Wilcoxan Signed Rank Test Research Articles

The PESSRI study: symptom relief outcomes of a randomized crossover trial of the ring and Gellhorn pessaries

The aim of this randomized crossover trial was to compare symptom relief and change in life impact for women using the ring with support and Gellhorn pessaries. Subjects were randomized to use each pessary for 3 months. Outcome data included a visual analog satisfaction score, and quality of life questionnaires. Analysis included student's t-test, Wilcoxan Signed-rank test and logistical regression. Subjects were primarily white, parous, postmenopausal women with a mean age of 61. The median POPQ stage was III. We enrolled 134 subjects and collected 3-month data on 94 ring and 99 Gellhorn subjects. There were statistically and clinically significant improvements in the majority of the PFDI and many PFIQ scales with both pessaries, but no clinically significant differences between the two pessaries. The ring with support and Gellhorn pessaries are effective and equivalent in relieving symptoms of protrusion and voiding dysfunction.

Effect of A Simulation-based Program in Common Anesthesia Events During Orientation in An Anesthesia Training Program.

BACKGROUND: First year anesthesia residents (CA-1) enter highly stressful work and learning environments with minimal preparation for new decision-making responsibilities. Simulation-based learning leads to the building of generative skills resulting in enhanced self-efficacy. The aim of the study was to analyze the effect of simulation-based teaching of common clinical intraoperative scenarios on the resident’s self-ratings of confidence. Additionally, we surveyed the trainees for an assessment of the fidelity and usefulness of the program. METHOD: A prospective study was performed with the CA-1 residents during a 21 day period during the first month of training. The residents initially completed a precourse self-confidence survey consisting of 25 questions, scaled 1 to 10 with 1 = no confidence to 10 = fully confident. They received simulation-based instruction in the conduct of anesthesia and management of routine intraoperative problems (hypoxia, hypotension, and hypertension) using SimMan® (Laerdal Medical, Wappingers Falls, NY). The residents received 3 sessions lasting 60 minutes each. Upon completion of the course, the residents completed an identical postcourse confidence survey. At the end of the session, residents completed a survey to assess their perceptions of simulation-based education, the relevance and face validity of the clinical scenarios, and the effectiveness of the sessions (23 questions on a 1 to 5 Likert scale, 1 = strongly disagree to 5 = strongly agree). Both the mean confidence level for each resident as well as the group’s cumulative mean confidence levels were determined. The group data were analyzed by paired Student’s t test. The individual questionnaire data was analyzed by Wilcoxan signed rank test for paired data. Statistical significance was defined as P <0.05. The evaluation surveys were analyzed for frequency distributions and data reported as mean values as well as percentage of respondents who agreed or disagreed with the statements. RESULTS: All 23 trainees completed the course and surveys. The cumulative mean trainee confidence measure (N= 23) increased significantly (P <0.001) from a precourse value of 5.72 + SD 2.24 to a postcourse value of 6.95 + SD 1.94. The mean confidence measures increased in 21 of 23 residents. With respect to the individual survey questions, both the cumulative mean and individual confidence scores increased in 24 of 25 questions after the sessions. The sessions were felt to be sufficiently realistic (4.32 + 0.65 [mean, S.D.]) and the fidelity of the simulations was rated highly by 91% (Likert scores 4) of the residents. The sessions reinforced clinical concepts in the didactic program (4.32 + 0.84) and increased confidence (4.00 + 0.69) to take care of patients in 86% of the trainees (Likert scores 4). All of the residents indicated that simulation-based teaching should be mandatory during the orientation (4.64 + 0.49). CONCLUSIONS: Completion of the simulation-based course led to a significant (P <0.001) improvement in the confidence level of the trainees. The program was well received by the residents, and they expressed a strong desire to continue this type of training throughout their residency.

Mixed Hematopoietic Chimerism for Sickle Cell Disease Prevents Intravascular Hemolysis and Corrects Biomarkers of Endothelial Function.

Recent studies have highlighted the impact of chronic intravascular hemolysis on endothelial function and end-organ injury, such as pulmonary hypertension, in patients with sickle cell disease (SCD). Preservation of organ function is a critical criterion of the success of therapy. Nonmyeloablative allogeneic stem cell transplantation is relatively non-toxic and frequently results in mixed hematopoietic chimerism. However, it is not known if mixed chimerism reduces end-organ toxicity. To assess the effects of mixed chimerism on reduction in hemolysis and endothelial function, we measured multiple plasma parameters of intravascular hemolysis (free hemoglobin concentration, LDH, haptoglobin) and vascular function (sVCAM, NO consumption, arginine/ornithine ratio), recently identified to be associated with pulmonary hypertension and endothelial dysfunction, in 7 SCD patients who developed 25–90% donor engraftment. For each of the 7 patients, we identified normalization in the degree of intravascular hemolysis and endothelial function following transplant. In the analysis of 5 of the 7 patients from whom paired pre and post samples were available, LDH was found to decrease from a median of 376 U/L (range 255–850 U/L) to 162 U/L (range 122–260) (p=0.06, Wilcoxan signed rank test). Similarly, free Hb concentration was observed to decrease from a median of 29.6 μM (range 5.5 to 75.9) to 1.6 μM (range 0.71–8.22) (p=0.06). Haptoglobin rose from a median value of 5.0 mg/dL (range 5–20), to 33 mg/dL (range 7–47) (p=0.06). Parameters of vascular function were also analyzed in a similar fashion. NO bioavailability and sVCAM levels decreased from a median of 7.63 μM (range 1.9–49.7) to 1.22 μM (range 0.6–8.6) (p=0.06), and from a median of 952.1 ng/ml (range 498.2 to 1067) to 543.1 ng/ml (range 193.9 to 627.2) (p= 0.06), respectively. Average arginine/ornithine ratio was inverted prior to transplant to a level of 0.95 (range 0.10–1.4), and normalized following transplantation to a ratio of 2.2 (range 0.14–2.3) at levels that approached significance (p= 0.19). After d180, Pt 1 experienced graft rejection, and all hemolysis parameters again approached pre-transplant levels, demonstrating that reduction in intravascular hemolysis was directly attributable to the presence of circulating donor erythrocytes. Studies of RBC chimerism more accurately assessed the functional impact of donor hematopoiesis. RBC chimerism was serially measured by quantifying donor-derived beta-globin RNA in PBMC. Surprisingly, this revealed a ~2-fold higher level of donor erythroid precursor expression (70–100%) compared to the level of total donor cell engraftment, attributable to the improved survival of engrafted cells. This near-to full replacement of peripheral erythrocytes with donor derived RBCs accounts for the improvements in hemolysis. Our data reveal that levels of donor engraftment as low as 25% can ameliorate the degree of hemolysis and can potentially protect against ongoing chronic end-organ damage. Taken together, our data mechanistically supports mixed chimerism as a suitable endpoint of stem cell transplantation for SCD.

Varicose Veins Possess Greater Quantities of MMP-1 Than Normal Veins and Demonstrate Regional Variation in MMP-1 and MMP-13

Background. Studies have reported that structural proteins such as elastin and collagen are decreased in varicose veins compared to normal controls. We hypothesized that the changes observed in varicose vein wall composition may be related to alterations in extracellular matrix remodeling proteins, such as the matrix metalloproteases and serine proteases. In addition we hypothesized that there may be regional variation in the expression of these enzymes within the leg. Patients and materials. One-centimeter segments of the proximal and distal greater saphenous vein (GSV) were obtained from patients undergoing ligation and stripping for venous insufficiency (vv) ( n = 15) or GSV harvest in conjunction with coronary artery bypass grafting (CABG) ( n = 7). All vv patients had incompetence of the GSV by color flow duplex. Vein specimens were examined for MMP-1, 3, and 13, tryptase, and GAPDH mRNA using semiquantitative RT–PCR analysis. Quantification of MMP-1 and 13 (active/latent forms) and tryptase was performed using Western blot analysis. Western blots were analyzed using scanning densitometry and standardized to normal controls and values expressed as the median densitometric index (D.I.). Nonparametric statistical methods (Wilcoxan signed rank test and Mann–Whitney U test) were used for analysis. Results. We were able to amplify MMP-1, MMP-13, and tryptase mRNA from both proximal and distal segments of all greater saphenous veins studied. MMP-3 mRNA, however, was not found in either segment of any of the veins examined. A semiquantitative analysis of RT–PCR products comparing the ratio of MMP-1, MMP-13, or tryptase mRNA to GAPDH mRNA showed no difference between cases and controls nor proximal vs distal vein segments. Western blot analysis revealed larger quantities of MMP-1 in varicose veins than in nondiseased veins from CABG patients (48.0 ± 36.7 D.I. vs 12.5 ± 6.8 D.I., P = 0.036). Investigation into the regional variation of proteases revealed lower amounts of MMP-1 in distal than in proximal vein segments (37.9 ± 35.0 D.I. vs 44.1 ± 41.6 D.I., P = 0.01). Similarly, we found significantly less MMP-13 in distal segments of varicose veins than in proximal segments (152.8 ± 130.0 D.I. vs 206.7 ± 173.3 D.I., P = 0.006). Conclusions. This study found that MMP-1 protein is increased in varicose veins when compared to controls despite no differences in mRNA expression. In addition we found that there is regional variation of MMP-1 and MMP-13 in diseased varicose veins. Lower leg veins have significantly reduced amounts of these proteolytic enzymes when compared to veins of the upper thigh. These data suggest that posttranscriptional regulatory controls could be responsible for the observed differences.

Concomitant use of divalproex sodium and lamotrigine in developmentally disabled patients with epilepsy: a retrospective evaluation of efficacy and tolerability

Objective. Epilepsy in institutionalized severe developmentally disabled patients poses a therapeutic challenge. Frequently these patients have multiple seizure (sz) types that are often intractable. Both divalproex sodium (VPA) and lamotrigine (LTG) have demonstrated efficacy. We sought to examine the efficacy of this specific combination in a group of institutionalized, developmentally disabled patients with epilepsy. Methods. Medical and pharmacy records of all patients with developmental disabilities and intractable seizures were reviewed to identify those who had received VPA and LTG. This retrospective evaluation was structured with respect to time frame and outcome measure. Phase 1 consisted of baseline monotherapy with VPA. Phase 2 consisted of titration/dose escalation. Phase 3 was treatment observation period with the combination of both. Seizure frequency and adverse effect data were obtained from nursing or residential staff records. Primary outcome measures were change in seizure frequency between Phases 1 and 3. Additional measures were percentage of patients seizure-free and those with >75% reduction in seizures. A Wilcoxan signed rank test was used for statistical analysis. Results. Of 293 patients, 25 (12 M/13 F, 31.7±10.2 years) had VPA monotherapy following which LTG was added. Mean doses of VPA and LTG were 1474±728 and 165±111 mg/day, respectively. Baseline seizure frequency ranged from 1 to 25 per month. Mean seizure frequency significantly decreased ( 6.5± vs 2 .0±4.0 seizures/month, P<0.001). Sixty-four percent of these patients had ⩾75% reduction in seizures 28% became seizure-free. Conclusions. The combination of VPA and LTG appears efficacious in this group of developmentally disabled patients with intractable seizures. Rash, which has been associated with this combination, was notably absent and this may reflect the slower titration schedule used.

Hibernation and disuse osteoporosis

In an attempt to determine 1) if disuse osteoporosis occurs naturally during hibernation and 2) if it can be induced by limb immobilization in active and hibernating ground squirrels, forty-six thirteenlined ground squirrels were divided into five experimental groups. Group one was the active control group (AC) (ten animals). Group two was the active immobilized (AI) group and was subjected to a unilateral sciatic nerve section (ten animals). Group three was the hibernating control group and was allowed to hibernate undisturbed for 30 days (HC) (ten animals). The fourth group was subjected to a unilateral sciatic nerve section and allowed to hibernate for 30 days; this was the hibernating immobilized group (HI). The fifth group of six animals received the identical treatment as the (HI) group but was allowed to hibernate for 150 days. The following measurements were taken: Gastrocnemius-soleus mass, body mass, tibia-fibula weight, total tibia-fibula calcium and phosphorus. In addition, the femur was observed histologically for the enlarged lacunae typical of osteoporotic bone. Statistical analysis was accomplished with the Wilcoxan sign rank test. The data were interpreted to mean: 1) Disuse osteoporosis can be induced in active ground squirrels, 2) disue osteoporosis is not evident nor can it be induced by limb immobilization during 30 days of hibernation and 3) limb immobilization did not result in significant disuse osteoporosis following 150 days of hibernation. Only a few enlarged lacunae were evident after 150 days of hibernation.