Demographics and medical burden of osteogenesis imperfecta: a nationwide database analysis.

The epidemiological data on osteogenesis imperfecta (OI) in Asia is limited. This study, representing the first comprehensive epidemiological investigation on OI in Taiwan, reveals high medical resource utilization and underscores the importance of early diagnosis to enhance care quality. INTRODUCTION: This study examines osteogenesis imperfecta, a hereditary connective tissue disorder causing pediatric fractures and limb deformities, using a nationwide database from Taiwan to analyze clinical features and medical burden. METHODS: The study identified validated OI patients from the Catastrophic Illness Registry in the National Health Insurance Research Database from 2008 to 2019. Demographic data and medical resource utilization were analyzed. A multivariate Cox model assessed the influence of sex, validation age, and comorbidities. RESULTS: 319 OI patients (M/F = 153/166) were identified, with 58% validated before age 20. Prevalence and incidence were 0.8-1.3/100,000 and 0.02-0.09/100,000, respectively, with higher rates in the pediatric demographic. In the study period, 69.6% of the patients had admission history, primarily to pediatric and orthopedic wards. The median admission number was 3, with a median length of stay of 12 days and a median inpatient cost of approximately 3,163 USD during the period. Lower limb fractures were the main reason for hospitalization. 57% of OI patients received bisphosphonate treatment. The leading causes of mortality were OI-related deaths, neurovascular disease, and cardiovascular disease. The median age of validation in the non-survival group was significantly higher compared to the survival group (33 vs. 14 years), and patients validated during childhood required more inpatient fracture surgeries than those validated during adulthood. CONCLUSION: This study provides comprehensive real-world evidence on the clinical characteristics and high medical resource utilization of OI patients in a low prevalence region like Taiwan. Early diagnosis is crucial for improving care quality and enhancing health outcomes.

Non-Surgical Strategies for Managing Skeletal Deformities in a Child with X-Linked Hereditary Hypophosphatemic Ricket: Insights and Perspectives.

This case report sheds light on the management of skeletal deformity in a young child with X-linked hypophosphatemia (XLH), emphasizing the significance of a timely orthotic intervention alongside pharmacological treatment, which is a strategy not frequently highlighted in the XLH literature. The patient, a 2-year-and-7-month-old female, presented with classic XLH symptoms, including short stature, pronounced genu varum, and hypophosphatemia, with deformities observed in both the coronal and sagittal planes of the femur and tibia. Despite initial reliance on pharmacotherapy, which proved insufficient for skeletal realignment, the integration of orthotic treatment at age 3 marked a pivotal turn in the management strategy. By the age of 5 years and 9 months, this combined approach yielded significant improvements: the deformities in the femur and tibia were notably corrected, tibial torsion was addressed, and enhanced limb alignment was achieved, as corroborated by radiographic evidence. This case underscores the effectiveness of orthotic intervention as a critical and underemphasized adjunct to pharmacological therapy in managing XLH in early childhood. It advocates for the early inclusion of orthotic measures to optimize treatment outcomes and expand the range of management strategies for limb deformities.

The use of ultrasound for monitoring reduction and ulnar nerve subluxation in pediatric humeral supracondylar fractures.

BACKGROUND: Traditional treatment for displaced humeral supracondylar fractures (SCFs) in children involves closed reduction (CR) under fluoroscopic guidance, percutaneous pinning, and immobilization with a long-arm cast. This study aims to explore the viability of using radiation-free ultrasound (US) for guiding CR and tracking ulnar nerve dynamics during medial pinning, contrasting the US method with the conventional cross pinning technique. MATERIALS AND METHODS: We assessed 70 children with acute displaced SCFs. The US group (n = 30) underwent US-guided reduction, whereas the traditional group (n = 40) underwent fluoroscopy-guided reduction. Both groups received percutaneous cross pinning and subsequent cast immobilization. Postoperative outcomes were compared between the two methods after a 6-month follow-up. In the US group, ultrasonography assessed fracture displacement distances before and after CR. The angle at which the ulnar nerve relocated to the cubital tunnel during elbow extension was documented using real-time US monitoring during medial pinning. RESULTS: The US group demonstrated improved reduction accuracy, increased range of motion, superior restoration of both Baumann and Humeroulnar angles, and a decreased incidence of malunions compared to the traditional group (all p < 0.05). The ultrasonographic measurement of fracture displacement was comparable with that of fluoroscopy (intraclass correlation coefficient > 0.90). In the US group, no ulnar nerve injury was noted, compared to 2.5 % in the traditional group, and real-time US observations revealed ulnar nerve hypermobility, with 53.3 % of patients exhibiting anterior ulnar nerve subluxation at 120° elbow flexion, 40 % at 90°, 16.7 % at 60°, and none at 30° flexion. CONCLUSION: Ultrasound is as reliable as fluoroscopy for evaluating fracture reductions. The use of intra-operative ultrasound significantly improves reduction accuracy and radiographic outcomes while reducing the risk of ulnar nerve injury.

Determining the Optimal Treatment for Idiopathic Clubfoot: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clubfoot, or congenital talipes equinovarus deformity, is a common anomaly affecting the foot in infants. However, clinical equipoise remains between different interventions, especially those based on the Ponseti method. The aim of this study was to examine the clinical outcomes of the various interventions for treating idiopathic clubfoot. METHODS: Searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Scopus, and CINAHL were conducted. Randomized controlled trials comparing different interventions, including the Ponseti method, accelerated Ponseti method, Ponseti method with botulinum toxin type A (Botox) injection, Ponseti method with early tibialis anterior tendon transfer (TATT), Kite method, and surgical treatment, were included. Network meta-analyses (NMAs) were conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) reporting guidelines. The primary outcomes were the change in total Pirani score and maximal ankle dorsiflexion. Secondary outcomes were the number of casts, time in casts, and rates of tenotomy, total complications, relapse, adverse events, and additional required major surgery. RESULTS: Eleven randomized controlled trials involving 740 feet were included. According to the SUCRA (surface under the cumulative ranking curve)-based relative ranking, the Ponseti method was associated with the best outcomes in terms of Pirani score changes, maximal ankle dorsiflexion, number of casts, adverse events, and total complications, whereas the accelerated Ponseti method was associated with the best outcomes in terms of time in casts and tenotomy rate. Early TATT ranked best in terms of relapse rate. The Ponseti method with Botox injection was associated with the best outcomes in terms of the need for additional major surgery. CONCLUSIONS: The NMAs suggest that the Ponseti method is the optimal treatment overall, despite potential drawbacks such as longer time in casts and higher rates of tenotomy, relapse, and the need for additional surgery compared with other modified approaches. Therefore, clinicians should consider how treatments can be tailored individually. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Is implant choice associated with fixation strength for displaced radial neck fracture: a network meta-analysis of biomechanical studies.

The multitude of fixation options for radial neck fractures, such as pins, screws, biodegradable pins and screws, locking plates, and blade plates, has led to a lack of consensus on the optimal implant choice and associated biomechanical properties. This study aims to evaluate the biomechanical strength of various fixation constructs in axial, sagittal, and torsional loading directions. We included biomechanical studies comparing different interventions, such as cross/parallel screws, nonlocking plates with or without augmented screws, fixed angle devices (T or anatomic locking plates or blade plates), and cross pins. A systematic search of MEDLINE (Ovid), Embase, Scopus, and CINAHL EBSCO databases was conducted on September 26th, 2022. Data extraction was carried out by one author and verified by another. A network meta-analysis (NMA) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Primary outcomes encompassed axial, bending, and torsional stiffness, while the secondary outcome was bending load to failure. Effect sizes were calculated for continuous outcomes, and relative treatment ranking was measured using the surface under the cumulative ranking curve (SUCRA). Our analysis encompassed eight studies, incorporating 172 specimens. The findings indicated that fixed angle constructs, specifically the anatomic locking plate, demonstrated superior axial stiffness (mean difference [MD]: 23.59 N/mm; 95% CI 8.12-39.06) in comparison to the cross screw. Additionally, the blade plate construct excelled in bending stiffness (MD: 32.37 N/mm; 95% CI - 47.37 to 112.11) relative to the cross screw construct, while the cross-screw construct proved to be the most robust in terms of bending load failure. The parallel screw construct performed optimally in torsional stiffness (MD: 139.39 Nm/degree; 95% CI 0.79-277.98) when compared to the cross screw construct. Lastly, the nonlocking plate, locking T plate, and cross-pin constructs were found to be inferior in most respects to alternative interventions. The NMA indicated that fixed angle devices (blade plate and anatomic locking plate) and screw fixations may exhibit enhanced biomechanical strength in axial and bending directions, whereas cross screws demonstrated reduced torsional stability in comparison to parallel screws. It is imperative for clinicians to consider the application of these findings in constraining forces across various directions during early range of motion exercises, taking into account the distinct biomechanical properties of the respective implants.

Young Children with a Bucket-Handle Tear to the Discoid Lateral Meniscus Successfully Treated Using Arthroscopic Saucerization and Repair: Two Case Reports.

Observations of a symptomatic discoid lateral meniscus in young children are infrequent. The objective of this report was to demonstrate the use of arthroscopic saucerization and repair for treating a bucket-handle tear of a lateral discoid meniscus in two young children. Two young children (a 28-month-old girl and a 5-year-old boy) presented with a bucket-handle tear of the complete type lateral discoid meniscus. Both patients received arthroscopic saucerization and repair. A full knee extension under a long leg cast was applied for one month after surgery. The two patients were able to achieve a full range of motion of their operated knees without limping or presenting an antalgic gait at the third month after surgery. Both patients and their parents felt satisfied with the treatment at the 2- and 3-year follow-ups, respectively. Our results demonstrated that arthroscopic saucerization and repair seems to be an effective treatment for bucket-handle tears of the lateral discoid meniscus in young children-even those younger than 3 years old. We reported the youngest case (a 28-month-old girl) in comparison with the findings from a literature review.

The reimbursement coverage decisions and pricing rules for medical devices in Taiwan.

Medical technology is undergoing rapid transformations, and the classifications of medical devices have also expanded greatly; therefore, it is necessary to develop appropriate reimbursement policies and pricing mechanisms in a timely manner. This paper aims to introduce the reimbursement coverage and pricing rules for medical devices in Taiwan. In addition, this paper identifies and evaluates available health technology assessments (HTA) and literature on published websites concerning medical device decision-making processes and pricing systems in South Korea and Japan, which are near Taiwan and have similar reimbursement coverage processes. Reimbursement policy and pricing mechanisms are constantly being revised in Taiwan, Japan, and South Korea. Recently, all three countries attempted to establish new reimbursement coverage decision-making and pricing rules, adopting a differentiated approach based on the level of evidence required for the appropriated reimbursement in terms of a feasible evaluation mechanism for providing patients with more effective medical devices. This article is expected to contribute to providing references to new reimbursement coverage decision-making and pricing rules.

Impact of disease-specific care certification on clinical outcome and healthcare performance of myocardial infarction in Taiwan.

BACKGROUND: The relationship between certification for specific disease care and clinical outcome was not well known. Previous studies regarding the effect of certification for acute stroke centers were limited by their cross-sectional design. This study aimed to investigate the effect of disease-specific care (DSC) certification on healthcare performance and clinical outcome of acute myocardial infarction (AMI). METHODS: This retrospective, longitudinal, controlled study was performed by analyzing the nationwide Taiwan Clinical Performance Indicators dataset from 2011 to 2018. Hospitals undergoing DSC certification for coronary care and reporting AMI indicators 1 year before, during, and 1 year after certification were included in group C, whereas hospitals not seeking DSC certification but reporting AMI indicators during the same period were included in group U. The primary endpoint was in-hospital mortality of AMI. RESULTS: In total, 20 hospitals (9 in group C and 11 in group U) and up to 16 173 AMI cases were included for analysis. In-hospital mortality was similar between both groups at baseline. However, the in-hospital mortality was significantly improved during and after certification periods in comparison with that at baseline in group C (6.8% vs 8.4%, p = 0.04; 6.7% vs 8.4%, p = 0.02), whereas there was no significant change in group U, resulting in a statistically significant difference between both groups during and after certification periods (odds ratio = 0.74 [95% CI = 0.60-0.91] and 0.78 [95% CI = 0.64-0.96]). Compared with group U, the improvement in healthcare performance indicators, such as door-to-electrocardiography time <10 minutes, blood testing for low-density lipoprotein cholesterol level, prescribing a beta-blockade or a P2Y12 receptor inhibitor during hospitalization, prescribing a statin on discharge, and consultation for cardiac rehabilitation, was significant in group C. CONCLUSION: The current study demonstrated the beneficial effect of DSC certification on clinical outcome of AMI probably mediated through quality improvement during the healthcare process.

Tension wiring to increase stability of conventional plating for proximal humeral fractures: An alternative to a locking plate.

Fixation of comminuted or osteoporotic fractures in the proximal humerus is a challenge for orthopedic surgeons. In the past two decades, locking plates have been used for proximal humeral fracture fixation. However, complications such as loss of reduction have been reported, and the implants are not always available in some regions. Therefore, we describe an alternative procedure involving fixation with a nonlocking cloverleaf plate augmented with tension wiring to provide adequate stability and prevent loss of reduction.

Fracture risk and correlating factors of a pediatric population with attention deficit hyperactivity disorder: a nationwide matched study.

The aim of this study was to investigate the risk of fracture and the difference between sexes from a nationwide database of fracture risk among children aged 4-17 years with or without attention deficit hyperactivity disorder (ADHD, ICD-9-CD codes 314). The Longitudinal Health Insurance Database (LHID 2000) was used to analyze fracture characteristics of children from the National Health Insurance that covered 96.1% of the Taiwanese population (N=21.4 million). A total of 7200 ADHD children aged between 4 and 17 years whose diagnosis had been confirmed in at least three outpatient clinics between 1 January 2000 and 31 December 2009 were included, and a cohort of 36 000 children without ADHD matched for age, sex, and urbanization was recruited for analysis. The incidence rate of fractures in ADHD children was 21.0 (95% confidence interval=19.4-22.7) per 1000 person-years, significantly (P<0.001) higher than 15.0 (95% confidence interval=14.4-15.6) in non-ADHDs. After adjusting by age, sex, urbanization level, and geographic region, the statistically significant (P<0.001) hazard ratios (HR) of fracture for ADHD children compared with non-ADHD children included 1.62 in girls and 1.38 in boys, 1.53 in the skull, neck, and trunk (ICD-9-CM 800-809), 1.28 in the upper extremity (ICD-9-CM 810-819), and 1.84 in the lower extremity (ICD-9-CM 820-829). The HR also (P<0.001) increased significantly in all age groups, including 1.35 in 4-6, 1.37 in 7-9, and 1.54 in 10-17 years. ADHD should be listed among risk factors of children's fractures in each sex, all age groups, and all body areas that the parents, teachers, caregivers of ADHD children, and pediatric orthopedists should be aware of. Besides, ADHD girls were more affected than ADHD boys, especially after 10 years of age, whereas the adjusted HR was the highest in the lower extremities. Nationwide analysis matched for age and sex showed that ADHD should be considered the risk factor of children's fracture, especially for girls older than 10 years of age.

The dangers of hemilithotomy positioning on traction tables: case report of a well-leg drop foot after contralateral femoral nailing.

BACKGROUND: Postoperative contralateral morbidities after fracture fixation surgery by hemilithotomy positioning on traction table is uncommon. We'd report a case of unexpected common peroneal nerve palsy developed on the contralateral side manifesting with drop foot after a common orthopedic femoral nailing. CASE REPORT: A 28-year-old female sustained an unusual common peroneal nerve palsy manifesting contralateral drop foot after prolonged femoral nailing. Although the initial presentations were similar to the notorious well-leg compartment syndrome, a benign course with complete recovery in functions was observed 3 months later. After neurophysiologic exam and review of pertinent literature, this iatrogenic and transient dysfunction was delineated to be position-related neuropraxia. CONCLUSION: Position adjustment at intervals or complete avoidance of prolonged knee hyperflexion is recommended to prevent contralateral common peroneal nerve morbidity.

Effect of shoulder abduction on the fixation of humeral greater tuberosity fractures: a biomechanical study for three types of fixation constructs.

BACKGROUND: An abduction brace and abduction exercises are commonly employed after humeral greater tuberosity fracture repair. However, the effects of glenohumeral abduction on the biomechanical strength have seldom been elucidated. METHOD: We studied 24 pairs of female fresh frozen porcine shoulders randomly divided into 3 groups. After creation of a greater tuberosity fracture on each shoulder, 3 fixation techniques were used for the 3 groups: double-row suture anchor fixation (DR), suture bridge technique (SB), and 2-screw fixation (TS). This biomechanical study was conducted to compare the forces that create 3- and 5-mm displacements and the ultimate failure load at the simulated shoulder abduction angles of 0° and 45° among the 3 groups. RESULTS: In the DR group, the mean forces to create 3- and 5-mm displacements and the failure load at 0° were higher than those at 45° (P = .036, P = .012, P = .027). By contrast, in the SB group, the mean forces to create 3- and 5-mm displacements at 45° were greater than those at 0° (P = .012, P = .012). There were no significant differences in the forces to create 3- and 5-mm displacements and construct failure between 0° and 45° in the TS group (P = .575, .327, .478). CONCLUSION: The DR group had greatest initial fixation strength at a low abduction angle, whereas the SB group had the highest initial fixation strength at a high abduction angle. The TS group appeared unaffected by the abduction angle.

Adjacent disc and facet joint degeneration in young adults with low-grade spondylolytic spondylolisthesis: A magnetic resonance imaging study.

BACKGROUND/PURPOSE: Premature adjacent-level degeneration has been attributed to vertebral fusion, but spondylolisthesis has not been reported as a pathological factor responsible for the degeneration of adjacent disc and facet joint. We hypothesized that the degeneration of disc and facet joints in the adjacent levels is correlated with spondylolisthesis. METHODS: Magnetic resonance images of 35 symptomatic young adults (16-29 years old) with low-grade L5-S1 spondylolytic spondylolisthesis (Meyerding Grade 1 or 2) and 50 symptomatic young referents (20-29 years old) with L5-S1 disc herniation without spondylolisthesis were recruited to compare the differences between disc and facet-joint degenerations at the olisthetic and adjacent levels using the Mantel extension test. RESULTS: There were statistically significant degenerative changes of the discs and facet joints at the olisthetic and adjacent levels of patients with spondylolytic spondylolisthesis compared with the reference group. There is a trend that the disc and facet joints degenerate the most at the olisthetic level and become less affected at adjacent levels away from the lesion of pars defect. CONCLUSION: Low-grade spondylolytic spondylolisthesis was associated with significant degenerations of the disc and facet joints at olisthetic and adjacent levels in young adults.

Shielding during x-ray examination of pediatric female patients with developmental dysplasia of the hip.

Patients with developmental dysplasia of the hip (DDH) generally undergo multiple x-ray examinations of both hip joints. During these examinations, the gonads are completely exposed to radiation, unless shielded. Although many types and sizes of gonad shields exist, they often do not provide adequate protection because of size and placement issues; additionally, these shields are frequently omitted for female patients. Our aim was to assess gonad protection during x-ray examination that is provided by gonad shields designed for individual female patients with DDH.We retrospectively retrieved data from the Picture Archiving and Communication System database; pelvic plain x-ray films from 766 females, 18 years old or younger, were included in our analysis. Based on x-ray measurements of the anterior superior iliac spine, we developed a system of gonad shield design that depended on the distance between anterior superior iliac spine markers. We custom-made shields and then examined shielding rates and shielding accuracy before and after these new shields became available. Standard (general-purpose) shields were used before our custom design project was implemented. The shielding rate and shielding accuracy were, respectively, 14.5% and 8.4% before the project was implemented and 72.7% and 32.2% after it was implemented. A shield that is more anatomically correct and available in several different sizes may increase the likelihood of gonad protection during pelvic x-ray examinations.

The severity of the long head biceps tendinopathy in patients with chronic rotator cuff tears: macroscopic versus microscopic results.

BACKGROUND: This study investigated the histopathology of the long head of biceps (LHB) tendon and correlated the findings with the macroscopic appearances of the LHB and the size of rotator cuff tears (RCTs) in patients with chronic RCTs. METHODS: We compared biopsy specimens from LHBs in 34 patients with chronic RCTs and grossly normal LHBs in 8 patients undergoing shoulder hemiarthroplasty (controls). Duration of preoperative symptoms, the severity of RCTs, and macroscopic appearance of LHBs were recorded, classified, and compared with the histologic grading and apoptosis index of terminal deoxynucleotide transferase-mediated biotin-deoxy uridine triphosphate nick-end labeling (TUNEL) assays of LHBs. RESULTS: In the RCT group, there were 8 partial-thickness tears with 5 macroscopic LHB lesions, 12 full-thickness tears with 8 macroscopic LHB lesions, and 14 massive tears with 13 macroscopic LHB lesions. There were 6 LHB subluxations. However, the macroscopic grading and the symptom duration were not correlated with the severity of the histology. In patients with massive tears, no matter what the macroscopic appearance of the LHB, the proportion of end-stage (grade 4) histologic LHB tendinopathy significantly increased (85.7%, P < .05) compared with patients with other types of RCTs. There was a consistently high incidence of advanced LHB histology (grade 3 or higher) in each classification of RCTs (75.0%-100.0%). The 8 patients in the control group showed milder histopathology (grade 1 or 2). The apoptosis index significantly increased as the tendinopathy progressed (P < .05). CONCLUSIONS: The macroscopic pathology of LHB may not fully reflect the severity of tendinopathy, and the coexisting size of RCTs plays a role in the severity of LHB tendinopathy.

Arthroscopically assisted percutaneous fixation of displaced midclavicular fracture using a Knowles pin.

Clavicle fractures are common traumatic injuries of the shoulder girdle, with surgery being the recommended treatment for some displaced midshaft fractures. Open surgery is widely used; however, the primary concerns of this procedure include cosmetic problems and incisional complications, such as wound dehiscence, infection, numbness, and sensitivity. A new arthroscopically assisted technique was developed, in which the Knowles pin was used for percutaneous fixation to treat the displaced midclavicular fracture. This technique is an attractive alternative treatment option for midclavicular fractures.

Mesh Achilles tendon lengthening--a new method to treat equinus deformity in patients with spastic cerebral palsy: surgical technique and early results.

Equinus of the ankle is a common deformity in spastic cerebral palsy. Many methods have been developed to lengthen the Achilles tendon to correct the deformity. A new mesh Achilles tendon lengthening (ATL) procedure that might decrease immobilization and promote recovery was performed in 36 tendons with equinus deformity (22 patients, average age=6.2). The results were compared with those of two other methods: the Vulpius group and the Z-lengthening group. The corrected dorsiflexion angle of the ankle at a subsequent 2-year follow-up of the mesh ATL and Vulpius groups matched (25.5±3.0 and 27.1±3.5°, respectively), whereas that of the Z-lengthening group was higher (33.9±3.8°). Nevertheless, statistics of the timing of each patient's readiness to begin rehabilitation and walking as well as gaining better stability for running and one-legged hopping indicated that the mesh ATL group recovered significantly quicker than the Vulpius and Z-lengthening groups. The mesh ATL procedure achieves a successful correction of the equinus deformity in spastic cerebral palsy comparable with that of the Vulpius procedure, with the advantage of preserving the gastrocnemius without a complete section. This confers greater antigravity stability and quicker recovery in patients.

An open label trial of the effects and safety profile of extended-release tramadol in the management of chronic pain.

OBJECTIVES: Tramadol is a synthetic centrally-acting opioid analgesic. The newly developed extended-release formulation of tramadol offers a more stable plasma concentration and could improve patients' compliance. The purpose of this study was to evaluate the efficacy, safety, and adverse events of extended release tramadol in Taiwanese patients with moderate to severe chronic noncancer pain. METHODS: Sixty-six patients with moderate to severe chronic noncancer pain previously treated with conventional tramadol but unsatisfied with its efficacy were enrolled from four medical centers. The patients received the extended-release tramadol once daily for a week. RESULTS: The usage of extended-release tramadol was more efficacious as the patients' visual analog scale score dropped significantly (-16 ± 14.1). In this study, the reported adverse events were similar to those of previous studies. Thirty patients reported adverse events and one patient reported a serious adverse event but was justified unrelated to the study drug. The most common adverse event was dizziness, followed by vomiting, nausea, somnolence, and constipation in sequence. In this study, patients with dizziness were observed to have a lower initial pain score (p = 0.032). Furthermore, the rate of premature termination and dizziness was closely correlated (p = 0.027). CONCLUSION: Patients with chronic pain could obtain significantly better pain relief after the switch to larger doses of extended-release tramadol with safety and without severe adverse effects in a short period of time. Less severe adverse effects (no life-threatening event) was the leading cause of premature termination.