Tommi Lamberg

Grapefruit juice substantially increases plasma concentrations of buspirone

Buspirone has a low oral bioavailability because of extensive first‐pass metabolism. The effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of orally administered buspirone is not known.

Treatment of severe spondylolisthesis in adolescence with reduction or fusion in situ: long-term clinical, radiologic, and functional outcome.

Study Design. Retrospective follow-up study with two cohorts: one treated with reduction and the other with fusion in situ. Objective. To assess the long-term effects of reduction versus fusion in situ on lumbar spine in children and adolescents with severe L5 isthmic spondylolisthesis. Summary of Background Data. Severe isthmic spondylolisthesis is commonly treated with fusion in situ, but modern surgical techniques and instrumentation permit the reduction of a severely slipped fifth lumbar vertebra. Advocates of one or another of these procedures present different claims to defend their choice. However, to our knowledge, no long-term results of the reduction maneuver exist. Methods. Between 1983 and 1991, 22 adolescents with severe (more than 60%) slip were treated surgically. In 11 of them, reduction was performed with a Magerl/Dick transpedicular device, followed by fusion posteriorly from L4 or L5 to S1 and anteriorly from L5 to S1. In the others, fusion was performed in situ posteriorly from L4 (n = 7) or L5 (n = 4) to S1 and anteriorly from L5 to S1. The average age of patients at surgery was 14.7 years (range 10.7–18.5). Radiographs obtained before surgery, after surgery, and at the final follow-up evaluation were assessed for quality of fusion. In addition, magnetic resonance imaging was obtained at the last follow-up visit. Average follow-up time was 14.8 years (range 11.6–18.7). Physical examination, spinal mobility, and nondynamometric trunk strength measurements were used to assess, and Oswestry Disability Index and Scoliosis Research Society scores were used to calculate outcome at the last follow-up visit. Results. In the reduction group, mean Oswestry Disability Index was 7.2 (range 0–20) and in the fusion in situ group, was 1.6 (range 0–4) (P = 0.0096). The Scoliosis Research Society total score averaged 90.0 (range 39–107) in the reduction group and 103.9 (range 93–120) in the fusion in situ group (P = 0.046). At the last follow-up evaluation, mean vertebral slip had decreased from the preoperative value of 90% to 57% in the reduction group but remained the same (80% vs. 78%) in the fusion in situ group (P = 0.04 and 0.013, respectively, for preoperative and postoperative comparison). On magnetic resonance imaging, disc degeneration above the fusion was more common in the reduction group (P = 0.004). None of the patients had spinal stenosis above the fusion. Nerve root canal impingement at the L5–S1 level was more common in the fusion in situ group (P = 0.03), but all patients were free of L5 nerve root symptoms. There was no difference in spinal mobility or trunk strength measurements between the groups. Conclusions. The fusion in situ group seems to perform better in almost all clinical parameters measured. These findings suggest that fusion in situ should be considered as a method of choice in severe L5 isthmic spondylolisthesis.

Operative treatment of fractures in children is increasing. A population-based study from Finland.

BACKGROUND Epidemiological data on the incidence of surgical treatment of pediatric fractures are sparse. Our aim was to determine the incidence of in-hospital-treated fractures and of the surgical treatment of these fractures in children and adolescents. METHODS National Discharge Register data on pediatric fractures (in patients younger than the age of eighteen years) treated in the hospital in Finland between 1997 and 2006 were evaluated. RESULTS During the ten-year follow-up period, the incidence (per 100,000 persons) of fractures leading to hospitalization increased by 13.5% (from 319 in 1997 to 362 in 2006; p < 0.001). This change resulted mainly from an increase in the incidence of hospital-treated upper-extremity fractures (23% increase; from 189 in 1997 to 232 in 2006). The incidence of primary fracture surgery increased by 20% (from 237 in 1997 to 284 in 2006; p < 0.001). The incidences of surgery for upper-extremity, lower-extremity, and axial fractures increased by 28%, 3.9%, and 10.7%, respectively. Within the upper-extremity-fracture group, the incremental increase was mainly due to an increase in forearm fracture surgery (62% increase; from fifty-five in 1997 to eighty-nine in 2006) (p < 0.001). CONCLUSIONS Operative treatment of childrens fractures has increased markedly during the last ten years. Evidence-based medical and economic data supporting this change in practice are sparse.

Effects of verapamil and diltiazem on the pharmacokinetics and pharmacodynamics of buspirone

Buspirone has an extensive first‐pass metabolism, which makes it potentially susceptible to drug interactions. The aim of this study was to investigate possible interactions of buspirone with verapamil and diltiazem.

Posterolateral, anterior, or circumferential fusion in situ for high-grade spondylolisthesis in young patients: a long-term evaluation using the Scoliosis Research Society questionnaire.

Study Design. A retrospective, comparative follow-up study. Objective. To compare clinical and radiographic outcomes after posterolateral, anterior, or circumferential fusion in situ for high-grade spondylolisthesis in children and adolescents. Summary of Background Data. Controversial opinions still exist about the surgical treatment of severe isthmic spondylolisthesis. There are no long-term comparative studies of different fusion in situ techniques in these patients. Methods. A total of 21 patients treated using posterolateral, 23 using anterior, and 26 using the circumferential fusion technique without instrumentation for high-grade isthmic spondylolisthesis (≥50% slip) participated. Their mean age at surgery was 14.4 years (range 8.0–19.6). The follow-up rate was 84% after a mean of 17.2 years (range 10.7–26.0). Radiographs were obtained before surgery, at 2-year follow-up, and at final follow-up. The Scoliosis Research Society (SRS) and Oswestry Disability Index questionnaires were completed, and a physical examination was performed at the final follow-up visit. Results. Progression of lumbosacral kyphosis (≥10°) was found in 9 (43%), 3 (13%), and 3 (12%) patients of the posterolateral, anterior, and circumferential fusion groups, respectively (P = 0.017). The SRS total score averaged 89.7 (range 56–105) in the posterolateral, 93.2 (range 66–114) in the anterior, and 100.0 (range 71–117) in the circumferential fusion groups (P = 0.021). Patients in the circumferential fusion group had better values for pain (P = 0.023) and function from back condition domains (P = 0.079) than patients in the posterolateral or anterior groups. The Oswestry Disability Index averaged 9.7 (range 0–62) in the posterolateral, 8.9 (range 0–32) in the anterior, and 3.0 (range 0–16) in the circumferential fusion groups (P = 0.035). Conclusions. Circumferential fusion provided significantly better long-term clinical, radiographic, and SRS total score than posterolateral or anterior fusion for high-grade isthmic spondylolisthesis.

Uninstrumented in situ fusion for high-grade childhood and adolescent isthmic spondylolisthesis: long-term outcome.

BACKGROUND Intermediate-term radiographic studies have shown that anterior and circumferential techniques result in high fusion rates in patients with high-grade spondylolisthesis, whereas posterolateral fusion is less successful. We are not aware of any long-term comparative studies in which these three methods have been evaluated with regard to functional outcome, including systematic spinal mobility and trunk strength measurements. METHODS Sixty-nine of eighty-three consecutive patients with high-grade isthmic spondylolisthesis who underwent posterolateral (twenty-one), anterior (twenty-three), or circumferential (twenty-five) uninstrumented spondylodesis between 1977 and 1991 participated in the study. The average duration of follow-up was 17.2 years. Radiographs that were made preoperatively and at the time of the most recent follow-up were assessed with regard to fusion quality and degenerative changes. Outcome was assessed at the time of the most recent follow-up by independent observers on the basis of a physical examination, spinal mobility and nondynamometric trunk strength measurements, and Oswestry Disability Index scores. RESULTS The mean preoperative vertebral slip was 61% in the posterolateral fusion group, 63% in the anterior fusion group, and 71% in the circumferential fusion group. The final fusion rate was 86% (eighteen of twenty-one) in the posterolateral fusion group, 100% (twenty-three of twenty-three) in the anterior fusion group, and 96% (twenty-four of twenty-five) in the circumferential fusion group. A decrease in lumbar intervertebral disc height at the first mobile level superior to the fusion was noted in five patients in the posterolateral fusion group, seven patients in the anterior fusion group, and one patient in the circumferential fusion group (p = 0.037). The mean Oswestry Disability Index score was 9.7 for the posterolateral fusion group, 8.9 for the anterior fusion group, and 3.0 for the circumferential fusion group (p = 0.035). Nondynamometric trunk strength measurements corresponded with referential values. Abnormally low lumbar flexion affected the posterolateral and circumferential fusion groups more often than the anterior fusion group (p = 0.0015). The percentage of slip showed inverse correlations with lumbar flexion, lumbar extension, and trunk side-bending. CONCLUSIONS As assessed on the basis of patient-based outcomes, circumferential in situ fusion provided slightly better long-term results than did posterolateral or anterior in situ fusion. When the radiographic and functional results were combined with the patient-based outcomes, the overall differences between the three groups were small.

Scoliosis research society outcome instrument in evaluation of long-term surgical results in spondylolysis and low-grade isthmic spondylolisthesis in young patients.

Study Design. A retrospective follow-up study of low-grade (slip ≤ 50%) isthmic spondylolisthesis after posterior or posterolateral fusion in young patients. Objective. To evaluate the usefulness of the Scoliosis Research Society questionnaire and compare it with Oswestry Disability Index and radiographic parameters in patients with isthmic spondylolisthesis. Summary of Background Data. A few studies have examined long-term patient outcome using validated questionnaires or compared it with radiographic parameters after surgery for isthmic spondylolisthesis in young patients. The Scoliosis Research Society questionnaire provides patient-oriented information on back pain, cosmetic aspects, patient satisfaction, and level of activity and might therefore be suitable for evaluation of surgical outcome after isthmic spondylolisthesis in young patients. However, there are no studies assessing the usefulness of the Scoliosis Research Society questionnaire for these patients. Methods. One hundred and eight patients treated at a mean (range) age of 15.9 (range, 8.1–19.8) years with posterior (n = 29) or posterolateral (n = 79) in situ fusion for isthmic spondylolisthesis participated in the present study. The follow-up rate was 83% after a mean of 20.8 (range, 15.1–25.9) years. The mean age at follow-up observation was 36.7 years. Radiographs were obtained before surgery, at 2-year follow-up observation, and at final follow-up review. The Scoliosis Research Society and Oswestry Disability Index questionnaires were completed, and a physical examination was performed at the final follow-up visit. Results. Nonunion after primary operation was found in 10 (34%) patients after posterior fusion and in 10 (13%) patients after posterolateral fusion (P = 0.0017). The mean (range) anterior slip was 25.2% (0–50%) before surgery and 24.2% (0–78%) at final follow-up observation. Lumbosacral kyphosis increased significantly during the follow-up period. The Scoliosis Research Society questionnaire yielded a total of 94.0 (range, 44–114) points. On the Scoliosis Research Society questionnaire, 14 (14%) patients reported back pain often or very often at rest. The Oswestry Disability Index scores averaged 8.2 (range, 0–68). There was a significant correlation between the Scoliosis Research Society total score and the Oswestry Disability Index. The percentage slip showed significant inverse correlations with the scores for appearance in clothes, attractiveness, and self image (Scoliosis Research Society questions 5, 14, and 15). Conclusions. Long-term clinical and radiographic outcomes after posterolateral fusion of low-grade spondylolisthesis were satisfactory. Cosmetic aspects of this deformity should be included as one of the outcome measurements, since cosmetic questions on the Scoliosis Research Society questionnaire showed inverse correlations between the amount of slip at final follow-up observation. The Scoliosis Research Society questionnaire could be used as a primary patient-oriented outcome tool after back surgery in young patients.

Long-term outcome after posterolateral, anterior, and circumferential fusion for high-grade isthmic spondylolisthesis in children and adolescents: magnetic resonance imaging findings after average of 17-year follow-up.

Study Design. A cross-sectional study to evaluate the long-term result of posterolateral (PLF), anterior (AF), and circumferential fusion (CF) for isthmic spondylolisthesis. Objectives. To assess the long-term effects of PLF, AF, or CF for high-grade isthmic spondylolisthesis on lumbar spine in children and adolescents by using MRI. Summary of Background Data. Short- and mid-term clinical and plain radiographic results of isthmic spondylolisthesis and of PLF, AF, and CF in severe slip are well documented. The long-term effect of the fusion on soft tissues, on the intervertebral discs inside and above fusion in particular, is, however, unclear. Methods. Between 1977 and 1991, PLF (n = 21), AF (n = 22), or CF (n = 24) was performed on 67 patients (42 females, 25 males) with high-grade (slip ≥50%) isthmic spondylolisthesis. The average age of patients at the time of operation was 14.4 (range, 8.9–19.6) years. Clinical, spinal mobility and trunk strength in addition to MRI and plain radiograph examinations were performed on these patients after an average follow-up time of 17.3 years (range, 10.7–26.0 years). Results. Three (14%) patients in the PLF and AF groups, but none in the CF group, reported back pain often or very often at rest. The mean Oswestry Disability Index (ODI) was 9.7 (range, 0–62) in the PLF, 8.1 (0–32) in the AF, and 2.3 (0–14) in the CF group (P < 0.05). The mean slip before surgery was 66% (range, 50%–100%) and at the last follow-up visit 66% (range, 26%–106%). Disc degeneration was most common in the PLF group (P = 0.0014) and inside the fusion and in the lowest moving intervertebral disc spaces in all subgroups. Only 1 patient had an asymptomatic prolapse. In MR images, none of the patients had lumbar central canal stenosis inside or above the fusion. In contrast, the spinal canal was wide at the spondylolysis and spondylolisthesis level in 23 (34%) patients. Of the patients, 19 (28%) patients (32 neural foramens) had severe narrowing of the neural foramen with impingement of the nerve root. No patients had clinically confirmed L5 nerve root symptoms. Muscle degeneration was found in 29 (43%) of patients. Longer fusion and muscle degeneration, but not disc degeneration, were associated with lower performance in spinal mobility and trunk-strength measurement tests. Conclusions. The clinical outcome was best in the CF group as measured by ODI. Degenerative changes were most commonly found at the level of the slip and above the fusion level. The prevalence of disc prolapses was low. Spinal fusion for isthmic spondylolysis is not associated with central canal stenosis above the fusion. Radiologic nerve root stenosis was common but asymptomatic. Mild muscle atrophy was common.

Long-term clinical, functional and radiological outcome 21 years after posterior or posterolateral fusion in childhood and adolescence isthmic spondylolisthesis

Long-term radiological studies have shown that a high rate of fusion can be achieved with posterolateral spondylodesis. Radiological findings, however, do not always correlate with patient satisfaction and outcome. No studies have been conducted on the long-term results of functional outcome, including spinal mobility and trunk strength measurements, after operative treatment of spondylolysis and spondylolisthesis, as compared with the reference population. Of 129 consecutive patients with isthmic spondylolisthesis operated on with spondylodesis between 1977 and 1987, 107 (83%) participated in the study. Posterior spondylodesis was performed in 29 (27%) patients and posterolateral spondylodesis in 78 (73%) patients. The average follow-up time was 20.9 years (range 15.1–26.2 years). Radiographs obtained preoperatively and at the 2-year and final follow-ups were assessed for quality of the fusion and degenerative changes. Outcome was assessed at the last follow-up by physical examination, spinal mobility and non-dynamometric trunk strength measurements, and calculation of Oswestry disability index (ODI) scores. The fusion rate was 66% after posterior fusion and 83% after posterolateral fusion. Degenerative changes in the lumbar intervertebral discs above the fusion level were noted in 13 (12%) patients. At the final follow-up 14% of patients reported back pain often or very often. The mean ODI score was 7.6 (0–68). Moderate disability was found in 6% of patients and severe disability in 1%; one patient was crippled. No correlation was found between disc degeneration or solidity of the fusion and the ODI score. Non-dynamometric trunk strength measurements corresponded with the reference values. Lumbar flexion, but not extension, was diminished when compared with that of the reference population. The overall long-term clinical outcome is good in patients with spondylolysis and spondylolisthesis operated on with posterior or posterolateral fusion. The clinical and radiological outcomes do not, however, appear to correlate with each other. Lumbar flexion is diminished, but the patients perform, on average, as well as the general population in non-dynamometric trunk strength measurements.

The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone

AbstractObjective: The effects of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor antidepressant, on the pharmacokinetics and pharmacodynamics of buspirone, a non-benzodiazepine anxiolytic agent, were investigated. Methods: In a randomized, placebo-controlled, two-phase cross-over study, ten healthy volunteers took either 100 mg fluvoxamine or matched placebo orally once daily for 5 days. On day 6, 10 mg buspirone was taken orally. Plasma concentrations of buspirone and its active metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), were measured up to 18 h and the pharmacodynamic effects of buspirone up to 8 h. Results: The total area under the plasma buspirone concentration-time curve was increased 2.4-fold (P < 0.05) and the peak plasma buspirone concentration 2.0-fold (P < 0.05) by fluvoxamine, compared with placebo. The half-life of buspirone was not affected. The ratio of the total area under the plasma concentration-time curve of 1-PP to that of buspirone was decreased from 7.4 [6.3 (SD)] to 4.4 (3.6) by fluvoxamine (P < 0.05). The results of the six pharmacodynamic tests remained unchanged. Conclusion: Fluvoxamine moderately increased plasma buspirone concentrations and decreased the production of the active 1-PP metabolite of buspirone. The mechanism of this interaction is probably inhibition of the CYP3A4-mediated first-pass metabolism of buspirone by fluvoxamine. However, this pharmacokinetic interaction was not associated with impairment of psychomotor performance and it is probably of limited clinical significance.