients filled in the Bournemouth Questionnaire (BQ). One week and 1 and 3 months later, they completed the BQ again along with the Patient Global Impression of Change (PGIC). The temporal development (repeated measure ANOVA) of the BQ questions 4 (anxiety), 5 (depression), 6 (fear-avoidance) and 7 (pain locus of control) as well as the influence of these scores on the PGIC were investigated ).p = 0.013, R2 = 0.40 and p = 0.039, R2 = 0.63, respectively). Baseline depression , but not baseline anxiety, was a predictor for poor outcome. A high reduction in anxiety within the first month was a significant predictor for favorable outcome after 1 month .All psychological parameters showed significant reduction within the first month. The parameter ‘anxiety’ was associated with outcome at 1 and 3 months (Psychological factors emerged from this study as relevant in the early phase of acute neck pain. Particularly persistent anxiety and depression at baseline might be risk factors for a transition to chronic pain that should be addressed in the early management of neck pain patients. Neck pain is one of the leading causes for global years lived with a disability . In the It is widely established that psychological factors play an important role in chronic non-specific neck pain. Particularly anxiety, depression and catastrophizing seem to negatively affect pain intensity and disability in this patient group . AlthougThus, in order to prevent acute neck pain from becoming chronic, the goals of this study were to investigate how psychological factors  develop in the first 3 months after a first episode of acute neck pain, and how these psychological factors are associated with self-perceived recovery (assessed by PGIC). We hypothesized that i) the investigated psychological variables decreased in the first 3 months, ii) high psychological distress co-occurred with poor outcome, iii) high scores in the psychological variables at baseline were predictive for poor outcome, and iv) reduction in psychological distress led to favorable outcome.This study is based on the secondary analysis of data that were prospectively collected between 2010 and 2014 . For theEthical approval was obtained from the ethics committee from the Canton of Zurich, Switzerland (EK-19/2009) and all participants gave written informed consent prior to participation.Immediately prior to the first treatment, a numerical rating scale (NRS) for neck pain and a separate NRS  for arm pain were filled in by the patients. Furthermore, they answered a validated German version of the Bournemouth questionnaire (BQ) for neck pain –20. The The BQ questions 4 (anxiety), 5 (depression), 6 (fear-avoidance) and 7 (pain locus of control) were entered into the models as independent variables and were analyzed as continuous data. As for the PGIC, only the two scores “much better” and “better”, but not “somewhat better”, were considered a clinically significant change . Thus, tOne week after the first consultation, 75.6 %  of the patients reported clinically significant improvement. The percentage increased to 83.3 %  after 1 month and to 86.6 %  after 3 months.p < 0.001) significantly decreased from baseline to 1 week (p = 0.009) and from 1 week to 1 month (p = 0.001). Depression  = 17.25; p < 0.001) significantly declined between baseline and 1 week (p = 0.022) and 1 month to 3 months (p = 0.025). Fear avoidance  = 25.43; p < 0.001) and pain locus of control  = 17.15; p < 0.001) showed a significant reduction from 1 week to 1 month after onset of treatment .All tested psychological parameters showed significant reduction within the first month after onset of treatment, but only the parameter ‘depression’ further improved afterwards Fig. . AnxietyThe regression model with the psychological factors at each time point as independent variables and the concurrent self-reported outcome as dependent variable explained an increasing proportion of data variability up to 3 months. At 1 and 3 months after the first consultation, high scores in the parameter ‘anxiety’ were concurrent with poor self-reported outcome. The models showed good accuracy for discrimination between improved and unimproved patients at 1 month (AUC = 0.85) and excellent accuracy at 3 months (AUC = 0.98) Table .The psychological factors at baseline had no influence on the self-reported outcome at 1 week and 1 month. In the model that included only the psychological variables, high level of anxiety at baseline was somewhat predictive for favorable outcome at 1 month (AUC = 0.76). However, anxiety level at baseline became insignificant in the model that included age and baseline pain, where higher age emerged as a predictor for poor recovery (AUC = 0.74) Table . ConversA high reduction in anxiety between 1 week and 1 month after the first consultation was linked to a significantly higher chance for self-reported improvement at 1 month in both models Table  and the All psychological parameters that were investigated in this study improved during the first month. Depression declined only somewhat during the first week, but was the only parameter that still improved after the first month. Poor outcome at 1 and 3 months went along with high levels of anxiety. High baseline anxiety was not a risk factor for poor outcome, but its reduction during the first month was highly related to favorable recovery. In contrast, high level of depression at baseline was fairly related to poor recovery at 3 months.In order to prevent an acute neck pain episode from developing into a chronic problem, the reduction of anxiety at the beginning seems to be a key point in treatment even in this sample of patients who had not previously experienced neck pain. For recovery at 3 months, anxiety was of minor importance, but the factor depression became meaningful. Linton brought up in his review the temporal aspect of the influence of psychological factors on pain and hypothesized that different factors might be relevant at different time points in the course of neck and back pain . The finAnxiety and depression emerged from this study as the most important psychological factors for self-perceived recovery in the first 3 months of a first episode of acute neck pain. Accordingly, the study by Bot et al. on patients with acute neck and shoulder complaints reported that less vitality, which might be seen as a symptom of a depressive disorder, was related to poor recovery after 3 months . ContrarThe proportion of patients who reported clinically significant improvement was high (87 %), but well comparable with the numbers in the literature (5 to 10 % of neck problems become chronic ). HoweveThe strength of this study was that its data design allowed for analyzing not only the influence of psychological factors at certain time points, but also their development over time. Furthermore, the rather rigid inclusion criteria provided a homogeneous patient population and reduced bias resulting from symptom duration and previous pain episodes. However, of course, there were also several limitations. The major limitation of this study was the small number of patients that did not report improvement, which reduced power and might have hidden some findings. This limits generalizability of the results and implies that a confirmation of the results is needed. A second limitation was that the study did not control for the number and type of treatment that the patients underwent during the timespan when they were followed. However, the goal of this study was not to attribute the observed outcome to a certain treatment. The collected data rather reflect clinical practice, where the patients undergo individual treatment according to their needs. In addition, particularly in this sample of acute patients, the observed improvement might at least partly be attributed to natural history. Furthermore, this study did not assess information about other musculoskeletal complaints, although this is a known predictor for an unfavorable course of neck pain . Lastly,Psychological factors emerged from this study as relevant in the early phase of treatment of patients with a first episode of acute non-specific neck pain. A temporal development of these factors and their influence on self-reported outcome could be observed. Persisting anxiety in the early phase of an acute neck pain problem and depression at baseline emerged as risk factors for poor self-reported recovery and might thus contribute to the transition from acute to chronic pain. The clinical message of this study is that acute neck pain should be regarded as multidimensional. Clinicians should be aware that baseline depression and persisting anxiety might be risk factors for poor prognosis, which should be addressed in the early management of patients with acute non-specific neck pain.


There are two major theories describing the pathophysiology of migraines. Vascular theory explains that migraines resulted from vasodilation of meningeal vessels irritating the trigeminal nerves and causing pain. More recently, a neural theory of migraine has been proposed, which suggests that cortical hyperexcitability leads to cortical spreading depression (CSD) causing migraine-like symptoms. Chronic migraine requires prophylactic therapy. When oral agents fail, there are several intravenous agents that can be used. Understanding underlying causes of migraine pain would help to improve efficacy of migraine medications by changing their mechanism of action. Yet to date no study has been made to investigate the link between vascular changes in response to medications for migraine versus pain improvements. Functional near-infrared spectroscopy (NIRS) has been used as an inexpensive, rapid, non-invasive and safe technique to monitor cerebrovascular dynamics.In this study, a multi-distance near-infrared spectroscopy device has been used to investigate the cortical vascular reactivity of migraine patients in response to drug infusions and its possible correlation with changes in pain experienced. We used the NIRS on 41 chronic migraine patients receiving three medications: magnesium sulfate, valproate sodium, and dihydroergotamine (DHE). Patients rated their pain on a 1–10 numerical scale before and after the infusion.No significant differences were observed between the medication effects on vascular activity from near channels measuring skin vascularity. However, far channels—indicating cortical vascular activity—showed significant differences in both oxyhemoglobin and total hemoglobin between medications. DHE is a vasoconstrictor and decreased cortical blood volume in our experiment. Magnesium sulfate has a short-lived vasodilatory effect and increased cortical blood volume in our experiment. Valproate sodium had no significant effect on blood volume. Nonetheless, all three reduced patients’ pain based on self-report and no significant link was observed between changes in cortical vascular reactivity and improvement in migraine pain as predicted by the vascular theory of migraine.NIRS showed the potential to be a useful tool in the clinical setting for monitoring the vascular reactivity of individual patients to various migraine and headache medications. Neural and vascular theories are proposed as the main theories describing the pathophysiology of migraines . TraditiThere are a number of studies reported in the literature that suggest possible different cortical vascular responses between healthy individuals and migraine patients in different scenarios. In several of these studies, NIRS has been used as a non-invasive method of measuring cerebrovascular reactivity .2) signals acquired by NIRS are approximately two to five times higher in controls than migraine patients during four consecutive breath-holding tasks and concluded their results as a confirmation of an impaired cerebrovascular reactivity in the frontal cortex of migraine patients [2) of the right and left frontal lobes in response to intracranial pressure changes during the interictal period of migraine. According to their findings, the head-down maneuver resulted in a significantly smaller increase in right-sided total hemoglobin in migraineurs compared to volunteers. Moreover, it resulted in a small decrease in right-sided rSO2 and a significantly greater decrease in left-sided rSO2 in migraineurs compared to volunteers [2 and different hemoglobin balancing during breath-hold task have been reported for migraineurs. They have also concluded that migraineurs do not show marked vasodilation as a functional response to the CO2 increase [Akin et al. have shown that amplitudes of deoxygenated hemoglobin (Hb) and oxygenated hemoglobin , valproate sodium (12 patients) and dihydroergotamine (6 patients). We also correlate our findings with the subjects’ pain score self-reports. We aimed to investigate the utility of NIRS in comparing the analgesic efficacy of the above drugs based on patient self-reports compared with the measured cortical vascular reactivity in the clinical setting.2) and deoxyhemoglobin (Hb) molecules. There are other absorbents such as melanin and lipids; however, their overall average concentrations along the total optical path are negligible.Light in the near-infrared range (600–900 nm) penetrates the tissue because water, the key overall absorber of light in human tissue, has a low NIR absorption coefficient. In this range, tissue behaves as a turbid medium and light is significantly scattered by oxyhemoglobin , valproate sodium, and dihydroergotamine (DHE). DHE is a potent vasoconstrictor. It may constrict meningeal blood vessels causing symptomatic improvement consistent with the vascular theory. Magnesium sulfate has vasodilatory properties [We studied three commonly infused medications: magnesium sulfate  and topiramate seem to be more effective in migraine, as reported in the majority of controlled studies . ValproaThese infusions are required when commonly used oral prophylactic drugs are not effective. Typically magnesium sulfate was given first, valproate sodium next and DHE was given last.In this study, 41 patients  with an average age of 49.2 ± 9.5 years took part in a non-blinded trial using these medications; 21 subjects on magnesium sulfate, 12 subjects on valproate sodium and 8 subjects on DHE. Migraine subjects met the International Headache Society’s criteria for chronic migraine (ICHD-2) and were resistant to oral therapy. Patients rated their pain on a 1–10 scale (NRS-11) before and at the end of the infusion. The study was approved by the Drexel University Institutional Review Board (IRB) and informed consents and Ethics Committee approvals were obtained for all patients enrolled in the study, according to the Declaration of Helsinki.2 is extracted from the raw intensity data.Throughout the duration of the experiment, subjects were monitored by the NIRS probes that were attached to their foreheads. The probe configuration is shown in Fig. p1, Fp2 of the international 10–20 EEG system  During this time, we ensured that all external factors that could have significant effects on the NIRS measurements were constant and controlled for; these include light, movement and temperature. Experimental protocol is shown in Fig. Patients rated their pain on a 1–10 scale (NRS-11) before and at the conclusion of the infusion. Figure P ≤ 0.05) and were inherited from clinician’s policy of prescribing each drug. Average initial pain reported by patients for magnesium sulfate, valproate sodium and DHE was 4.4, 5.85 and 7.5, respectively. Magnesium sulfate was prescribed as an initial treatment and for patients with lower pain. Valproate sodium was used for patients whose pain was not improved by magnesium sulfate in previous sessions. If this was ineffective too, then DHE was considered. DHE was known to be more effective than magnesium sulfate and valproate sodium, and was prescribed for patients with higher pain. Based on self-reported pain scores, valproate sodium had a significant better pain improvement over magnesium sulfate (P = 0.03). However, self-reported pain score data do not show significant pain improvement between DHE and the other two drugs which could be the result of a small sample size.Reported initial pains were significantly different between medications (2) and deoxyhemoglobin (Hb) in the blood through Beer–Lambert law (Eqs. 2) during the course of DHE infusion. Total hemoglobin is summation of oxyhemoglobin and deoxyhemoglobin and is a measure of total blood volume.Data were collected from six channels for each subject—one near channel measuring vascular response of the skin and two far channels measuring vascular response from cortex and skin together on each side. Changes in the detected light intensity were converted to concentration changes of oxyhemoglobin , deoxyhemoglobin (Hb) and total hemoglobin (THb) data before and after the infusion. After removing faulty signals, the remainder of the data included 18 magnesium sulfate, 10 valproate sodium and 6 DHE subjects. Due to small sample sizes and non-normality of the data, Mann–Whitney U test (Wilcox test) was used to check if the difference in slope change between medications were significant.We examined the infusions’ effect on vascular reactivity. The extracted feature from the signal was slope of oxyhemoglobin  reflecting differences in cortical vascular reactivity among medications. In terms of slope changes in HbO2 and THb, we have the following order:No significant differences were observed between different medications on near channels which measure skin vascularity responses. This suggests that alternations in skin blood flow and autonomic response induced by drug infusion were not different between drugs. However, the analyses on far left channels showed significant differences in both HBO2, Hb and THb as measured by NIRS in an arbitrary unit for valproate sodium, magnesium sulfate and DHE as well as P values.Table In our experiments, near channels have penetration depth of 0.5 cm and measure alternations in skin vascular activity which are mostly caused by autonomic response. On the other hand, far channels capture up to 1.5 cm and measure cortical activities.Our results on far channels showed that DHE decreased blood volume, magnesium sulfate increased blood volume and valproate sodium had no significant effect on the blood volume. The near channels, measuring skin vascularity, showed no significant differences between the medications indicating that the results are not due to alteration in skin vascular activity.Although data were collected from six channels on both sides of forehead, significant differences in cortical activities between medications were only observed on the left side. Different left and right side cerebral reactivity in migraineurs has been reported before in literature as well. For instance,  reports However, the predominance side of pain  was not recorded in our data which makes it difficult to interpret.While these medications had significantly different effects on cortical vascular activities compared to each other, all three were effective in reducing the patients’ pain based on self-report. DHE, which is a well-known vasoconstriction, and MgSO4, which literature suggests causes cortical vasodilation, showed a decrease and an increase in blood volume, respectively; during our trial, yet they were both effective in improving pain and valproate sodium with no significant vascular effect had the best self-reported pain improvement among the medications.No significant link was observed between changes in cortical vascular reactivity and improvement in subjects’ self-reported pain scores.As explained briefly before there is no consensus about the underlying cause of migraine. It is possible that many factors may cause the class of headaches categorized as migraine. Neural and vascular theories are proposed as the main theories describing the pathophysiology of migraines . TraditiIn several studies, magnetic resonance angiography (MRA) has been employed to verify this theory. The method has been used to measure arterial changes before and after infusion of different vasoactive drugs and also before and during migraine headache attacks. However, the results are contradictory. The most recent study found intracranial but not extracranial arterial dilatation on the headache side relative to the non-headache side  while anIn another study, the effect of several vasodilators on meningeal arteries was investigated to find a connection between the effect of a substance on a meningeal vessel and its ability to artificially induce migraine. No clear correlation was found between the efficacy of a substance as a meningeal artery vasodilator in human and the ability to artificially induce migraine or the mechanism of action .More recently, consensus has shifted toward a neural theory of migraine which considers the excessive neocortical cellular excitability as the main cause. According to this theory, neuronal hyperactivity will cause cortical spreading depression (CSD) and then CSD will trigger a migraine attack. CSD involves rapid depolarization of cortical neurons with cellular efflux of potassium, in turn triggering migraine .Based on our results, no significant correlation was found between cortical vascular changes and pain improvement. Both medications that have different vascular effect (Mg and DHE) have improved pain the same and valproate sodium which has no effect on vascularity had the best pain improvement. So our data suggest that vascular theory may not explain the pain improvement mechanism in migraine patients completely.Our study had several limitations, which could be improved upon. We need a greater sample size of subjects (particularly DHE) to attain more statistically significant results. Subjects who had valproate sodium infusion can be interpreted as control subjects because the mechanism of the drug is such that it does not affect blood flow. However, it would be better to have control subjects with saline infusion only to control the effect of infusion itself on the data. Part of the significance of these results lies in the fact that the data were collected in a typical community pain clinic and not in a quiet research laboratory—speaking to the applicability of NIRS. Based on the work presented here, we believe that NIRS has the potential to be a useful tool in a clinical setting for assessing the vascular effects of various medications for headache and migraine. We believe that further technological improvement in NIRS hardware and signal analysis can make NIRS an even more useful tool for objective study and assessment of migraine. Furthermore, we hope that studies using NIRS can complement other measurements to facilitate the discussion about the underlying cause of the migraine headache.


DPYD) polymorphisms are associated with decreased enzyme activity and increased risk of fluoropyrimidine-related toxicity. In patients carrying non-functional DPYD variants , fluoropyrimidines should be avoided or reduced according to the patients’ homozygous or heterozygous status, respectively. For other common DPYD variants , conflicting data are reported and their use in clinical practice still needs to be validated. The high frequency of DPYD polymorphism and the lack of large prospective trials may explain differences in studies’ results. The epigenetic regulation of DPD expression has been recently investigated to explain the variable activity of the enzyme. DPYD promoter methylation and its regulation by microRNAs may affect the toxicity risk of fluoropyrimidines. The studies we reviewed indicate that pharmacogenetic testing is promising to direct personalised dosing of fluoropyrimidines, although further investigations are needed to establish the role of DPD in severe toxicity in patients treated for colorectal cancer.Fluoropyrimidines, the mainstay agents for the treatment of colorectal cancer, alone or as a part of combination therapies, cause severe adverse reactions in about 10%–30% of patients. Dihydropyrimidine dehydrogenase (DPD), a key enzyme in the catabolism of 5-fluorouracil, has been intensively investigated in relation to fluoropyrimidine toxicity, and several DPD gene ( Fluoropyrimidine-based therapy is used extensively in oncology for the treatment of many tumour types including gastrointestinal, breast and the aerodigestive tract cancers. 5-fluorouracil (5-FU) and its oral pre-prodrug capecitabine are the most commonly used chemotherapeutic agents either in monotherapy or in combination regimens . As it ovs. continuous infusion) [DPYD) mapping on chromosome 1p21.3 and consists of 23 exons [DPYD polymorphisms have been associated with decreased enzyme activity and increased risk of 5-FU severe toxicity. Low or deficient DPD activity was found in at least 3%–5% of individuals [DPYD polymorphisms and 5-FU toxicity is not yet clearly defined.The mechanism of action of the fluoropyrimidines comprises the inhibition of thymidylate synthase and the metabolic impairment of DNA and RNA by incorporation of drug metabolites; the mechanism of action is influenced by the different modes of administration of 5-FU (bolus nfusion) ,4,5. Thenfusion) . DPD is 23 exons . Most ofividuals  represenividuals . UnfortuDPYD*2A/c.1905+1G>A, *13/c.1679T>G, rs67376798/c.2846A>T) of the DPYD gene. Individuals homozygous or compound hererozygous for DPYD*2A, *13, rs67376798 can exeprience severe or even fatal toxicity. Homozygotes for nonfunctional DPYD*2A, *13 or rs67376798 variants have very low enzyme activity or are completely DPD deficient [DPYD variant alleles—with partial DPD deficiency [DPYD*2A, *13 or rs67376798 variants in all population is estimated to be <0.01  may influence outcomes. Toxicity may also be underestimated because of the intrinsic nature of the trials themselves as they tend to include patients with optimal perfomance status, low median age and liver laboratory tests within the normal ranges, thus minimising the risk of severe toxicity.This is a critical issue; whereas the genotyping of non-functional germline variations is strongly recommended to avoid toxicity, the absence of any of the variants does not equate with absence of DPD deficiency. The DPYD*2A in males compared with females (unadjusted OR = 20.96 vs. 9.74), in Caucasian patients, however the sex-gene interactions were not statistically significant [DPYD*2A will be proposed to investigate the observed difference between male and female DPYD*2A carriers. Regarding ethnicity, DPYD*2A and c.2846A>T variants are more frequent in Asian or European than in African populations, while the DPYD rs115232898 (Y186C) variant has been described only in African Americans patients with fluoropyrimidine related toxicity [Impact of sex and ethnicity on 5-FU related toxicity has been often investigated. Females experienced more severe toxicity than males during 5-FU treatment . Lee andnificant . FurtherDPYD undetected heritability, additional variants have been evaluated for DPD activity and associated fluoropyrimidine toxicity. Among them, DPYD c.496A>G, c.1129-5923C>G and c.1896T>C may have a role, but their use in clinical applications still needs to be validated.Based on the issue of DPYD and results in a methionine-valine (M166V) transition. This variant is quite frequent with an overall allele frequency of 7% and 12% in the European population (1000 Genomes Project Phase 1). The c.496A>G variant has been classified either as a variant which is related to DPD deficiency [in vitro studies [The allelic variant c.496A>G is located in exon 6 of ficiency  or as a  studies . The all studies . Loganay studies . Three a studies ,26,27. T studies .cis with c.1236G>A (E412E). Conflicting data exist about an association between c.1236G>A, and an increased risk of severe 5-FU-associated toxicity [Recently, the deep intronic variant c.1129-5923C>G was found to be significantly associated to severe 5-FU toxicity [toxicity ,28. Howetoxicity . Since ctoxicity .DPYD 1896T>C variant have increased 5-FU serum concentrations and a higher risk of treatment-related neutropaenia [Finally, a previous study showed that carriers of the ropaenia .UGT1A1*28 allele affects gene expression and leads to decreased glucuronidation of the irinotecan-metabolite SN-38 and increased risk of severe irinotecan-induced AE [UGT1A1 and DPYD may be particularly valuable in this setting; this is particularly true for CRC patients receiving triplet chemotherapy with fluoropyrimidines, oxaliplatin and irinotecan—with or without monoclonal antibodies. Recently, a FOLFOXIRI regimen achieved significantly superior outcomes as compared to standard doublet chemotherapy in terms of response rate, progression-free survival and overall survival [Diarrhoea and neutropaenia are the main toxic effects of irinotecan leading to dose-limitations and are also increased when the drug is associated with fluoropyrimidines. Since increased toxicity of chemotherapy combinations remains an unquestionable issue, patient management with adequate supportive measures is a priority for clinicians. The rational use of pharmacogenetics and the personalisation of dosing may allow safe administration of intensive regimens containing both irinotecan and fluoropyrimidines with maximisation of their therapeutic index . It is wduced AE ,34. Thussurvival . Initialsurvival  or in sesurvival . HoweverDPYD variations and receiving triplet chemotherapy with capecitabine, oxaliplatin and irinotecan—with bevacizumab or cetuximab [DPYD functional variants in association with the UGT1A1*28 allele. We observed a significant association (p = 0.021) between DPYD c.496 G risk allele and grade 3–4 chemotherapy-induced adverse events (AEs), with an OR of 4.93 . Using multivariate analysis, we confirmed an independent association of the DPYD c.496A>G variant with severe toxicity (p = 0.022). Also the UGT1A1*28/*28 homozygous status and the DPYD c.1896T>C variant showed a clinically significant association with severe toxicity. We however did not detect any significant association of the DPYD c.1129-5923C>G variant with severe toxicity, probably due to the small sample size [We recently carried out a pharmacogenetic study in 64 advanced CRC patients lacking non-functional etuximab . We simuple size .DPYD variants. Our analysis provides also a rational approach that opens new windows for investigation. Intensive regimens such as FOLFOXIRI could be reassessed in selected patients populations, such as those with DPYD c.496A>G and/or c.1896T>C variants, within the context of a Phase 1b dose-finding study. The validation of results in a prospective large trial is also necessary so that patients at highest risk of toxicity are pre-emptively identified. Genome-wide association studies and next-generation sequencing technologies in large cohorts may strengthen results obtained by candidate gene studies and identify new common or rare risk variants.Our strategy allowed us to reveal at least part of the genetically-based toxicity which goes undetected in the assessment of only the guideline-recommended non-functional DPYD gene are insufficient to explain differences in DPD expression and 5-FU sensitivity. Part of the variable activity of DPD may instead be explained by epigenetic factors; indeed methylation of the promoter, as well as its regulation by microRNAs, (miRNAs) has been shown to occur in DPYD.As revealed from the data reported above, variant alleles in the in vitro study, Noguchi and colleagues found that DPD activity was in part controlled by aberrant methylation of the DPYD promoter region which acted as a repressor of DPYD expression [in vivo study in a small series of clinical samples from DPD-deficient volunteers and DPD-deficient cancer patients, Ezzeldin and colleagues [DPYD promoter region is associated with down-regulation of DPD activity. A more recent study that assessed the methylation status of the DPYD promoter region by quantitative methylation-specific Polymerase Chain Reaction (PCR) in gastrointestinal cancer patients failed to establish an association of methylation with 5-FU severe toxicity [In an pression . In an illeagues  confirmetoxicity . AdditioIn vitro experiments confirmed that the overexpression of miR-27a and miR-27b in colorectal carcinoma cells reduces DPD expression [Recent data in lung tumours have suggested that differences in DPD expression may be arise as a consequence of miRNAs post-transcriptional regulation of the promoter . In vitrpression . In the pression .et al. [DPYD risk variant carriers, the rs895819 genotype may influence fluoropyrimidine toxicity risk. In particular, they found that the correlation of rs895819A>G with fluoropyrimidine toxicity depended on DPYD risk variant carrier status so that patients carrying both rs895819G and a DPYD risk variant had a strongly increased risk of toxicity. Conversely, in the absence of DPYD variants, rs895819G was related to a modest decrease in toxicity risk.We also investigated rs895819 in colorectal cancer patients receiving triplet chemotherapy detecting significant association with 3–4 grade toxicity at least in univariate analysis, not confirmed at the multivariate analysis. Recently, Amstutz et al.  suggesteDPYD*2A, *13 and c.2846A>T variants.Fluoropyrimide-based therapies are the standard of care for colorectal cancer patients. In patients with DPD deficiency, 5-FU can cause profound toxicity, such as mucositis, myelosuppression, hand-foot syndrome and diarrhoea. Pharmacogenetics-guided dosing is recommended only for the DPYD genetic variants, data are lacking and conflicting. Further research is needed to determine the optimal treatment strategy for patients carrying these DPYD risk alleles. Differences between results of studies can be explained by geographic allele frequency variability, by heterogeneity in toxicity assessment and time-points used, and by the heterogeneity in the 5-FU-based chemotherapy regimens. Given the common administration of fluoropyrimidine in combination therapy, investigation of the impact of concomitant cytotoxic drugs on toxicity risk may be enhanced in patients with and without DPYD risk variants.For the other common DPYD variants and UGT1A1*28 allele could be a strategy for dose personalisation. UGT1A1*28 allele can increase the risk of severe irinotecan-induced neutropaenia contributing to the toxicity of a doublet regimen [DPYD*2A and UGT1A1*28 with concomitant use of fluoropyrimidine and irinotecan can increase toxic effects, resulting also in lethal outcomes in these patients [For example, considering that 5-FU is often combined with irinotecan, concomitant assessment of  regimen . It is rpatients . Fluorop


Local steroid injections are common for treatment of impingement syndrome. Corticosteroid injections methods are basically in two formats, blind or with image guidance. The aim of this study is to compare the effect of ultrasound-guided in comparison with blind corticosteroid injections in patients with impingement syndrome. This study is a randomized clinical trial study undertaken in patients with diagnosis of impingement syndrome done in Isfahan University of Medical Science clinics from February 2014 to February 2015. The number of all patients registered in the study is 48; and then 40 patients were allocated to either control group randomly which received blind steroid injection or case group that underwent ultrasound-guided steroid injection. The clinical symptoms were assessed using Shoulder Pain and Disability Index (SPADI) questionnaire, Visual Analogue Scale (VAS) and shoulder range of motion (ROM) using goniometer at baseline and six weeks after the injection. Data analysis revealed a significant difference in the mean of the VAS, SPADI and shoulder ROM in both groups 6 weeks after intervention (P < 0.05). Patients with ultrasound guided corticosteroid injection had statistically significant improvements in function and shoulder ROM  compared to blind injection group after 6 weeks (P<0.05). There was not significant differences in pain (VAS) and internal and external rotation between these two groups (p>0.05). Our findings suggest that US image guided can improve the shoulder function of patients with impingement syndrome, and thus can be considered in comprehensive care programs of these patients for fast speed of rehabilitation. Painful shoulder problems are so common, as they are one of the main reasons of impaired function and statistically reported for 1 in 3 adult patients , accountSubacromial impingement syndrome (SIS) is the most usual cause of shoulder pain with affecting one-half of all shoulder pain sufferers . SIS is Many non-operative treatments have been advocated for treatment of subacromial impingement syndrome, including rest, active physiotherapy, non-steroidal anti-inflammatory drugs (NSAIDs), electrotherapy or cryotherapy . Corticosteroid injections are widely used to treat shoulder pain irrespective of the underlying etiology. The injections might be done in “blind” form which is via anatomical landmarks to guide placement a needle; or by using image guidance. Ultrasound (US) is a safe, effective imaging tool to guide musculoskeletal injections into the intended anatomical space .Studies have shown that the more accurate image guidance is than of needles placement . HoweverThis study used a randomized clinical trial study method and was undertaken in Physical medicine and rehabilitation outpatient clinics in Isfahan University of Medical Science  from February 2014 to February 2015. Patients were diagnosed based on clinical criteria, which were also confirmed by ultrasounds and x-rays for ruling out osseous pathology. 1) Posterolateral shoulder pain, 2) Pain in abduction or painful restriction of glenohumeral mobility, 3) provocation of symptoms by Neer and Hawkins tests.Exclusion criteria were as follows: shoulder pain due to osseous pathology , duration of shoulder pain more than three months, previous trauma in the shoulder region, previous physiotherapy or local steroid injection in last three months, any evidence of predisposing condition such as diabetes mellitus, rheumatoid arthritis, hypothyroidism and unwillingness to participate in the present study.In total, 48 patients fulfilled the inclusion criteria of the study and were used for the study. Eight patients were excluded from the study due to predisposing conditions including diabetes (N=3), and unwillingness to participate in this study (N=5). Participants were randomly assigned to control and case groups, two groups of 20 subjects, using randomized allocation. In the each group patients received 40 mg methylprednisolone with 1cc lidocaine 2%. Posterior approach was used for subacromial bursa injection in anatomical (blind) method, In this way needle is placed approximately 2 cm below posterior-lateral of acromion and the needle guided forward and slightly to the left under the acromion.In the second group corticosteroid injections were performed under ultrasound guidance. For subacromial bursal injection we used the lateral approach by using ultrasound equipment with high frequency linear transducer for guidance the probe is disinfected using the same disinfectant which is applied to the patient’s skin. The transducer was held in one hand and the syringe with 5 cm long needle caliber 23 Gauge in the other hand. The probe was positioned parallel to the long axis of the supraspinatus. The skin was punctured at a distance of about 2–3 cm from the probe in order to avoid contact between the needle and the probe. As soon as the needle had penetrated the subcutaneous tissues, its progress was real-time monitored on the US image. The needle was visualized as a hyperechoic structure with posterior comet-tail artifact. Progress of the needle until the tip had entered the subacromial bursa was observed. When the tip of the needle appeared to be inside the subacromial bursa, a small amount of liquid is injected to confirm the correct position (fluid passing from the needle tip into the bursa). The injection can be visualized in real-time as a spreading “cloud” of hyperechoic echoes inside the bursa .The end points in the present study were changes in the Visual Analogue Scale (VAS) score for assessing pain severity (0 to 10), and the Shoulder Pain and Disability Index (SPADI), a scale for assessing pain and limitation of shoulder function from baseline and 6 weeks after intervention. The SPADI questionnaire instructed as a self-administered instrument, which its main purpose is to measure pain by using five items, and disability, using eight items, associated with shoulder complaints. The five items for pain included zero for “not any pain” and score 10 for “the worst pain”. Respectively, for the eight disability items, “no difficulty” received the score of zero and “difficulty requiring assistance” received the score of 10. The SPADI has good internal consistency, test-retest reliability, and criterion and construct validity. It can also detect change in patient status over time. Therefore, the SPADI can be a useful instrument both in clinical practice and in clinical research . ShouldeThis study had the approval of the ethics Committee of Vice Chancellor for Research of Isfahan University of Medical Sciences, projection no394037. All participants received trial information and provided written informed consent prior to participation in the research. In addition to that, the confidentiality of all information was strictly safeguarded by the researchers.Study data were analyzed using the PASW Statistics 21 (IBM SPSS). Independent t-test carried out for compare the mean of Visual Analogue Scale (VAS), Shoulder Pain and Disability Index (SPADI) questionnaire, internal rotation and external rotation, flexion and abduction in two groups. Also, paired t-test was used to determine the effectiveness of USG injection and blindly injection in variables Visual Analogue Scale (VAS), Shoulder Pain and Disability Index (SPADI) questionnaire, internal rotation and external rotation, flexion and abduction at the first and six weeks after the injection. In all calculation P< 0.05 was consider as significant.This study used 40 patient participants, 20 patients in the blind injection group and 20 patients in the US-guided injection group. The participants were evaluated for the outcomes 6 weeks after the intervention.The mean age of patients in US-guided injection group was 50.4±6.78 years with a range of 38 to 64 years, of whom 12 (60%) patients were female and 8 (40%) patients were male and mean body mass index (BMI) was 27.05±2.21. The blinded injection group consisted of 13 female (65%) and 7 (35%) male. The mean age of these patients was 52.3±7.48 years with a range of 41-65 years and mean BMI 26.03±3.11 recorded. No significant difference is observed in the demographic data between the two groups at the beginning of trial (P >0.05) indicating the success of randomization .1. P-values show the differences between the two groups. These are resulted from independent-sample t test.The mean and standard deviation of Visual Analogue Scale (VAS), pain and disability scores of SPADI questionnaire, flexion, and abduction, internal, and external rotation are summarized in 1 values show the differences after and before the study in each group and are resulted from paired sample t test.P2 values show the differences between the two groups and are resulted from independent sample t test.PIn comparison of between two groups, US guided group experienced significantly better improvement in disability score of the SPADI questionnaire (p=0.01), abduction (p=0.01) and flexion (p=0.04), and significant differences was not seen in pain (VAS) (p=0.45), pain scores of SPADI questionnaire (p=0.34), internal rotation (p=0.73) and external rotation (P=0.92) between the two groups .Musculoskeletal Ultrasound has become so common as the result of improved technology and better resolution to guide environmental joints and soft tissue injection. US has the unique advantage of being able to visualize soft tissues, bony land-marks, and the needle with real-time scanning, thereby allowing dynamic visualization . AlthougThe aim of this study was to assess the efficacy of Ultrasound -guided versus blind corticosteroid injections in improving pain and function in patients with impingement syndrome. Our results showed that patients received ultrasound -guided steroid injection had significantly better improvement in function. Among ROM, shoulder flexion and abduction showed improvement in the US-guided group compared to the control group.US-guided corticosteroid injection had superior efficacy when compare to blind injection at least in shoulder function. This result was confirmed by shoulder flexion and abduction evaluation. However, US-guided corticosteroid injection was as effective as blind injection in respect to shoulder pain and other ROM parameter.In 2004, Naerdo et al studied 41 patients with painful shoulder. Patients were randomized to receive a blind subacromial injection (n = 20) or a sonographic guided injection (n = 21). Six weeks after injection, the VAS and the SFA (Shoulder function assessment) score showed a significantly greater improvement in sonographic guided injection group compared with blind group .In study of Ucuncu et al, in 2009 a total 60 consecutive patients with shoulder pain was enrolled, and randomly assigned to either by landmark-guided (n=30) or USG guided (n=30) injection. Clinical assessment included VAS for pain, the Constant scale for function, passive and active shoulder ROM with goniometric evaluation. Six weeks later the VAS and the Constant score showed a significant improvement in USG group compared with landmark-guided group. There were significant improvements in both active and passive ROM .On the other hand, there was some evidence that did not demonstrate benefits in the US–guided steroid injection group compared to the control group . In 2012Other studies suggested that possible therapeutic mechanisms of local steroid injections on impingement syndrome include anti-inflammatory effects, relaxation of reflex muscle spasm, pain relief, mechanical improvement and the placebo effect .The small sample size of study would not allow elaboration of the efficacy of ultrasound guided injection. To determine long-term effects of the technique and also to compare ultrasound guided steroid injection to other conservative management of impingement syndrome further research is needed.The results of this study shows that US-image guided method can improve the overall shoulder function of patients with impingement syndrome, thus, it can be suggested to special programs for fast speed rehabilitation of these patients.We can list the advantages of this study as following:1) This study has been done in a radiologist clinic with the help of an experienced sonography soft texture.2) There is no similar study in the studies population.3) Results of this study show that, which are in line with other studies, that ultrasound-guided injection increases accuracy but it does not have a significant impact on efficacy, especially in cases where there are limitations to ultrasound.


NCT01955967.Trigeminal neuralgia is the most common neuralgia. Its therapeutic approach is challenging as the first line treatment often does not help, or even causes intolerable side effects. The aim of our randomized double blind, placebo controlled, crossover study was to investigate in a prospective way the effect of lidocaine in patients with trigeminal neuralgia. Twenty patients met our inclusion criteria and completed the study. Each patient underwent four weekly sessions, two of which were with lidocaine (5 mgs/kg) and two with placebo infusions administered over 60 minutes. Intravenous lidocaine was superior regarding the reduction of the intensity of pain, the allodynia, and the hyperalgesia compared to placebo. Moreover, contrary to placebo, lidocaine managed to maintain its therapeutic results for the first 24 hours after intravenous infusion. Although, intravenous lidocaine is not a first line treatment, when first line medications fail to help, pain specialists may try it as an add-on treatment. This trial is registered with  Trigeminal neuralgia (TN) is the most common neuralgia, with an annual incidence of 5/100000 [Treatment guidelines, published from the American Academy of Neurology (AAN) and the European Federation of Neurologic Societies (EFNS), recommend carbamazepine or oxcarbazepine as the first choice pharmacological treatment of TN and baclofen or lamotrigine as the second choice . HoweverLidocaine is a common amino amide-type local anesthetic and antiarrhythmic drug . It is mIn the literature, only few retrospective studies of the effect of intravenous lidocaine on TN exist. The aim of our randomized double blind, placebo controlled, crossover study was to investigate in a prospective way the effect of lidocaine in patients with TN.Following the approval of the Institutional Ethical Committee of Aretaieion Hospital, University of Athens, all consecutive patients suffering from TN who visited the Outpatient Pain and Palliative Care Center were invited to participate in the study.To be enrolled, the patients had to meet the following inclusion criteria: (1) confirmed diagnosis of TN according to IASP definition, (2) age equal to or greater than 18 years, (3) visual analogue scale (VAS) score equal to or greater than 3 (out of a maximum 10), (4) Douleur Neuropathique 4 Questionnaire (DN4) score equal to or greater than 4 (out of a maximum 10), (5) having received the recommended medications for TN  for an adequate period without therapeutic results, (6) TN duration of at least 12 months, (8) no history of allergy to lidocaine, (9) no history of substance abuse, (10) absence of severe psychiatric diseases, (11) not being pregnant, (12) not lactating, (13) absence of severe cardiac, hepatic, and renal decease, and (14) be willing to provide a written informed consent to undergo the experimental procedures.Each patient participated in four sessions, every 2nd day, receiving two active and two placebo treatments, involving continuous infusion of 1 hour. Active treatment was lidocaine (5 mg per kilogram of body weight) in 250 mL of 5% dextrose solution and placebo treatment was 250 mL of 5% dextrose solution.Subjects were randomly assigned to treatment sequence via a computer-generated randomization list. A randomization list was prepared in sealed envelopes for each patient. Investigator A was responsible for solution preparation according to the randomization list. Investigator B, who was blind to the treatment, was responsible for clinical examination and treatment administration. At the end of each treatment investigator B had to record data and enclose the forms in envelopes that remained closed until the end of the study.In the morning of each session (08:00) the patients were guided to a calm and separate room where investigator B recorded the pain intensity on VAS before the beginning of the infusion and at the end of it. Moreover, investigator B tested the intensity of (1) mechanical allodynia (pressure of the painful area by an unused pencil), (2) thermal allodynia , (3) cold allodynia , (4) pinprick hyperalgesia , (5) hot hyperalgesia , and (6) cold hyperalgesia .During the sessions the patients were monitored continuously by 3-lead electrocardiogram, pulse oximetry, and blood pressure (BP) manometer. Every 15 minutes systolic BP, diastolic BP, oxygen saturation, and heart rate (HR) were recorded. Any side effects, such as somnolence, mental confusion, metal taste, tingling sensation around the mouth, vision disturbances, tremor, drowsy mouth, tremor, or anything else were also documented.Finally, at the end of each session the patients were given a “Pain Diary,” where they recorded the VAS score at 16:00, 20:00, and 24:00 the same day and at 08:00 the next morning.t-tests for normally distributed continuous data and Mann-Whitney's U test for nonnormally distributed data.A database was developed using the Statistical Package for Social Science . Frequencies and descriptive statistics were examined for each variable. Comparisons between patients who received lidocaine and patients who received placebo were made using Student's Allodynia and hyperalgesia were graded according to a Likert scale from 0 to 4 . Grading scores in allodynia and hyperalgesia before and after intravenous administration were recorded. Patients who achieved a reduction of at least 1 grading point in the Likert scale were considered to have achieved a reduction of allodynia and hyperalgesia, when patients who either graded the same before and after or showed increase in the Likert scale were considered not to have achieved a reduction. Comparisons between the lidocaine and placebo groups regarding these categorical data were made using the chi-square test.Power analysis demonstrated that a 20% difference in VAS reduction with 80% power could be detected with a sample of 20 patients.P < 0.05 was considered to be statistically significant.A value of Between February 2007 and September 2011, 23 individuals fulfilled the above-mentioned inclusion criteria. However, three patients denied continuing after the first session. Therefore, our final study population consisted of twenty patients. Clinical and demographic characteristics of the study total population are summarized in P < 0.001). This was maintained for at least 24 hours after treatment as was documented in the pain diary. Hence, at 24 hours after treatment lidocaine achieved a reduction of 52% of the pretreatment intensity of pain when patients who received placebo reported a mild increase of 4% of the pretreatment intensity of pain . Therefore the effectiveness of different doses remains unstudied. Future clinical research should focus on identifying the least effective dosage of intravenous lidocaine.Intractable TN remains a difficult to manage type of neuropathic pain. Interventional procedures, such as microsurgical decompression, have good results in many patients . However