Abstracts 2013

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Progressively increasing fracture risk with advancing age after initial incident fragility fracture: The Tromsø Study

The risk of subsequent fracture is increased after initial fractures; however, proper understanding of its magnitude is lacking. This population‐based study examines the subsequent fracture risk in women and men by age and type of initial incident fracture. All incident nonvertebral fractures between 1994 and 2009 were registered in 27,158 participants in the Tromsø Study, Norway. The analysis included 3108 subjects with an initial incident fracture after the age of 49 years. Subsequent fracture (n = 664) risk was expressed as rate ratios (RR) and absolute proportions irrespective of death. The rates of both initial and subsequent fractures increased with age, the latter with the steepest curve. Compared with initial incident fracture rate of 30.8 per 1000 in women and 12.9 per 1000 in men, the overall age‐adjusted RR of subsequent fracture was 1.3 (95% CI, 1.2–1.5) in women, and 2.0 (95% CI, 1.6–2.4) in men. Although the RRs decreased with age, the absolute proportions of those with initial fracture who suffered a subsequent fracture increased with age; from 9% to 30% in women and from 10% to 26% in men, between the age groups 50–59 to 80+ years. The type of subsequent fracture varied by age from mostly minor fractures in the youngest to hip or other major fractures in the oldest age groups, irrespective of type and severity of initial fracture. In women and men, 45% and 38% of the subsequent hip or other major fractures, respectively, were preceded by initial minor fractures. The risk of subsequent fracture is high in all age groups. At older age, severe subsequent fracture types follow both clinically severe and minor initial incident fractures. Any fragility fracture in the elderly reflects the need for specific osteoporosis management to reduce further fracture risk. © 2013 American Society for Bone and Mineral Research.     

National Estimates of Exposure to Traumatic Events and PTSD Prevalence Using DSM‐IV and DSM‐5 Criteria

Prevalence of posttraumatic stress disorder (PTSD) defined according to the American Psychiatric Association's Diagnostic and Statistical Manual fifth edition (DSM‐5; 2013) and fourth edition (DSM‐IV; 1994) was compared in a national sample of U.S. adults (N = 2,953) recruited from an online panel. Exposure to traumatic events, PTSD symptoms, and functional impairment were assessed online using a highly structured, self‐administered survey. Traumatic event exposure using DSM‐5 criteria was high (89.7%), and exposure to multiple traumatic event types was the norm. PTSD caseness was determined using Same Event (i.e., all symptom criteria met to the same event type) and Composite Event (i.e., symptom criteria met to a combination of event types) definitions. Lifetime, past‐12‐month, and past 6‐month PTSD prevalence using the Same Event definition for DSM‐5 was 8.3%, 4.7%, and 3.8% respectively. All 6 DSM‐5 prevalence estimates were slightly lower than their DSM‐IV counterparts, although only 2 of these differences were statistically significant. DSM‐5 PTSD prevalence was higher among women than among men, and prevalence increased with greater traumatic event exposure. Major reasons individuals met DSM‐IV criteria, but not DSM‐5 criteria were the exclusion of nonaccidental, nonviolent deaths from Criterion A, and the new requirement of at least 1 active avoidance symptom.     

Inclusion of CYP3A5 genotyping in a nonparametric population model improves dosing of tacrolimus early after transplantation

Following organ engraftment, initial dosing of tacrolimus is based on recipient weight and adjusted by measured C₀ concentrations. The bioavailability and elimination of tacrolimus are affected by the patients CYP3A5 genotype. Prospective data of the clinical advantage of knowing patient's CYP3A5 genotype prior to transplantation are lacking. A nonparametric population model was developed for tacrolimus in renal transplant recipients. Data from 99 patients were used for model development and validation. A three‐compartment model with first‐order absorption and lag time from the dosing compartment described the data well. Clearances and volumes of distribution were allometrically scaled to body size. The final model included fat‐free mass, body mass index, hematocrit, time after transplantation, and CYP3A5 genotype as covariates. The bias and imprecision were 0.35 and 1.38, respectively, in the external data set. Patients with functional CYP3A5 had 26% higher clearance and 37% lower bioavailability. Knowledge of CYP3A5 genotype provided an initial advantage, but only until 3‐4 tacrolimus concentrations were known. After this, a model without CYP3A5 genotype predicted just as well. The present models seem applicable for clinical individual dose predictions but need a prospective evaluation.     

Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome

Background

Rituximab (RTX) has recently showed promising results in the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS).

Methods

This was a retrospective multicenter study of 18 children treated with RTX for SDNS, with a mean follow-up of 3.2 years. RTX was introduced because of side effects or relapses during therapy with immunosuppressive agents. The children received one to four infusions of RTX during the first course of treatment, and subsequent infusions were given due to CD19-cell recovery (CD19?>1 %; 54 % of children) or relapse (41 %), as well as systematically (5 %).

Results

Treatment with RTX maintained sustained remission without relapse in 22 % of patients and increased the duration of remission in all other patients. The time between two successive relapses was 9 months in the absence of re-treatment and 24.5 months when infusions were performed at the time of CD19-cell recovery. At the last follow-up, 44.5 % of patients were free of oral drug therapy. Of those still receiving oral drugs, all doses had been decreased. No serious adverse events occurred.

Conclusion

The results of this retrospective study confirm the efficacy and very good safety of RTX in the treatment of SDNS. The optimal therapeutic protocol seems to be a repeated single infusion at the time of CD19-cell recovery.     

Healing of osteotomy sites applying either piezosurgery or two conventional saw blades: a pilot study in rabbits

Purpose

The purpose of this study was to compare bone healing of experimental osteotomies applying either piezosurgery or two different oscillating saw blades in a rabbit model.

Methods

The 16 rabbits were randomly assigned into four groups to comply with observation periods of one, two, three and five weeks. In all animals, four osteotomy lines were performed on the left and right nasal bone using a conventional saw blade, a novel saw blade and piezosurgery.

Results

All three osteotomy techniques revealed an advanced gap healing starting after one week. The most pronounced new bone formation took place between two and three weeks, whereby piezoelectric surgery revealed a tendency to faster bone formation and remodelling. Yet, there were no significant differences between the three modalities.

Conclusions

The use of a novel as well as the piezoelectric bone-cutting instrument revealed advanced bone healing with a favourable surgical performance compared to a traditional saw.     

Impaired bone microarchitecture at the distal radius in older men with low muscle mass and grip strength: The STRAMBO study

The aim was to study the association between bone microarchitecture and muscle mass and strength in older men. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed in 810 men aged ≥60 years at the distal radius by high‐resolution peripheral computed tomography (HR‐pQCT). Areal bone mineral density (aBMD) and appendicular muscle mass (ASM) were assessed by dual‐energy X‐ray absorptiometry (DXA). Relative ASM of the upper limbs (RASM‐u.l.) was calculated as ASM of the upper limbs/(height)². Grip strength was measured by dynanometry. In multivariable models, men in the lowest RASM‐u.l. quartile had lower cross‐sectional area (CSA), cortical area (Ct.Ar), cortical thickness (Ct.Th), and trabecular area (Tb.Ar) at distal radius compared with men in the highest quartile. The trends remained significant after adjustment for grip strength. Men in the lowest quartile of the normalized grip strength (grip strength/[height]²) had lower aBMD, total vBMD, Ct.Ar, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp and Tb.Sp.SD. The associations for Ct.Ar, total vBMD, Ct.Th, Tb.vBMD, and Tb.Sp remained significant after adjustment for RASM‐u.l. In the models including RASM‐u.l. and normalized grip strength, CSA and Tb.Ar were associated with RASM‐u.l. but not with the strength. Lower Ct.Th, Tb.vBMD, and Tb.N were associated with lower grip strength but not with RASM‐u.l. Lower Ct.Ar was associated with lower grip strength and with lower RASM‐u.l. In conclusion, in older men, low RASM‐u.l. and low grip strength are associated with poor cortical and trabecular microarchitecture partly independently of each other, after adjustment for confounders. © 2013 American Society for Bone and Mineral Research