1.Study on blood ammonia in terminally ill cancer patients
Yoshiyuki Kodama ; Tetsuo Konishi ; Yasuhiro Nagaoka ; Hiroya Kitai ; Keisuke Aoki
Palliative Care Research 2015;10(1):168-173
Purpose:Although ammonia shows a high due to advanced liver failure and the development of portal vein collateral circulation, there are few reports on ammonia in terminal stage of cancer. Therefore, the blood ammonia was measured against terminally ill cancer patients were studied retrospectively. Methods:For 80 cases who were admitted to the hospital for the purpose of palliative care, measured the blood ammonia at the time of admission, we have studied cancer species, gender, age, survival period, HbA1c, albumin, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, blood urea nitrogen, prothrombin activity, estimated glomerular filtration rate, C-reactive protein, hematocrit, presence or absence of liver metastases, presence or absence of opioid, laxative use, L3 level psoas major muscle area in ammonia high-value group and the normal group. Results:Hyperammonemia in terminally ill cancer patients in average survival time 41.6 days was observed in 21.3%. The significant differences in gender and liver metastasis in univariate analysis, liver metastases were extracted in the logistic regression. Conclusion:Cancer terminally ill patients with liver metastases were significantly higher to exhibit hyperammonemia in this study.
2.Risk of venous thromboembolism with a central venous catheter in hospitalized Japanese patients with inflammatory bowel disease: a propensity score-matched cohort study
Yasuhiro AOKI ; Hiroki KIYOHARA ; Yohei MIKAMI ; Kosaku NANKI ; Takaaki KAWAGUCHI ; Yusuke YOSHIMATSU ; Shinya SUGIMOTO ; Tomohisa SUJINO ; Kaoru TAKABAYASHI ; Naoki HOSOE ; Haruhiko OGATA ; Yasushi IWAO ; Takanori KANAI
Intestinal Research 2023;21(3):318-327
Background/Aims:
Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis.
Methods:
This retrospective cohort study included patients with ulcerative colitis or Crohn’s disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses.
Results:
Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn’s disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68–102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64–46.10).
Conclusions
CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.
3.Association between Osteoporosis and Skeletal Muscle Mass in Men
Masaya MIZUTANI ; Yawara EGUCHI ; Toru TOYOGUCHI ; Sumihisa ORITA ; Kazuhide INAGE ; Yasuhiro SHIGA ; Satoshi MAKI ; Junichi NAKAMURA ; Shigeo HAGIWARA ; Yasuchika AOKI ; Masahiro INOUE ; Masao KODA ; Hiroshi TAKAHASHI ; Tsutomu AKAZAWA ; Seiji OHTORI
Asian Spine Journal 2024;18(1):73-78
Methods:
This study included 99 men (mean age, 74.9 years; range, 28–93 years) who visited Qiball Clinic for BMD and body composition examinations. The osteoporosis group consisted of 24 patients (mean age, 72.5 years; range, 44–92 years), and the control group consisted of 75 individuals (mean age, 74.9 years; range, 28–93 years). Whole-body skeletal muscle mass was measured using a bioelectrical impedance analyzer. BMD was measured by dual X-ray absorptiometry. Skin autofluorescence (SAF), a marker of dermal AGE accumulation, was measured using a spectroscope. Osteoporosis was defined as a bone density T score of –2.5 or less. Physical findings, skeletal muscle mass, BMD, grip strength, and SAF were compared between the osteoporosis and control groups.
Results:
The osteoporosis group had significantly lower trunk muscle mass (23.1 kg vs. 24.9 kg), lower leg muscle mass (14.4 kg vs. 13.0 kg), and skeletal mass index (7.1 kg/m2 vs. 6.7 kg/m2) than the control group (all p<0.05). Lower limb muscle mass was identified as a risk factor for osteoporosis in men (odds ratio, 0.64; p=0.03).
Conclusions
Conservative treatment of osteoporosis in men will require an effective approach that facilitates the maintenance or strengthening of skeletal muscle mass, including exercise therapy with a focus on lower extremities and nutritional supplementation.
4.Mini-Open Anterior Retroperitoneal Lumbar Interbody Fusion: Oblique Lateral Interbody Fusion for Lumbar Spinal Degeneration Disease.
Seiji OHTORI ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Yawara EGUCHI ; Nobuyasu OCHIAI ; Shunji KISHIDA ; Kazuki KUNIYOSHI ; Yasuchika AOKI ; Junichi NAKAMURA ; Tetsuhiro ISHIKAWA ; Masayuki MIYAGI ; Hiroto KAMODA ; Miyako SUZUKI ; Gou KUBOTA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Kazuhide INAGE ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Koki ABE ; Tomoaki TOYONE ; Gen INOUE ; Kazuhisa TAKAHASHI
Yonsei Medical Journal 2015;56(4):1051-1059
PURPOSE: Surgery for lumbar spinal degeneration disease is widely performed. While posterior decompression and fusion are popular, anterior lumbar interbody fusion (ALIF) is also used for treatment. Extreme lateral interbody fusion (XLIF) is commonly used for noninvasive ALIF; however, several complications, such as spinal nerve and psoas muscle injury, have been reported. In the current study, we examined the clinical efficacy and complications of oblique lateral interbody fusion (OLIF) for lumbar spinal degeneration disease. MATERIALS AND METHODS: Thirty-five patients with degenerated spondylolisthesis, discogenic pain, and kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with or without posterior decompression, without real-time electromyography monitoring. Posterior screws were used in all patients. Visual analog scale (VAS) score and Oswestry Disability Index (ODI) were evaluated before and 6 months after surgery. Surgical complications were also evaluated. RESULTS: Pain scores significantly improved after surgery, compared to those before surgery (p<0.05). There was no patient who underwent revision surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. Few patients showed symptoms from psoas invasion. CONCLUSION: OLIF surgery produced good surgical results without any major complication.
Adult
;
Aged
;
Decompression, Surgical/*methods
;
Electromyography
;
Female
;
Humans
;
Lumbar Vertebrae/surgery
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Male
;
Middle Aged
;
Pain
;
Pain Measurement
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Scoliosis/*surgery
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Spinal Diseases/surgery
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Spinal Fusion/*methods
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Spondylolisthesis/*surgery
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Treatment Outcome
;
Young Adult
5.Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody
Takeshi SAINOH ; Takeshi SAINOH ; Sumihisa ORITA ; Sumihisa ORITA ; Masayuki MIYAGI ; Masayuki MIYAGI ; Miyako SUZUKI-NARITA ; Miyako SUZUKI-NARITA ; Yoshihiro SAKUMA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Yasuhiro OIKAWA ; Go KUBOTA ; Go KUBOTA ; Jun SATO ; Jun SATO ; Yasuhiro SHIGA ; Yasuhiro SHIGA ; Kazuki FUJIMOTO ; Kazuki FUJIMOTO ; Yawara EGUCHI ; Yawara EGUCHI ; Masao KODA ; Masao KODA ; Yasuchika AOKI ; Yasuchika AOKI ; Tsutomu AKAZAWA ; Tsutomu AKAZAWA ; Takeo FURUYA ; Takeo FURUYA ; Junichi NAKAMURA ; Junichi NAKAMURA ; Hiroshi TAKAHASHI ; Hiroshi TAKAHASHI ; Satoshi MAKI ; Satoshi MAKI ; Masahiro INOUE ; Masahiro INOUE ; Hideyuki KINOSHITA ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Masaki NORIMOTO ; Takashi SATO ; Takashi SATO ; Masashi SATO ; Masashi SATO ; Masahiro SUZUKI ; Masahiro SUZUKI ; Keigo ENOMOTO ; Keigo ENOMOTO ; Hiromitsu TAKAOKA ; Hiromitsu TAKAOKA ; Norichika MIZUKI ; Norichika MIZUKI ; Takashi HOZUMI ; Takashi HOZUMI ; Ryuto TSUCHIYA ; Ryuto TSUCHIYA ; Geundong KIM ; Geundong KIM ; Takuma OTAGIRI ; Takuma OTAGIRI ; Tomohito MUKAIHATA ; Tomohito MUKAIHATA ; Takahisa HISHIYA ; Takahisa HISHIYA ; Seiji OHTORI ; Seiji OHTORI ; Kazuhide INAGE ; Kazuhide INAGE
Asian Spine Journal 2022;16(1):99-106
Methods:
This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events.
Results:
Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events.
Conclusions
Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.
6.Mini-Open Anterior Retroperitoneal Lumbar Interbody Fusion: Oblique Lateral Interbody Fusion for Degenerated Lumbar Spinal Kyphoscoliosis.
Seiji OHTORI ; Chikato MANNOJI ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Yawara EGUCHI ; Nobuyasu OCHIAI ; Shunji KISHIDA ; Kazuki KUNIYOSHI ; Yasuchika AOKI ; Junichi NAKAMURA ; Tetsuhiro ISHIKAWA ; Masayuki MIYAGI ; Hiroto KAMODA ; Miyako SUZUKI ; Gou KUBOTA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Kazuhide INAGE ; Takeshi SAINOH ; Jun SATO ; Yasuhiro SHIGA ; Koki ABE ; Kazuki FUJIMOTO ; Hiroto KANAMOTO ; Tomoaki TOYONE ; Gen INOUE ; Kazuhisa TAKAHASHI
Asian Spine Journal 2015;9(4):565-572
STUDY DESIGN: Prospective case series. PURPOSE: To examine the clinical efficacy of mini-open anterior retroperitoneal lumbar interbody fusion: oblique lateral interbody fusion (OLIF) for degenerated lumbar spinal kyphoscoliosis. OVERVIEW OF LITERATURE: The existing surgical procedures for the treatment of spinal kyphotic deformity, including Smith-Petersen osteotomy, pedicle subtraction osteotomy, and vertebral column resection procedures, are invasive in nature. Extreme lateral interbody fusion to provide less invasive treatment of the deformity has been reported, but complications including spinal nerve and psoas muscle injury have been noted. In the current study, we examined the clinical efficacy and complications of OLIF for degenerated lumbar spinal kyphoscoliosis. METHODS: Twelve patients with degenerated lumbar spinal kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with open pedicle screws or percutaneous pedicle screws, without real-time monitoring by electromyography. Visual analog scale score and Oswestry disability index were evaluated before and 12 months after surgery, and fusion rate at OLIF cage, correction of the deformity, total blood loss, and surgical complications were also evaluated. RESULTS: Pain scores significantly improved after surgery (p<0.05). Fusion rate was found to be 90%, balance parameters also improved after surgery (p<0.05), and average total blood loss was less than 350 mL. There was no spinal nerve, major vessel, peritoneal, or urinary injury, or breakage of instrumentation. CONCLUSIONS: OLIF surgery for degenerated lumbar spinal kyphoscoliosis is less invasive than other procedures and good surgical results were produced without major complications.
Congenital Abnormalities
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Electromyography
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Humans
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Osteotomy
;
Prospective Studies
;
Psoas Muscles
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Spinal Nerves
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Spine
;
Transplants
;
Visual Analog Scale
7.Efficacy of Direct Injection of Etanercept into Knee Joints for Pain in Moderate and Severe Knee Osteoarthritis.
Seiji OHTORI ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Yawara EGUCHI ; Nobuyasu OCHIAI ; Shunji KISHIDA ; Kazuki KUNIYOSHI ; Yasuchika AOKI ; Junichi NAKAMURA ; Tetsuhiro ISHIKAWA ; Masayuki MIYAGI ; Hiroto KAMODA ; Miyako SUZUKI ; Gou KUBOTA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Kazuhide INAGE ; Takeshi SAINOH ; Jun SATO ; Yasuhiro SHIGA ; Koki ABE ; Kazuki FUJIMOTO ; Hiroto KANAMOTO ; Tomoaki TOYONE ; Gen INOUE ; Kazuhisa TAKAHASHI
Yonsei Medical Journal 2015;56(5):1379-1383
PURPOSE: Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensory nerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-alpha (TNFalpha) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFalpha inhibitor, for pain in knee OA. MATERIALS AND METHODS: Thirty-nine patients with knee OA and a 2-4 Kellgren-Lawrence grading were evaluated in this prospective study. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injection into the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. RESULTS: Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. CONCLUSION: Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFalpha is one factor that induces OA pain.
Aged
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Etanercept/*administration & dosage/therapeutic use
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Female
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Humans
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Hyaluronic Acid/administration & dosage/*therapeutic use
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Injections, Intra-Articular
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Knee Joint/physiopathology
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Male
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Middle Aged
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Neuralgia/drug therapy
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Osteoarthritis, Knee/*drug therapy
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Pain Measurement
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Prospective Studies
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Severity of Illness Index
;
Treatment Outcome
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Tumor Necrosis Factor-alpha
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Viscosupplements/administration & dosage/*therapeutic use
;
Visual Analog Scale
8.Freeze-Dried Human Platelet-Rich Plasma Retains Activation and Growth Factor Expression after an Eight-Week Preservation Period.
Yasuhiro SHIGA ; Go KUBOTA ; Sumihisa ORITA ; Kazuhide INAGE ; Hiroto KAMODA ; Masaomi YAMASHITA ; Toru ISEKI ; Michihiro ITO ; Kazuyo YAMAUCHI ; Yawara EGUCHI ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Koki ABE ; Hirohito KANAMOTO ; Masahiro INOUE ; Hideyuki KINOSHITA ; Takeo FURUYA ; Masao KODA ; Yasuchika AOKI ; Tomoaki TOYONE ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2017;11(3):329-336
STUDY DESIGN: Controlled laboratory study. PURPOSE: This study aimed to evaluate the efficacy of platelet-rich plasma (PRP) stored at room temperature (RT), frozen, or after freeze-drying. OVERVIEW OF LITERATURE: PRP enriches tissue repair and regeneration, and is a novel treatment option for musculoskeletal pathologies. However, whether biological activity is preserved during PRP storage remains uncertain. METHODS: PRP was prepared from blood of 12 healthy human volunteers (200 mL/person) and stored using three methods: PRP was stored at RT with shaking, PRP was frozen and stored at −80℃, or PRP was freeze-dried and stored at RT. Platelet counts and growth factor content were examined immediately after preparation, as well as 2, 4, and 8 weeks after storage. Platelet activation rate was quantified by flow cytometry. RESULTS: Platelet counts were impossible to determine in many RT samples after 2 weeks, but they remained at constant levels in frozen and freeze-dried samples, even after 8 weeks of storage. Flow cytometry showed approximately 80% activation of the platelets regardless of storage conditions. Almost no growth factors were detected in the RT samples after 8 weeks, while low but significant expression was detected in the frozen and freeze-dried PRP. Over time, the mean relative concentrations of various growth factors decreased significantly or disappeared in the RT group. In the frozen group, levels were maintained for 4 weeks, but decreased significantly by 8 weeks (p <0.05). The freeze-dried group maintained baseline levels of growth factors for the entire 8-week duration. CONCLUSIONS: Freeze-drying enables PRP storage while maintaining bioactivity and efficacy for extended periods.
Blood Preservation
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Flow Cytometry
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Freeze Drying
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Healthy Volunteers
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Humans*
;
Intercellular Signaling Peptides and Proteins
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Pathology
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Platelet Activation
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Platelet Count
;
Platelet-Rich Plasma*
;
Regeneration
9.Transient Receptor Potential Vanilloid 1-Immunoreactive Innervation Increases in Fractured Rat Femur.
Yuya KAWARAI ; Miyako SUZUKI ; Kensuke YOSHINO ; Gen INOUE ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Yasuchika AOKI ; Tetsuhiro ISHIKAWA ; Masayuki MIYAGI ; Hiroto KAMODA ; Go KUBOTA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Kazuhide INAGE ; Takeshi SAINOH ; Jun SATO ; Junichi NAKAMURA ; Masashi TAKASO ; Tomoaki TOYONE ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Yonsei Medical Journal 2014;55(1):185-190
PURPOSE: Pain from vertebral or femoral neck fractures is a particularly important problem in clinical orthopaedics. Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, and there are recent reports on an association between bone pain and TRPV1. However, an increase in TRPV1 activity has not been reported following femoral fracture. MATERIALS AND METHODS: We applied a neurotracer [Fluoro-gold (FG)] onto femur to detect dorsal root ganglia (DRGs) innervating the cortex of the femur in 30 Sprague Dawley rats. Seven days after application, a closed mid-diaphyseal fracture of the femur was performed. FG labeled TRPV1-immunoreactive (ir) DRGs innervating the femur were examined in nonfractured controls, and 3 days, 1 week, 2 weeks, and 4 weeks after fracture. We evaluated bone healing of the femur and compared the ratio of TRPV1-ir DRG neurons innervating the femur at the time points. RESULTS: Four weeks after fracture, complete bone union was observed. There was no significant difference in the ratio of FG labeled DRG neurons to total DRG neurons at each time point. The percentages of TRPV1-ir neurons in DRGs innervating the femur at 3 days and 1 week after fracture were significantly higher than those in control, 2 weeks, and 4 weeks after fracture (p<0.05). CONCLUSION: Fracture induced an increase of TRPV1-ir neurons in DRGs innervating the fractured femur within 3 days, and decreased during bone healing over 4 weeks. These findings show that TRPV1 may play a role in sensory sensation of bone fracture pain.
Animals
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Female
;
Femur/*innervation/*metabolism
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Immunohistochemistry
;
Rats
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Rats, Sprague-Dawley
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TRPV Cation Channels/*metabolism
10.Efficacy of Combination of Meloxicam and Pregabalin for Pain in Knee Osteoarthritis.
Seiji OHTORI ; Gen INOUE ; Sumihisa ORITA ; Masashi TAKASO ; Yawara EGUCHI ; Nobuyasu OCHIAI ; Shunji KISHIDA ; Kazuki KUNIYOSHI ; Yasuchika AOKI ; Tetsuhiro ISHIKAWA ; Masayuki MIYAGI ; Hiroto KAMODA ; Miyako SUZKUKI ; Junichi NAKAMURA ; Gou KUBOTA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Tomoaki TOYONE ; Kazuhide INAGE ; Takeshi SAINOH ; Kazuyo YAMAUCHI ; Kazuhisa TAKAHASHI
Yonsei Medical Journal 2013;54(5):1253-1258
PURPOSE: Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients. MATERIALS AND METHODS: Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test. RESULTS: Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p<0.05). No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group (p>0.05). CONCLUSION: Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.
Aged
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Aged, 80 and over
;
Drug Therapy, Combination/adverse effects
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Female
;
Humans
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Male
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Middle Aged
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Osteoarthritis, Knee/*drug therapy
;
Pain Measurement
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Thiazines/administration & dosage/adverse effects/*therapeutic use
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Thiazoles/administration & dosage/adverse effects/*therapeutic use
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gamma-Aminobutyric Acid/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use