Use of silfenadil for treatment of respiratory distress after pneumonectomy for bronchogenic carcinoma

Post-pneumonectomy respiratory failure is a devastating complication of resection for lung cancer. As proven therapy is limited, we successfully employed a novel medication silfenadil that has been effective in the treatment of pulmonary hypertension.     

Effect of medical management on recurrent stone formation following percutaneous nephrolithotomy

PURPOSE: Percutaneous nephrolithotomy is a commonly used procedure for treatment of large or complex renal calculi. In some instances postoperative residual stone fragments are an unavoidable result. Yet to our knowledge no study has examined the impact of medical management on stone formation in patients with or without residual fragments following percutaneous nephrolithotomy. Thus, we have conducted the first investigation of aggressive medical management following percutaneous nephrolithotomy and its impact on stone formation rates in patients with and without residual fragments. MATERIALS AND METHODS: A total of 70 patients who underwent percutaneous nephrolithotomy and received counseling regarding selective medical management following a comprehensive metabolic evaluation, were identified. Patients were placed into 4 groups following percutaneous nephrolithotomy, that is stone-free or residual fragments, who underwent or did not undergo medical therapy. New stone formation was assessed by spontaneous stone passage in the absence of residual stone fragments, stone passage without change in the number of residual fragments, surgical removal of newly formed stones, or appearance of new stones or increase in size of stone or fragments on abdominal radiographs. Stone remission rates were also calculated. RESULTS: Selective medical therapy significantly decreased stone formation rates in the stone-free (0.67 stones per patient per year vs 0.02) and residual fragment groups (0.67 stones per patient per year vs 0.02) as determined by the Wilcoxon signed rank test (p<0.0001). Moreover, remission was observed in a higher proportion of patients in the medically treated stone-free and residual fragment groups (87% and 77%) when compared to the same groups without medical therapy (29% and 21%, chi-square test p<0.0001). CONCLUSIONS: Our findings suggest that comprehensive metabolic evaluation and aggressive medical management can control active stone formation and growth in patients with or without residual stone fragments after percutaneous nephrolithotomy. Given the inherent morbidity and increased costs attendant with repeat procedures, medical management should be instituted in patients following percutaneous nephrolithotomy without regard to stone-free status.     

Optimal adaptive design in clinical drug development: a simulation example

The objective of this article is to demonstrate optimal adaptive design as a methodology for improving the performance of phase II dose-response studies. Optimal adaptive design uses both information prior to the study and data accrued during the study to continuously update and refine the study design. Dose-response models include linear, log-linear, 4-parameter sigmoidal E(max), and exponential models. Where the response has both a placebo effect and plateau at higher doses, only the 4-parameter sigmoidal E(max) model behaves acceptably and hence is used to illustrate the methodology. Across 13 hypothetical dose-response scenarios considered, it was shown that the capability of the adaptive designs to "learn" the true dose response resulted in performances up to 180% more efficient than the best fixed optimal designs. This work exposes the common misconception that adaptive designs are somehow "risky." As shown in this simple simulation example, the converse is true. Adaptive designs perform extremely well both when prior information is accurate and inaccurate. This leads to improved dose-response models and dose selection in phase III. This benefits sponsors, regulators, and subjects alike by reducing sample size, increasing information, and providing better dose guidance.     

Influence of anticipation on movement patterns in subjects with ACL deficiency classified as noncopers

STUDY DESIGN: Two-factor, mixed experimental design. OBJECTIVES: To compare movement patterns of subjects who are anterior cruciate ligament (ACL) deficient and classified as noncopers to controls during early stance of anticipated and unanticipated straight and cutting tasks. BACKGROUND: Altered neuromuscular control of subjects that are ACL deficient and noncoper theoretically influences movement patterns during unanticipated tasks. METHODS AND MEASURES: The study included 16 subjects who are ACL deficient, classified as noncopers, and 20 healthy controls. Data were collected using an Optotrak Motion Analysis System and force plate integrated with Motion Monitor Software to generate knee joint angles, moments, and power. Each testing session included anticipated tasks, straight walking task (ST), and 45 degrees side-step cutting tasks (SSC), followed by a set of unexpected straight walking (STU) and unexpected sidestep cutting (SSCU) tasks in a random order. For all tasks speed was maintained at 2 m/s. Peak knee angle, moment, and power variables during early stance were compared using 2-way mixed-effects ANOVA models. RESULTS: For both the straight and sidestep tasks, the noncoper group did not show a dependence on whether the task was anticipated or unanticipated (group-by-condition interaction) for the knee angle (straight, P = .067; side-step cutting, P = .103), moment (straight, P = .079; side-step cutting, P = .996), and powers (straight, P = .181; side-step cutting, P = .183) during the loading response phase. However, during both straight and side-step cutting tasks, the subjects in the noncoper group used significantly lower knee flexion angles (straight, P = .002; side-step cutting, P = .019), knee moments (straight, P = .005; side-step cutting, P < .001), and knee powers (straight, P = .013; side-step cutting, P <.001). CONCLUSIONS: This study suggests subjects that are ACL deficient and classified as noncopers use a common abnormal movement pattern of lower knee extensor loading even during unanticipated tasks.     

Prevalence and factors associated with renal impairment in HIV‐infected patients,ANRS C03 Aquitaine Cohort,France

Objectives

The aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV‐infected adult patients and to investigate the associated factors.

Methods

A cross‐sectional survey was conducted in a French hospital‐based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft–Gault formula. Four stages of RI were defined: mild (60–90 mL/min), moderate (30–60), severe (15–30) and end stage (<15). Logistic regression models were used to investigate factors associated with RI.

Results

The male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/μL and HIV plasma viral load (VL) was<50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end‐stage. Mild RI was associated with female gender [odds ratio (OR)=3.3: 95% CI 2.6–4.3)], age >50 years (OR=9.8: 7.4–13.0) and 40–50 years (OR=1.9: 1.5–2.4), body mass index (BMI) <22 kg/m² (OR=3.3: 2.7–4.3) and tenofovir exposure (OR=1.4: 1.0–1.9 for <1 year and OR=1.5: 1.2–2.0 for >1 year). Advanced RI (CC <60 mL/min) was associated with age >50 years (OR=5.6: 2.9–10.9) and 40–50 years (OR=2.2: 1.1–1.4), BMI <22 kg/m² (OR=1.5: 1.0–2.4), hypertension (OR=2.5: 1.4–2.5) and indinavir (IDV) exposure >1 year (OR=2.3: 1.5–3.6).

Conclusion

This survey confirms the high prevalence of RI in HIV‐infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.