Combination of Pain Location and Pain Duration is Associated with Central Sensitization-Related Symptoms in Patients with Musculoskeletal Disorders: A Cross-Sectional Study.

OBJECTIVES: Increased evidence indicates that pain location affects central sensitization (CS)-related symptoms. In addition, pain location and pain duration may be intricately related to CS-related symptoms. However, these factors have been investigated separately. This study aimed to investigate the association between CS-related symptoms and pain location and/or pain duration in patients with musculoskeletal disorders. METHODS: Six hundred thirty-five participants with musculoskeletal disorders were included in this cross-sectional study. All participants were assessed for pain location, pain duration, central sensitization inventory (CSI), EuroQol-5 dimension, and brief pain inventory. The participants were categorized into 3 groups based on pain location (spinal, limb, and both spinal and limb pain) and into 2 groups based on pain duration (acute and chronic pain). RESULTS: The interaction between pain location and pain duration were not significant on CSI score (P > 0.05). The odds ratio for higher CSI score (≥ 40) in patients with both spinal and limb pain vs. those with spinal or limb pain was 2.64 (P < 0.01) and that in patients with chronic pain vs. those with acute pain was 1.31 (P = 0.52). In addition, the prevalence of higher CSI scores in the combination of chronic and "both spinal and limb" pain was high (23.1%, adjusted residual = 4.48). CONCLUSIONS: Pain location independently influenced CSI scores, and the combination of both spinal and limb pain and chronic pain indicated high CSI scores. The combination of pain location and pain duration is an important clue that points to CS-related symptoms.

Validation of the Japanese version of the life satisfaction checklist (LiSat-11) in patients with low back pain: A cross-sectional study.

BACKGROUND: Previous studies suggest that life satisfaction assessment using the Life Satisfaction checklist (LiSat-11) is a meaningful outcome measure and may play an important role in setting rehabilitation goals in patients with chronic pain. Until now, there was no Japanese version of this questionnaire, and the psychometric properties of the original version of the LiSat-11 have only been investigated using classical test theory approaches. The objective of the present study was to evaluate the psychometric properties of the LiSat-11-J using Rasch analysis in a sample of Japanese people with low back pain (LBP). METHODS: One hundred and two participants with LBP completed the LiSat-11-J. Concurrent Validity of the LiSat-11-J was investigated by examining the relationships between the LiSat-11-J and clinical valuable. Rasch analysis was used to assess targeting, category ordering, unidimensionality, person fit, internal consistency, and differential item functioning. RESULTS: The LiSat-11-J was significantly correlated with disability, pain-related catastrophizing, fear of movement, anxiety, and depression. The LiSat-11-J targeted the participants with low life satisfaction and had unidimensionality, good internal consistency, and good test-retest reliability. Responses to category 1 ("very dissatisfying") and 2 ("dissatisfying") were disordered. After collapsing these two categories into a single new category, targeting function and category order showed a little improvement. CONCLUSION: The LiSat-11-J has unidimensionality, acceptable internal consistency, good test-retest reliability, and concurrent validity to the assessment of pain-related disability and psychological factors. However, targeting function and category order were not well. These two components showed improvement by rescoring category, but not sufficient. These results suggest that the LiSat-11-J is not well adequate to apply as an assessment tool of life satisfaction to the patients with LBP.

Psychometric properties of the Japanese version of short forms of the Pain Catastrophizing Scale in participants with musculoskeletal pain: A cross-sectional study.

BACKGROUND: The Pain Catastrophizing Scale (PCS) is a commonly used as measure of pain catastrophizing. The scale comprises 13 items related to magnification, rumination, and helplessness. To facilitate quick screening and to reduce participant's burden, the four-item and six-item short forms of the English version of the PCS were developed. The purpose of the present study was to evaluate the psychometric properties of a Japanese version of the short forms of PCS using a contemporary approach called Rasch analysis. METHODS: A total of 216 patients with musculoskeletal disorders were recruited in this study. Participants completed study measures, which included the pain intensity, the Pain Catastrophizing Scale (PCS), and the Tampa Scale of Kinesiophobia (TSK). Furthermore, the four-item (items 3, 6, 8, and 11) and six-item (items 4, 5, 6, 10, 11, and 13) short forms of the Japanese version of PCS were measured. We used Rasch analysis to analyze the psychometric properties of the original, four-item, and six-item short forms of PCS. RESULTS: Rasch analysis showed that both short forms of PCS had acceptable internal consistency, unidimensionality, and no notable DIF and were functional on the category rating scale. However, four-item short form of PCS had two misfit items. CONCLUSIONS: Six-item short form of PCS has acceptable psychometric properties and is suitable for use in participants with musculoskeletal pain. Thus, six-item can be used as brief instruments to evaluate pain catastrophizing.

Successful Graded Mirror Therapy in a Patient with Chronic Deafferentation Pain in Whom Traditional Mirror Therapy was Ineffective: A Case Report.

A 43-year-old man had deafferentation pain in his right upper extremity secondary to brachial plexus avulsion from a traffic accident 23 years previously. On our initial examination, he had severe tingling pain with numbness in the right fingers rated 10 on the numerical rating scale. The body perception of the affected third and fourth fingers was distorted in the flexed position. Although he performed traditional mirror therapy (TMT) for 4 weeks in the same methods as seen in previous studies, he could not obtain willed motor imagery and pain-alleviation effect. Therefore, we modified the task of TMT: Graded mirror therapy (GMT). GMT consisted of five stages: (1) observation of the mirror reflection of the unaffected side without imagining any movements of the affected side; (2) observation of the mirror reflection of the third and fourth fingers changing shape gradually adjusted from a flexed position to a extended position; (3) observation of the mirror reflection of passive movement; (4) motor imagery of affected fingers with observation of the mirror reflection (similar to TMT); (5) motor imagery of affected fingers without mirror. Each task was performed for 3 to 4 weeks. As a result, pain intensity during mirror therapy gradually decreased and finally disappeared. The body perception of the affected fingers also improved, and he could imagine the movement of the fingers with or without mirror. We suggested that GMT starting from the observation task without motor imagery may effectively decrease deafferentation pain compared to TMT.

[Alogliptin].

Alogliptin, a dipeptidyl peptidase-4(DPP-4) inhibitor, is launched in Japan in advance of other countries in the world. Alogliptin has high-selectivity to inhibit DPP-4 activity compared to other DPP-4 inhibitors due to its unique formula of chemical structure. Clinical studies provided evidences that alogliptin monotherapy with daily doses of 12.5 and 25 mg decreased the HbAlc level approximately 0.4-0.8% accompanied with an elevation of active glucagon-like peptide(GLP)-1 level. Neither body weight change nor apparent adverse events was observed. In type 2 diabetic patients who already treated with pioglitazone or voglibose, addition of alogliptin further decreased HbAlc by 0.9% from basal level during 12-week study period. Here, we entirely reviewed pharmacological and clinical profiles of alogliptin by introducing preclinical and clinical studies conducted inside and outside of Japan.

Comparison of the effects of three kinds of glucose-lowering drugs on non-alcoholic fatty liver disease in patients with type 2 diabetes: A randomized, open-label, three-arm, active control study.

AIMS/INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is often observed in individuals with type 2 diabetes mellitus, and it is known that the presence of type 2 diabetes mellitus leads to the aggravation of NAFLD. The aim of this study was to compare the possible effects of three kinds of oral hypoglycemic agents on NAFLD in individuals with type 2 diabetes mellitus. MATERIALS AND METHODS: We carried out a prospective clinical trial (a randomized and open-label study) in patients with type 2 diabetes mellitus and NAFLD. A total of 98 patients were randomly allocated either to the dapagliflozin (n = 32), pioglitazone (n = 33) or glimepiride (n = 33) group, and the patients took these drugs for 28 weeks. The primary end-point was the change of the liver-to-spleen ratio on abdominal computed tomography. RESULTS: There was no difference in baseline clinical characteristics among the three groups. Dapagliflozin, pioglitazone and glimepiride ameliorated hyperglycemia similarly. Bodyweight and visceral fat area were significantly decreased only in the dapagliflozin group. Serum adiponectin levels were markedly increased in the pioglitazone group compared with the other two groups. Dapagliflozin and pioglitazone, but not glimepiride, significantly increased the liver-to-spleen ratio, and the effects of dapagliflozin and pioglitazone on the liver-to-spleen ratio were comparable. CONCLUSIONS: The present study showed that the decrease of visceral fat area and the increase of adiponectin level contributed to the improvement of NAFLD in patients with type 2 diabetes mellitus. Furthermore, dapagliflozin and pioglitazone exerted equivalent beneficial effects on NAFLD in patients with type 2 diabetes mellitus, although it seemed that these two drugs had different mechanisms of action.

The central sensitization inventory predict pain-related disability for musculoskeletal disorders in the primary care setting.

BACKGROUND: Central sensitization (CS) is found in patients with musculoskeletal disorders and is related to clinical symptoms, including pain-related disability. The Central Sensitization Inventory (CSI) has been developed for patients who are at risk of symptoms related to CS, and CSI severity levels are suggested for clinical interpretation of the CSI score. However, the longitudinal relationship between CSI severity and pain-related disability is unclear in primary care. In this study, we investigated the association between CSI severity levels and the profiles of patients with musculoskeletal disorders as well as the longitudinal relationship between CSI severity levels and pain-related disability in primary care settings. METHODS: A total of 553 patients were assessed using CSI, EuroQol-5 dimension (EQ5D), and Brief Pain Inventory (BPI). Of the 553 patients, 150 patients were reassessed at the 3-month follow-up. Patients were grouped into three severity levels according to baseline CSI score: subclinical, mild, and moderate to higher level. RESULTS: As the CSI severity levels increased, the clinical symptoms tended to worsen on cross-sectional analysis (p < 0.05). Pain-related disability at the 3-month follow-up was significantly higher for patients with moderate to high baseline CSI severity levels than for patients with subclinical baseline CSI levels (p < 0.001). Furthermore, pain-related disability increased according to the CSI severity level, with a medium to large effect size. However, there were no differences in pain duration across the CSI severity levels. CONCLUSIONS: CSI has clinical utility as a prediction tool regardless of pain duration in patients with musculoskeletal disorders in primary care settings. SIGNIFICANCE: Higher CSI severity levels predicted higher pain-related disability for patients with musculoskeletal disorders in a primary care setting. CSI is a clinically useful prediction tool in patients with musculoskeletal disorders.

Development and psychometric properties of short form of central sensitization inventory in participants with musculoskeletal pain: A cross-sectional study.

BACKGROUND: The central sensitization inventory (CSI) comprises 25 items and is commonly used to measure somatic and emotional symptoms related to central sensitization symptoms. CSI was developed as an easy-to-administer screening instrument for patients at high risk of developing central sensitization in whom it was essential to quickly evaluate the condition. The purpose of the present study was to develop a short form of CSI and evaluate its psychometric properties using a contemporary approach called Rasch analysis. METHODS: A total of 505 patients with musculoskeletal disorders were recruited in this study. The CSI, pain intensity, pain interference, and the health-related quality of life (QOL) were evaluated for each participant. The original CSI items were consecutively analyzed using the Rasch model. Successive Rasch analyses were performed until a final set of items satisfied the model fit requirements. We also analyzed the psychometric properties of the original and short forms of CSI. RESULTS: Four consecutive Rasch analyses identified the removable items. Finally, the shortest questionnaire obtained that maintained the correct psychometric properties based on the Rasch model contained only 9 items (CSI-9). Rasch analysis showed that the CSI-9 had acceptable internal consistency, exhibited unidimensionality, had no notable differential item functioning, and was functional on the category rating scale. CONCLUSIONS: The nine-item short form of CSI has acceptable psychometric properties and is suitable for use for patients with musculoskeletal pain. Thus, the CSI-9 can be used as a brief instrument to evaluate central sensitization.

Validation of the Japanese version of the Central Sensitization Inventory in patients with musculoskeletal disorders.

BACKGROUND: Many musculoskeletal pain conditions are characterized by hypersensitivity, which is induced by central sensitization (CS). A questionnaire, the Central Sensitization Inventory (CSI), was recently developed to help clinicians identify patients whose presenting symptoms may be related to central sensitivity syndrome (CSS). The aims of the present study were to examine criterion validity and construct validity of the Japanese version of the CSI (CSI-J), and to investigate prevalence rates of CS severity levels in patients with musculoskeletal disorders. METHODS: Translation of the CSI into Japanese was conducted using a forward-backward method. Two hundred and ninety patients with musculoskeletal pain disorders completed the resultant CSI-J. A subset of the patients (n = 158) completed the CSI-J again one week later. The relationships between CSI and clinical symptoms, EuroQol 5-dimension (EQ-5D) and Brief Pain Inventory (BPI), were examined for criterion validity. EQ-5D assesses Health-related QOL and BPI measures pain intensity and pain interference. The psychometric properties were evaluated with analyses of construct validity, factor structure and internal consistency, and subsequently investigate the prevalence rates of CS severity levels. RESULTS: The CSI-J demonstrated high internal consistency (Cronbach's α = 0.89) and test-retest reliability was excellent value (ICC = 0.85). The CSI-J was significantly correlated with EQ-5D (r = -0.44), pain intensity (r = 0.42), and pain interference (r = 0.48) (p < 0.01 for all). Ten percent of the participants were above the cutoff "40". The exploratory factor analysis resulted in 5-factor model. CONCLUSIONS: This study reported that the CSI-J was a useful and psychometrically sound tool to assess CSS in Japanese patients with musculoskeletal disorders. The finding of the prevalence rates of CS severity levels in patients with musculoskeletal disorders may help clinicians to decide strategy of treatment.

Hypoglycemic Coma Induced by the Use of Succinic Acid Cibenzoline in Frail Late-stage Elderly Subjects.

Succinic acid cibenzoline (CZ) is an antiarrhythmic agent often used for the treatment of tachyarrhythmia. However, hypoglycemia should be avoided in the treatment of diabetes. We herein report two late-stage elderly subjects who experienced a severe and prolonged hypoglycemic coma after the usage of CZ. These cases suggest that, when CZ is administered to elderly subjects with renal dysfunction and/or frailty, we should be aware of the possibility that this medicine may induce hypoglycemia and should adjust the dose as appropriate and monitor the concentration of CZ to avoid severe hypoglycemia.

Inadequate Triglyceride Management Worsens the Durability of Dipeptidyl Peptidase-4 Inhibitor in Subjects with Type 2 Diabetes Mellitus.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are often used all over the world and exert various beneficial effects including glucose-lowering effect in many subjects with type 2 diabetes. It is poorly understood, however, which factors are closely related with the durability of glucose-lowering effect by DPP-4 inhibitor. In this study, we examined retrospectively which factors could mainly influence the durability of DPP-4 inhibitor. We enrolled 212 participants with type 2 diabetes to whom DPP-4 inhibitor was administered for over 1 year without an addition or increase of other hypoglycemic agents. Age and baseline HbA1c level were significantly higher in the effective group than those in the ineffective group. The effective group had a tendency of smaller amounts of weight change, average total cholesterol, and average triglyceride compared with the ineffective group. Multiple logistic regression analysis showed that average triglyceride and baseline HbA1c were independent predictors associated with the durability of DPP-4 inhibitor. Moreover, an average triglyceride level contributed to the durability of DPP-4 inhibitor in the obese group (BMI ≥ 25 kg/m2) but not in the nonobese group (BMI < 25 kg/m2). These results suggest the importance of strict triglyceride management to maintain the durability of glucose-lowering effect by DPP-4 inhibitor, especially in obese subjects with type 2 diabetes.

Advanced breast cancer in a relatively young man with severe obesity and type 2 diabetes mellitus.

It is known that male breast cancer is extremely rare and obesity is a strong risk factor of breast cancer in both male and female. In general, the prognosis in breast cancer in males is known to be very poor compared to that in females as it tends to be more advanced stage due to delayed initial diagnosis. Therefore, we should be aware of the possibility that breast cancer could be developed even in relatively young males without any specific risk factors especially when the subjects have severe obesity.

Werner Syndrome and Diabetes Mellitus Accompanied by Adrenal Cortex Cancer.

Werner syndrome is a rare genetic disease characterized by progeria, diabetes mellitus, cataracts and various types of malignancy. However, there are few reports showing adrenal cortex cancer in subjects with Werner syndrome. We herein report an extremely rare case of Werner syndrome accompanied by adrenal cortex cancer. Based on the data obtained from blood samples, computed tomography, magnetic resonance imaging and 131I adosterol scintigraphy, we diagnosed this subject with adrenal cortex cancer and Cushing's syndrome. Since the prognosis of adrenal cancer is very poor, we should be aware of the possibility of adrenal cancer occurring in subjects with Werner syndrome.

Case of disseminated pyomyositis in poorly controlled type 2 diabetes mellitus with diabetic ketoacidosis.

Primary pyomyositis is a pyogenic and uncommon infection of skeletal muscle, which is mainly observed in tropical areas and/or human immunodeficiency virus patients. In non-human immunodeficiency virus infected patients, the most common cause is diabetes mellitus. Because of its rarity, the accurate diagnosis is often challenging. Staphylococcus aureus is the most common causative bacteria. According to the severity, pyomyositis is divided into three stages, and the late stage is occasionally lethal. The present case was compatible with the most advanced stage. Therefore, it was very difficult to save her life without precise and timely diagnosis. Furthermore, in the invasive stage, surgical drainage and broad-spectrum antibiotics should be given for a long enough period. Here, we report a case of a Japanese woman who developed disseminated abscesses under poorly controlled diabetic conditions accompanied by ketoacidosis, but was successfully treated without any sequelae.

Optimal cut-off value of alanine aminotransferase level to precisely estimate the presence of fatty liver in patients with poorly controlled type 2 diabetes.

Optimal cut-off value of ALT level to precisely estimate the presence of fatty liver was as low as 28.0 U/L. We should consider the possibility of fatty liver even when ALT level is within normal range in subjects with poorly controlled type 2 diabetes.

Clinical effects of liraglutide are possibly influenced by hypertriglyceridemia and remaining pancreatic ß-cell function in subjects with type 2 diabetes mellitus.

We searched for factors influencing the clinical effects of GLP-1 analogue liraglutide in subjects with type 2 diabetes. Multivariate analyses showed that hypertriglyceridemia and baseline HbA1c levels were independent predictors for the efficacy of liraglutide and that CPR index was an independent predictor for the durability of liraglutide.

Association of GA/HbA1c ratio and cognitive impairment in subjects with type 2 diabetes mellitus.

AIMS: The aim of this study was to search for factors influencing cognitive impairment and to clarify the association between the fluctuation of blood glucose levels and cognitive impairment in elderly Japanese subjects with type 2 diabetes. METHODS: We recruited 88 relatively elderly subjects (≥65years old) with type 2 diabetes who were hospitalized in Kawasaki Medical School from January 2014 to December 2015. We evaluated the fluctuation of blood glucose levels with glycoalbumin (GA)/hemoglobin A1c (HbA1c) ratio, and estimated cognitive impairment with Hasegawa dementia scale-revised (HDS-R) score and mini mental state examination (MMSE) score. RESULTS: Multivariate analyses showed that GA/HbA1c ratio and urinary albumin excretion, but not hypoglycemia, were independent determinant factors for cognitive impairment in elderly Japanese subjects with type 2 diabetes. CONCLUSIONS: The fluctuation of blood glucose levels per se is closely associated with cognitive impairment in elderly subjects with type 2 diabetes even when hypoglycemia is not accompanied. Since it is very easy to calculate GA/HbA1c ratio, we should check this ratio so that we can reduce the fluctuation of blood glucose levels especially in elderly subjects with type 2 diabetes.

Strawberry milk-like blood in a subject with diabetic lipemia: dramatic change to transparent color after insulin therapy.

INTRODUCTION: It is known that chylomicronemia is caused by several pathologies and is classified as primary and secondary chylomicronemia. Since hypertriglycemia is associated with an increased risk of cardiovascular disease and severe pancreatitis, it is very important to make a proper diagnosis of the cause of hypertriglycemia. CASE DESCRIPTION: We herein present the case of a 40-year-old male who developed severe hypertriglycemia accompanied with acute exacerbation of type 2 diabetes mellitus. On admission, his blood glucose level was 306 mg/dl and HbA1c was 12.5 %. Moreover, serum triglyceride level was elevated up to 5661 mg/dl. When blood was drawn, it presented strawberry milk-like color. After receiving insulin treatment, he obtained good glycemic control and the serum became back to normal transparent color. DISCUSSION AND EVALUATION: Insulin resistance reduces triglyceride clearance and also increases triglyceride release from adipocyte. It is known that glucose toxicity and strong insulin resistance induce inactivation of LPL, which results in chylomicronemia. CONCLUSION: This case report suggests that when serum triglyceride level is markedly elevated due to diabetic lipemia, it is extremely important to obtain good glycemic control.

Dramatic mitigation of bone pain after phosphorus replacement therapy in a subject with FGF23-related hypophosphatemic osteomalacia.

INTRODUCTION: Fibroblast growth factor 23 (FGF23) is secreted from bone and suppresses the absorption of phosphorus in renal proximal tubule and in intestinal tract. Therefore, the increase of serum FGF23 levels leads to hypophosphatemic situations. Tumor-induced osteomalacia is often induced by various tumors, but it is often difficult to identify the localization of tumor, because most of the FGF23-producing tumors are small and could be observed in any part of the body. CASE DESCRIPTION: Here we report a case of elderly female subject with FGF23-related hypophosphatemic osteomalacia who repeatedly experienced severe bone pain and fragility fracture in various parts of the body. Although we failed to identify the localization of tumor in this subject even with various examination, after starting phosphorus replacement therapy with relatively small amounts of calcium phosphate (1.5 g/day) (phosphorus content: 270 mg), hypophosphatemia was ameliorated and repeated bone pain was dramatically mitigated without any surgical operation. DISCUSSION AND EVALUATION: Even when we fail to identify the localization of tumor in subjects with FGF23-related hypophosphatemic osteomalacia, phosphorus replacement therapy for hypophosphatemia could reduce the bone pain. CONCLUSIONS: We should be aware of the possibility that phosphorus replacement therapy exert marked beneficial effects for the reduction of bone pain in subjects with FGF23-related hypophosphatemic osteomalacia even when we fail to identify tumor localization.

Are tactile acuity and clinical symptoms related to differences in perceived body image in patients with chronic nonspecific lower back pain?

Clinically, perceived image of the lower back and the two-point discrimination (TPD) test are used as markers for evaluating alterations of cortical reorganization. The purpose of the present study was to examine whether TPD and selected clinical findings are different in subgroups of individuals with chronic nonspecific lower back pain (CNLBP) based on body image drawings. Forty-two patients with CNLBP and seventeen healthy individuals were recruited. Perceived body image, TPD and clinical profiles was measured. Of the patients with CNLBP, 42.8% had a normal perceived body image, 28.5% an expanded image, and 28.5% a shrunken image. The TPD distance threshold was significantly larger for the expanded subgroup (13.3 ± 6.8 mm) compared with the control (5.5 ± 3.8 mm; Difference, 7.8; 95%CI, 1.83 to 13.66; p < 0.05) and normal subgroups (4.5 ± 5.5 mm; Difference, 8.8; 95%CI, 2.90 to 14.59; p < 0.05). No significant differences in pain intensity, duration of pain, Roland Morris Disability Questionnaire (RDQ), and Pain Catastrophizing Scale (PCS) scores were found between three body image subgroups. Our results suggest that TPD is increased in patients who report an expanded perceived image of the lower back compared with healthy individuals and patients who report a normal image. The effectiveness of new rehabilitation techniques may be evaluated by assessing perceived image of the lower back and TPD values for patients with CNLBP before and after treatment.