Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomized, controlled trials across a range of doses

OBJECTIVE—To evaluate the efficacy, safety, and tolerability of pregabalin across the effective dosing range, to determine differences in the efficacy of three times daily (TID) versus twice daily (BID) dosage schedules, and to use time-to-event analysis to determine the time to onset of a sustained therapeutic effect using data from seven trials of pregabalin in painful diabetic peripheral neuropathy (DPN).RESEARCH DESIGN AND METHODS—Data were pooled across seven double-blind, randomized, placebo-controlled trials using pregabalin to treat painful DPN with dosages of 150, 300, and 600 mg/day administered TID or BID. Only one trial included all three of these dosages, and TID dosing was used in four. All studies shared fundamental selection criteria, and treatment durations ranged from 5 to 13 weeks.RESULTS—Pooled analysis showed that pregabalin significantly reduced pain and pain-related sleep interference associated with DPN (150, 300, and 600 mg/day administered TID vs. placebo, all P ≤ 0.007). Only the 600 mg/day dosage showed efficacy when administered BID (P ≤ 0.001). Pain and sleep interference reductions associated with pregabalin appear to be positively correlated with dosage; the greatest effect was observed in patients treated with 600 mg/day. Kaplan-Meier analysis revealed that the median time to onset of a sustained (≥30% at end point) 1-point improvement was 4 days in patients treated with pregabalin at 600 mg/day, 5 days in patients treated with pregabalin at 300 mg/day, 13 days in patients treated with pregabalin at 150 mg/day, and 60 days in patients receiving placebo. The most common treatment-emergent adverse events were dizziness, somnolence, and peripheral edema.CONCLUSIONS—Treatment with pregabalin across its effective dosing range is associated with significant, dose-related improvement in pain in patients with DPN.The prevalence of diabetic neuropathy is as high as 50% in patients who have had diabetes for 25 years (1), and painful diabetic peripheral neuropathy (DPN) occurs in up to 26% of all people with diabetes (2). Symptoms range from mild dysesthesias to severe unremitting pain that can profoundly impact patients’ lives (3,4).Medications of several different classes are used to treat painful DPN with varying degrees of efficacy, safety, and tolerability. The antiepileptic agents gabapentin and pregabalin have attained widespread use in the treatment of painful DPN. These agents bind to the auxiliary α2-δ subunit of the voltage-sensitive calcium channel, thereby decreasing Ca²⁺ influx at nerve terminals and modulating neurotransmitter release (5).There are seven double-blind, randomized, placebo-controlled trials in painful DPN with pregabalin (6–12), five of which are published in full (7–11). The effective dosing range for treatment of neuropathic pain syndromes is 150 to 600 mg/day, administered either three times daily (TID) or twice daily (BID). Among the seven trials, dosages of 150, 300, and 600 mg/day were used, but only one trial included all three of these dosages. Thus, individually, the seven trials present an incomplete picture of the effective dosing range. In addition, TID dosing was used in the first four trials, whereas the three most recent trials of pregabalin in painful DPN used BID dosing.The objective of the current report is to use the pooled data from these seven trials to evaluate the efficacy, safety, and tolerability of pregabalin across the effective dosing range. We also use these data to determine differences in the efficacy of TID and BID dosing schedules. Finally, we use a time-to-event analysis of the pooled data to determine the time to onset of a sustained therapeutic effect across the range of doses.     

Effect of low-level laser therapy on inflammatory reactions during wound healing: comparison with meloxicam

OBJECTIVE: This study evaluated the action of low-level laser therapy (LLLT) on the modulation of inflammatory reactions during wound healing in comparison with meloxicam. BACKGROUND DATA: LLLT has been recommended for the postoperative period because of its ability to speed healing of wounds. However, data in the literature are in disagreement about its anti-inflammatory action. METHODS: Standardized circular wounds were made on the backs of 64 Wistar rats. The animals were divided into four groups according to the selected postoperative therapy: group A-control; group B-administration of meloxicam; and groups C and D-irradiation with red (lambda = 685 nm) and infrared (lambda = 830 nm) laser energy, respectively. The animals were killed at 12, 36, and 72 h and 7 days after the procedure. RESULTS: Microscopic analysis revealed significant vascular activation of irradiated sites in the first 36 h. Only group B showed decreases in the intensity of polymorphonuclear infiltrates and edema. Group D showed a higher degree of organization and maturation of collagen fibers than the other groups at 72 h. The animals in group C showed the best healing pattern at 7 days. The anti-inflammatory action of meloxicam was confirmed by the results obtained in this research. The quantification of interleukin-1beta (IL-1beta) mRNA by real-time polymerase chain reaction (PCR) did not show any reduction in the inflammatory process in the irradiated groups when compared to the other groups. CONCLUSIONS: LLLT improves the quality of histologic repair and is useful during wound healing. However, with the methods used in this study the laser energy did not minimize tissue inflammatory reactions.     

Benign neurological recovery with low recurrence and low peridural fibrosis rate in pediatric disc herniations after lumbar microdiscectomy

Lumbar disc herniation (LDH) is a very rare clinical entity in the pediatric age group, therefore only a few clinical studies have until now investigated the clinical behavior of pediatric LDH. The natural clinical history, postoperative neurological recovery with radiological follow-up and quality of life related to the disorder continue to be unknown. We prospectively planned and designed two groups of LDH patients scheduled for surgery in this study. The operations were performed by the same surgeon in a randomized fashion. The first group consisted of pediatric patients and the second group of adult patients. Both groups contained 32 cases. Postoperative neurological recovery was assessed using the visual analog scale and Aberdeen Low Back Pain Scale. Postoperative peridural fibrosis was also evaluated in postcontrast magnetic resonance sections. After 3 years of follow-up, all parameters were significantly better in the pediatric LDH group with no recurrence of the disease. The pediatric LDH group was postoperatively better than the adult group both clinically and radiologically. Although LDH seems a catastrophic disease in the pediatric age group, the clinical picture and neurological recovery have a significantly more benign course than in adult patients even in operated cases.     

Intestinal Rotation Anomalies in Childhood: Review of 22 Years’ Experience

Purpose We review our experience of treating intestinal rotation anomalies in infants and children in the 22-year period between 1978 and 2000.Methods The type of operation performed, postoperative complications, and mortality were compared in three age groups. Group 1 consisted of neonates 1 month old, Group 2 consisted of infants aged 1 year old, and Group 3 consisted of children aged 1 year old.Results There were 101 infants and children, with a female:male ratio of 2:1. Of the 101 patients, 72 (71%) were neonates, with a mean age of 11.8 days (range 1–28 days); 20 (19.8%) were under the age of 1 year, with a mean age of 6.7 months (range 1–12 months); and 9 (8.9%) were 1 year of age, with a mean age of 6 years (range 1–9 years). Eighty-five (84%) patients underwent emergency procedures. Ladds operation was performed in all patients, with various additional procedures. The most frequent postoperative complications were adhesive intestinal obstruction, stoma necrosis, evisceration, and short bowel syndrome. The mortality rate was 36% in Group 1, 20% in Group 2, and 0% in Group 3.Conclusions In this series surgery was usually performed as an emergency procedure, with higher morbidity and mortality in newborns than in older infants and children.     

Psoas abscess as a complication of pyogenic sacroiliitis: report of a case

A psoas abscess is, either primary or secondary, a rare entity for a general surgeon. Images by ultrasonography and computed tomography (CT) can help a general surgeon to make an accurate diagnosis when encountering the patient complaining of unilateral lower abdominal deep pain with fever. A case of pyogenic abscess of the psoas muscle as a result of sacroiliitis in a 22-year-old man is reported herein. The abdominal CT and magnetic resonance imaging scans demonstrated a large multilocular abscess extending along the iliopsoas muscle, and erosion and a widening of the left sacroiliac joint. The abscess was drained with an open surgical approach and the patient responded well to antibiotic therapy. Aggressive surgical and medical treatment is necessary in patients with psoas abscess to prevent complications. Received: March 5, 2001 / Accepted: November 20, 2001     

Ovary-sparing surgery for teratomas in children

Aim

To share our experience in ovary-sparing surgery for teratomas in children.

Patients and methods

The medical records of nine patients (mean age of 11.2 years, r 6–15 years) who had undergone ovary-sparing surgery for teratoma were analyzed retrospectively. Mean duration for follow-up was 29.5 months (r 15–75 months).

Results

Five patients suffered from chronic abdominal pain; two had acute colicky abdominal pain. In two patients, there was no presenting clinical symptom. Two patients were operated on emergency basis due to symptoms related with acute abdomen. On the other hand, seven were operated electively. Ultrasonography was performed in all patients. Additionally, MRI and tumor markers were performed in all but two. Main radiologic findings consisted of heterogenous cystic and solid ovarian masses predictive of teratoma. The definitive diagnosis in emergency cases were as follows: perforated appendicitis plus teratoma [1]; torsion of the ovarian mass with teratoma [1]. The final diagnosis in electively treated seven patients were: unilateral ovarian teratoma [4], bilateral ovarian teratoma [1], bilateral teratoma plus appendiceal inflammatory mass [1], unilateral teratoma and contralateral corpus hemorrhagicum cyst [1]. The operations were performed by open conventional surgery in six and laparoscopy in three patients. The procedures were ovary-sparing surgery in 12 ovaries, appendectomy in 2 patients and detorsion of ovary in 1 patient. The main indication for ovary-sparing surgery was the “existence of a perfect dissection plane between the tumor margins and healthy ovarian tissue”. The remaining ovarian tissue was evaluated macroscopically for residual lesions. Frozen section was performed in three suspected patients and the ovarian margins were free of any tumor cell. The pathologic diagnosis was: mature cystic teratoma in 10, immature teratoma in 1 and corpus hemorrhagicum cyst in 1. The postoperative outcome and follow-up was uneventful.

Conclusion

Heterogenous ovary mass containing solid and cystic portions with echogenic areas on ultrasound imaging is highly suggestive of ovarian teratomas. Emergent surgical intervention is indicated if there is any suspicion of ovarian torsion. Otherwise, MRI is performed for further radiological evaluation. Based on radiologic findings, ovary-sparing surgery can be safely performed if the preoperative diagnosis is teratoma and there is always a plane of dissection between the normal ovary and cyst wall.     

Coexistence of Hodgkin lymphoma and cyst hydatic disease of the liver

Although both Hodgkin lymphoma and cyst hydatic disease in children have been seen with an increased frequency, there is no previously reported case of Hodgkin lymphoma associated with cyst hydatic disease from Turkey. The authors report such a case of Hodgkin lymphoma. Intrahepatic cystic masses were diagnosed during ultrasound examination for clinical staging on admission. The diagnosis of cyst hydatic of the liver was confirmed by surgery. Although there was no residual and/or new cyst formation on radiologic follow-up, elevated antibody titers (indirect hemagglutination test) persisted following surgical excision at least for 2 years of follow-up.