Comparative impact of 2 botulinum toxin injection techniques for elbow flexor hypertonia

Mayer NH, Whyte J, Wannstedt G, Ellis CA. Comparative impact of 2 botulinum toxin injection techniques for elbow flexor hypertonia.

Objective

To compare 2 techniques of botulinum toxin injection for elbow flexor hypertonia.

Design

Parallel-group, randomized, controlled trial with blinded outcome assessment.

Setting

Laboratory, tertiary rehabilitation hospital.

Participants

Adults (N=31) with acquired brain injury (21 with traumatic brain injury, 8 with stroke, 2 with hypoxic encephalopathy) provided 36 sets of elbow flexors with Ashworth Scale scores equal to 3.

Intervention

Botulinum toxin type A (BTX-A) was injected with a motor point or a multisite injection technique after obtaining 2 baseline evaluations of the main outcome measures. Motor point technique involved decremental electric stimulation with delivery of 60U of BTX-A (Botox) in 2.4mL or 30U BTX-A in 1.2mL of preservative-free saline at single biceps and brachioradialis motor points, respectively. Distributed injection was performed using electromyographic feedback. Fifteen units in 0.6mL were delivered to each of 4 biceps sites and 2 brachioradialis sites. Total dose (90U) and total injection volume (3.6mL) were identical across groups. Only sites and injection techniques varied. The brachialis was not injected in either group.

Main Outcome Measures

Ashworth Scale, Tardieu catch angle, and root mean square surface electromyographic activity of the biceps, brachialis, and brachioradialis.

Results

Postintervention testing at 3 weeks showed no significant differences between groups (P range, .31-.82 across 3 outcome measures). However, within each group, significant treatment effects were observed on all outcome measures (all P<.01). For the uninjected brachialis muscle, electromyographic reduction was greater for the distributed group.

Conclusions

In 31 adults with acquired brain injury, single motor point and multisite distributed injections of low-dose, high-volume BTX-A had similar impact. Findings suggest that low-dose, high-volume strategies may have a potential role in reducing drug cost and helping clinicians stay within accepted limits for total body dose in patients with upper motoneuron syndrome requiring many injections.     

Investigating the performance of a wrist stabilization device for image-guided percutaneous scaphoid fixation

Purpose   

Conventional navigated surgery relies on placement of a reference marker on the anatomy of interest. However, placement of such a marker is not readily feasible in small anatomic regions such as the scaphoid bone of the wrist. This study aimed to develop an alternative mechanism for patient tracking that could be used to perform navigated percutaneous scaphoid fixation.

Methods   

A prototype wrist stabilization device was developed to immobilize the scaphoid relative to a reference marker attached to the device. A position measurement system and 3D fluoroscopy were used to study the accuracy and limitations of wrist stabilization during simulated clinical usage with a cadaver specimen. Reference markers mounted on the device were used to measure intra-device motion. Radiometallic beads implanted in the scaphoid were used to measure patient-device motion. Navigated planning and guidance of scaphoid fixation were performed in five cadaver and eight “ideally immobilized” plastic specimens. Postoperative 3D fluoroscopy was used to assess the accuracy of navigated drilling.

Results   

The average intra-device motion was 1.9 mm during load application, which was elastically recovered upon release of the load. Scaphoid motion relative to the reference marker was predominately rotational with an average displacement of 1.25 mm and $2.0^{\circ }$ . There was no significant difference in the accuracy of navigated drilling between the cadaver specimens and the ideally immobilized group.

Conclusions   

The prototype wrist stabilization device meets the criteria for effective wrist stabilization. This study provides insight concerning proper use of the device to minimize scaphoid displacement and design recommendations to improve immobilization.     

Underrecognition of leptospirosis during a dengue fever outbreak in Hawaii, 2001-2002

During the 10-year period from 1997 through 2006, the reported mean annual incidence rate of leptospirosis in the state of Hawaii was 3.3/100,000 with a range of 22-60 infections reported each year. Because the clinical presentation is highly variable, however, leptospirosis illness is challenging to recognize and may be underdiagnosed. To assess whether the incidence may be substantially higher than reported figures indicate, we retrospectively studied the prevalence of anti-Leptospira IgM antibodies among specimens obtained over a 12-month period (May 2001 to April 2002) from patients presenting with febrile illness during a dengue fever outbreak in Hawaii. Of 1206 patients testing negative or indeterminate for dengue, 54 (4.5%; 95% confidence interval: 3.3%-5.7%) were positive for anti-Leptospira IgM antibodies using a commercially available dipstick enzyme-linked immunosorbent assay (ELISA). The most common clinical symptoms reported by laboratory-positive leptospirosis patients were fever (92%), headache (88%), and myalgia (83%). Three clinical symptoms were significantly less common among persons laboratory positive for leptospirosis when compared with the 122 patients who had been diagnosed with dengue fever during the outbreak: rash (p < 0.0001), chills (p = 0.05), and petechiae (p = 0.0005). Laboratory-positive leptospirosis infections were identified in persons exposed on each of the 5 most populous islands and illness onsets spanned a 10-month period, reflecting an endemic pattern of disease. If added to the figures obtained via routine passive surveillance, the number of leptospirosis infections identified through this study would more than double the annual incidence rate for Hawaii during 2001. These findings indicate that many leptospiral infections in Hawaii go undiagnosed. Physicians should maintain a high index of suspicion for leptospirosis when assessing patients presenting with acute febrile illness among residents and visitors to Hawaii.     

When an ICD is not the answer... hypothyroidism-induced cardiomyopathy and torsades de pointes

Introduction: An increasing number of patients with left ventricular (LV) dysfunction are referred for placement of an implantable cardioverter‐defibrillator (ICD). Case Report: A 78‐year‐old female with fatigue, palpitations, and presyncope was referred for consideration of an ICD because of a cardiomyopathy and nonsustained ventricular tachycardia (VT). Her evaluation revealed severe hypothyroidism, marked QT prolongation, and episodes of torsades de pointes. With levothyroxine therapy, her ventricular arrhythmias rapidly abated, with subsequent normalization of LV function and the QT interval. Conclusions: This report highlights the critical importance of detecting hypothyroidism as an unusual cause for reversible cardiomyopathy and ventricular arrhythmias.     

Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura

Controversy exists regarding management of children newly diagnosed with immune thrombocytopenic purpura (ITP). Drug treatment is usually administered to prevent severe hemorrhage, although the definition and frequency of severe bleeding are poorly characterized. Accordingly, the Intercontinental Childhood ITP Study Group (ICIS) conducted a prospective registry defining severe hemorrhage at diagnosis and during the following 28 days in children with ITP. Of 1106 ITP patients enrolled, 863 were eligible and evaluable for bleeding severity assessment at diagnosis and during the subsequent 4 weeks. Twenty-five children (2.9%) had severe bleeding at diagnosis. Among 505 patients with a platelet count less than or equal to 20 000/mm(3) and no or mild bleeding at diagnosis, 3 (0.6%), had new severe hemorrhagic events during the ensuing 28 days. Subsequent development of severe hemorrhage was unrelated to initial management (P = .82). These results show that severe bleeding is uncommon at diagnosis in children with ITP and rare during the next 4 weeks irrespective of treatment given. We conclude that it would be difficult to design an adequately powered therapeutic trial aimed at demonstrating prevention of severe bleeding during the first 4 weeks after diagnosis. This finding suggests that future studies of ITP management should emphasize other outcomes.     

Impact of long-term treatment with neurotoxic dideoxynucleoside antiretrovirals: implications for clinical care in resource-limited settings

Objectives

A minority of HIV‐infected patients taking an antiretroviral (ARV) regimen containing dideoxynucleosides (d‐drugs) such as stavudine (d4T) and didanosine (DDI) experiences dose‐limiting neuropathic pain and paraesthesias, usually within weeks of starting these drugs. Because d‐drugs are among the few affordable options available in developing countries, continuing d‐drug therapy would be a desirable strategy for many HIV‐infected individuals. Therefore, we evaluated the safety of continuing d‐drug therapy.

Methods

In a US cohort, we compared the rates of worsening neuropathic symptoms and signs in HIV‐infected individuals on stable ARV regimens that did (n=252) or did not (n=250) include d‐drugs. Rates of worsening were compared using proportional hazards model and the log‐rank test.

Results

The risk ratios (RR) were not significantly larger for worsening neuropathy signs [0.94; 95% confidence interval (CI) 0.84–1.07] or symptoms (0.99; 95% CI 0.88–1.14) in patients taking d‐drugs continuously compared to those not taking d‐drugs.

Conclusions

Continued d‐drug exposure among patients tolerating an initial trial did not increase the risk of worsening neuropathy compared to non‐d‐drug‐containing regimens. If applicable in developing countries, these findings suggest that in most patients d‐drugs can be continued safely in the long term without increasing the risk of worsening neuropathy.     

Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33

We performed a three-phase genome-wide association study (GWAS) using cases and controls from a genetically isolated population, Ashkenazi Jews (AJ), to identify loci associated with breast cancer risk. In the first phase, we compared allele frequencies of 150,080 SNPs in 249 high-risk, BRCA1/2 mutation-negative AJ familial cases and 299 cancer-free AJ controls using chi(2) and the Cochran-Armitage trend tests. In the second phase, we genotyped 343 SNPs from 123 regions most significantly associated from stage 1, including 4 SNPs from the FGFR2 region, in 950 consecutive AJ breast cancer cases and 979 age-matched AJ controls. We replicated major associations in a third independent set of 243 AJ cases and 187 controls. We obtained a significant allele P value of association with AJ breast cancer in the FGFR2 region (P = 1.5 x 10(-5), odds ratio (OR) 1.26, 95% confidence interval (CI) 1.13-1.40 at rs1078806 for all phases combined). In addition, we found a risk locus in a region of chromosome 6q22.33 (P = 2.9 x 10(-8), OR 1.41, 95% CI 1.25-1.59 at rs2180341). Using several SNPs at each implicated locus, we were able to verify associations and impute haplotypes. The major haplotype at the 6q22.33 locus conferred protection from disease, whereas the minor haplotype conferred risk. Candidate genes in the 6q22.33 region include ECHDC1, which encodes a protein involved in mitochondrial fatty acid oxidation, and also RNF146, which encodes a ubiquitin protein ligase, both known pathways in breast cancer pathogenesis.     

Outcome After Curative Resection for Locally Recurrent Rectal Cancer

Purpose Few biologic markers have been studied as prognostic factors in recurrent rectal carcinoma patients. We sought to determine the influence of clinical, pathologic, and biologic (p53, bcl-2, and ki-67) variables on survival after curative resection of locally recurrent rectal cancer. Methods Retrospective review of patients with locally recurrent rectal cancer who received surgery with curative intent. Results From 1988 to 1998, 134 patients with locally recurrent rectal cancer underwent operative exploration. Curative resection was performed in 85 patients. Median follow-up was 43 (range, 1.3–149) months. On multivariate analysis, negative predictors of overall survival included an elevated carcinoembryonic antigen level (P = 0.02; hazard ratio 2.41; 95 percent confidence interval, 1.19–4.89) and an R1 resection margin (P = 0.01; hazard ratio, 2.81; 95 percent confidence interval, 1.27–6.21). In 26 patients for whom biologic variables were available, p53, bcl-2, and ki-67 did not significantly impact disease-specific survival or overall survival. Five-year disease-specific survival, overall survival, and pelvic control rates were 46, 36, and 51 percent respectively. Of the 50 patients who relapsed, time to second local recurrence was longer than time to development of metastasis (median, 16.5 vs. 9 months). Median survival for patients with metastatic recurrence was 26.l vs. 41.5 months for those with a subsequent local recurrence alone. Conclusions Approximately two-thirds of patients with locally recurrent rectal cancer can be resected for cure. Preoperative carcinoembryonic antigen and an R0 resection margin were the only significant predictors of overall survival. p53, bcl-2, and ki-67 did not impact survival outcomes.