Collagenase clostridium histolyticum in patients with Dupuytren's contracture: results from POINT X, an open-label study of clinical and patient-reported outcomes.

In POINT X, a study designed to reflect clinical practice and patient treatment choices, 254 European patients received open-label collagenase for Dupuytren's contracture. The most severely affected joint was treated first in 74% of patients. In total, 52%, 41%, 7%, and 1% of patients selected the little, ring, middle, and index finger, respectively; 79% had one or two joints treated. Only 9% of patients (n = 24) received 4 or 5 injections. The mean improvement in total passive extension deficit (TPED) was 34° on day 1, improving further by day 7 to 42°. This secondary improvement was maintained by day 90 and month 6. The mean number of injections/joint was 1.2 for the metacarpophalangeal joint and 1.25 for the proximal interphalangeal joint. Median time to recovery was 4 days; the mean improvement in hand function was clinically relevant as measured by the Unité Rhumatologique des Affections de la Main (URAM) score. In total, 87% and 86% of patients and physicians, respectively, were very satisfied or satisfied with treatment at month 6, although correlation between TPED and patient satisfaction was weak (Spearman -0.18, 95% CI -0.32 to -0.06). Collagenase was well tolerated, with 10 (3.9%) patients experiencing severe adverse events. As a real-world study, the POINT X findings can be generalized to the at-large population.

Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures? A randomized, double-blind, placebo-controlled trial.

STUDY OBJECTIVE: Despite widespread use of adjunctive benzodiazepines during ketamine sedation, their efficacy in reducing recovery agitation in children has never been studied. We wished to characterize the nature and severity of recovery agitation after ketamine sedation in children treated in the emergency department and to determine whether the addition of adjunctive midazolam reduces the magnitude of such recovery agitation. METHODS: The study was a randomized, double-blind, clinical trial of adjunctive midazolam versus placebo during ketamine sedation. We enrolled 104 children aged 12 months to 15 years (median age, 6 years) at a combined university medical center and children's hospital. Subjects received either intravenous midazolam (0.05 mg/kg up to 2 mg) or placebo after intravenous administration of a ketamine loading dose (1.5 mg/kg). Treating physicians and nurses independently noted the presence of crying, hallucinations, and nightmares during recovery and graded recovery agitation by using a 100-mm visual analog scale. Preprocedure agitation and external stimulation during recovery were also graded. The time from ketamine injection until each subject met the recovery criteria was recorded. RESULTS: Fifty-three subjects received midazolam, and 51 received placebo. Potentially confounding variables were similar between the groups. Sedation efficacy, adverse effects, and recovery time were also similar between groups. Interobserver agreement between physician and nurse assessments was substantial. Median physician assessment of recovery agitation was 4 mm (interquartile range, 2 to 19) in the midazolam group and 5 mm (interquartile range, 3 to 14) in the placebo group (difference -1; 95% confidence interval -3 to 2; P =.705). Recovery agitation was moderately correlated with preprocedure agitation (rho=0.486) but not with external stimulation during recovery (rho=0.147). CONCLUSION: Recovery agitation is common but generally of very low magnitude after ketamine sedation in children in the ED. We observed a median physician rating of 5 mm on a 100-mm visual analog scale, a score that we believe to be clinically insignificant. The degree of recovery agitation after ketamine sedation is significantly related to the degree of preprocedure agitation. In this study, concurrent midazolam did not diminish such agitation and had no measurably beneficial effect. Use of adjunctive benzodiazepines in pediatric ketamine sedation appears unnecessary.

The effect of blood transfusion on tumor growth in sarcoma-bearing rats.

BACKGROUND: The effect of blood transfusion on tumor growth is controversial. Under experimental conditions, even similar animal models can give varied results. This study was undertaken to characterize the nature of the effect of blood transfusion on tumor growth. METHODS: Sixty-five Fischer 344 rats subcutaneously implanted with a methylcholanthrene-induced sarcoma were studied with additive blood transfusion at 1% tumor burden in two separate experiments. In experiment 1, the effects of syngeneic fresh whole blood transfusion (5, 10, and 15 ml/kg) and allogeneic (5 ml/kg) were tested. To determine if stored blood influenced the results, experiment 2 was performed with syngeneic blood transfusion (15 ml/kg) and allogeneic blood transfusion at 5 ml/kg. Tumor dimensions were determined daily by external measurement, and tumor weight and growth rate were calculated. RESULTS: No significant differences in final tumor weights or tumor growth rates were found in transfused rats compared with controls. This held true for syngeneic blood transfusion regardless of dose, allogeneic blood transfusion, and regardless of whether the blood was fresh or stored. CONCLUSIONS: Additive blood transfusion does not affect tumor growth in this animal model. This finding, together with the general inconclusiveness in the reported literature on this topic, speaks against a dominant role for the effect of blood transfusion on tumor behavior.

Effect of calcium citrate supplementation on urinary calcium oxalate saturation in female stone formers: implications for prevention of osteoporosis.

In 14 women aged 37-68 y with a history of renal calcium calculi, bone densities were 12.0% below those of age-matched control subjects at the L2-4 lumbar spine (P = 0.007) and 6.4% less at the femoral neck (P = 0.095). A low-oxalate diet was supplemented with 1 g Ca/d as citrate. In 6 mo, plasma 1,25(OH)2D concentrations fell from 53.2 +/- 18.8 to 41.9 +/- 15.2 ng/L (P = 0.02) and parathyroid hormone from 39.1 +/- 17.0 to 30.8 +/- 12.5 ng/L (P = 0.02). Calcium oxalate saturation was 2.15 +/- 1.38 at baseline, 2.27 +/- 1.00 at 1 mo, and 2.06 +/- 1.57 at 6 mo. The increase in urinary calcium at 1 mo from 4.411 +/- 1.87 to 6.514 +/- 2.82 mmol/24 h (P = 0.01) was offset by a parallel increase in citrate excretion from 2.909 +/- 1.45 to 3.455 +/- 1.34 mmol/24 h (P = 0.03). Calcium citrate supplementation did not increase the lithogenicity of the women in this protocol.

A national survey of attitudes and practices of primary-care physicians relating to nutrition: strategies for enhancing the use of clinical nutrition in medical practice.

A nationwide mail survey was used to determine the degree to which primary-care physicians indicated that they practice the "core competencies" in clinical nutrition identified by Young et al (Am J Clin Nutr 1983;38:800-10). We also surveyed the nutrition-related attitudes of these physicians. Although the 3416 physicians who responded to the survey tended to report favorable attitudes toward using nutrition in their practice, these favorable attitudes were not consistent with their own reports of clinical performance. Neither the positive- or negative-attitude score correlated highly with the reported behavior-practice score. The clinical practices reported by those surveyed are well below the minimum level defined by the Young et al essential core competencies in clinical nutrition. The attitudes, practices, and demographic characteristics associated with the clinical performance variables suggest educational strategies for improving the competence of primary-care physicians and medical students in clinical nutrition.