Influence of open chest conditions on pulse pressure variations

Objectives

Pulse pressure variations are used to assess fluid responsiveness in mechanically ventilated patients. The accuracy of this index in open chest conditions remained unclear. The aim of the study was to evaluate the effect of open chest conditions on pulse pressure variations.

Study design

Non-interventional prospective study.

Methods and patients

Twenty-eight mechanically ventilated patients scheduled for open-heart surgery were included. Pulse pressure variations, peak aortic velocity, and stroke volume were measured before and after thoracotomy with pericardotomy. Measurements were made at each step and compared.

Results

Neither pulse pressure variation nor peak aortic velocity and nor stroke volume variation were modified by open chest conditions (median = 5% [interquartile range = 6] vs 4% [6], p = NS), (20% [11] vs 17% [12], p = NS and 11% [7] vs 10% [3], p = NS) respectively. Pulse pressure variations were correlated to stroke volume before thoracotomy (r’ = −0.432; p = 0.02) and after thorocatomy (r’ = −0.433, p = 0.02).

Conclusion

In these studied patients, preload dependancy indices were not modified by open chest conditions. Pulse pressure variations remained correlated to stroke volume even after thoracotomy.     

The bladder pain/interstitial cystitis symptom score: development, validation, and identification of a cut score

Background

There is a need to develop a self-report measure that reliably identifies moderate to severe bladder pain syndrome (BPS) patients for inclusion into clinical trials to assess the efficacy of new BPS treatments.

Objective

To develop and validate a patient-reported symptom-based instrument, the Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS), for clinical trial eligibility of BPS patients.

Design, setting, and participants

Stage 1: Qualitative concept elicitation (CE) interviews were conducted with BPS patients in France (n = 12), Germany (n = 12), and the United States (US) (n = 20), and overactive bladder (OAB) (n = 10) patients in the US for comparison. Stage 2: Cognitive debriefing (CD) interviews were performed with US BPS patients (n = 20). Stage 3: An observational study with 99 BPS, 99 OAB, and 100 healthy participants in the US was used to perform item reduction, identify cut scores, and validate the measure. A cut score was defined using logistic regression and receiver operating characteristic curves. Psychometric properties, including test-retest reliability, were assessed.

Measurements

In addition to the BPIC-SS, the Pelvic Pain and Urgency/Frequency Patient Symptom Scale, the Interstitial Cystitis Symptom Index, a Clinician Global Impression of Severity, and a Patient Global Impression of Change were included in the observational study.

Results and limitations

In CE, reported symptoms were bladder pain, persistent urge to urinate, and high urinary frequency. In CD, 13 items were deleted, and 15 were retained. Based on validation analyses, qualitative findings, and clinical relevance, the instrument was reduced to eight items that had strong sensitivity (0.72) and specificity (0.86) with a cut score ≥19 to determine clinical trial inclusion. Psychometric properties were strong.

Conclusions

The BPIC-SS is a reliable, valid, and appropriate questionnaire to select BPS/interstitial cystitis patients for clinical trials.     

Residual tumor size and IGCCCG risk classification predict additional vascular procedures in patients with germ cell tumors and residual tumor resection: a multicenter analysis of the German Testicular Cancer Study Group

Background

Residual tumor resection (RTR) after chemotherapy in patients with advanced germ cell tumors (GCT) is an important part of the multimodal treatment. To provide a complete resection of residual tumor, additional surgical procedures are sometimes necessary. In particular, additional vascular interventions are high-risk procedures that require multidisciplinary planning and adequate resources to optimize outcome.

Objectives

The aim was to identify parameters that predict additional vascular procedures during RTR in GCT patients.

Design, setting, and participants

A retrospective analysis was performed in 402 GCT patients who underwent 414 RTRs in 9 German Testicular Cancer Study Group (GTCSG) centers. Overall, 339 of 414 RTRs were evaluable with complete perioperative data sets.

Measurements

The RTR database was queried for additional vascular procedures (inferior vena cava [IVC] interventions, aortic prosthesis) and correlated to International Germ Cell Cancer Collaborative Group (IGCCCG) classification and residual tumor volume.

Results and limitations

In 40 RTRs, major vascular procedures (23 IVC resections with or without prosthesis, 11 partial IVC resections, and 6 aortic prostheses) were performed. In univariate analysis, the necessity of IVC intervention was significantly correlated with IGCCCG (14.1% intermediate/poor vs 4.8% good; p = 0.0047) and residual tumor size (3.7% size <5 cm vs 17.9% size ≥5 cm; p < 0.0001). In multivariate analysis, IVC intervention was significantly associated with residual tumor size ≥5 cm (odds ratio [OR]: 4.61; p = 0.0007). In a predictive model combining residual tumor size and IGCCCG classification, every fifth patient (20.4%) with a residual tumor size ≥5 cm and intermediate or poor prognosis needed an IVC intervention during RTR. The need for an aortic prosthesis showed no correlation to either IGCCCG (p = 0.1811) or tumor size (p = 0.0651).

Conclusions

The necessity for IVC intervention during RTR is correlated to residual tumor size and initial IGCCCG classification. Patients with high-volume residual tumors and intermediate or poor risk features must initially be identified as high-risk patients for vascular procedures and therefore should be referred to specialized surgical centers with the ad hoc possibility of vascular interventions.     

Sunitinib in urothelial cancer: clinical, pharmacokinetic, and immunohistochemical study of predictors of response

Background

Sunitinib has activity in patients with metastatic urothelial cancer (UC), but most patients do not respond.

Objective

To identify predictors of response to sunitinib.

Design, setting, and participants

Seventy-seven patients with advanced UC received sunitinib on one of two schedules at a single institution. Blood pressure (BP), immunohistochemistry (IHC), and pharmacokinetic (PK) results were correlated with response to sunitinib.

Measurements

BP was assessed on day 1 and 28 of each cycle and on day 14 of cycle 1. IHC was performed on 55 samples from 38 cases using mammalian target of rapamycin and hypoxia-inducible factor (HIF) pathway marker antibodies. Blood samples for PK analysis were collected from 15 patients at three time points. Response was assessed using Response Evaluation Criteria in Solid Tumors criteria.

Results and limitations

Sunitinib-induced hypertension predicted improved response when hypertension was categorized as a discrete (p = 0.02) or continuous variable (p = 0.005 [systolic BP] and p = 0.007 [diastolic BP]). The odds ratio of response was 12.5 (95% confidence interval, 1.95-246.8) for grade 3/4 hypertension compared with grade 0. Response was associated with low HIF-1α expression in primary (p = 0.07) tissue. A nonstatistically significant trend was seen for an association between greater drug concentration and best response. A correlation between expression markers within the same pathways was identified, phosphorylated-4EBP1 and phosphorylated-S6 (p = 6.5 × 10⁻⁹), and vascular endothelial growth factor receptor 2 and HIF-1α (p = 0.008). Results are limited by small numbers.

Conclusions

Clinical and molecular biomarkers of response to sunitinib may have clinical relevance and require prospective validation. There is an urgent need for predictive biomarkers to guide the management of UC.     

Smoking status is a risk factor for recurrence after transurethral resection of non-muscle-invasive bladder cancer

Background

Cigarette smoking is the most well-established risk factor for developing bladder cancer.

Objective

To investigate the role of smoking status on the clinical outcome of patients with non-muscle-invasive bladder cancer.

Design, setting, and participants

Data obtained during a prospective phase 3 study with three schedules of epirubicin were used for statistical analysis. Smoking status (obtained when entering the study), other prognostic variables, and clinical outcome measures of 718 patients were analyzed. Mean follow-up was 2.5 yr.

Measurements

The primary outcome measure was recurrence-free survival (RFS).

Results and limitations

Demographics were similar for nonsmokers versus ex-smokers and current smokers, except for gender (p < 0.001) and grade (p = 0.022). In univariate analyses, RFS was significantly shorter in male patients (p = 0.020), in patients with a history of recurrences (p < 0.003), in patients with multiple tumors (p < 0.004), in patients with a history of intravesical therapy (p = 0.037), and in ex-smokers and current smokers (p = 0.005). In multivariate analyses, a history of recurrences, multiplicity, and smoking status remained significant factors for predicting RFS. Gender and initial therapy were no longer a significant influence on RFS.Because progression was uncommon (n = 25) and follow-up was short and focused only on recurrences, no conclusion can be drawn on progression-free survival. A limitation of the study were the questionnaires. They were only used when entering the study, and there were no questions about passive smoking and other causal factors.

Conclusions

In this prospective study, the significance of known factors (history of recurrences and number of tumors) in predicting RFS was confirmed. Another significant factor that appears to predict RFS is smoking status: ex-smokers and current smokers had a significantly shorter RFS compared with nonsmokers.     

Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours

Background

Her2, an alias for the protein of v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), might be an attractive therapeutic target in metastasising bladder cancer. Genotype and phenotype of primary tumours and their metastases may differ.

Objectives

Determine Her2 status in both tumour components to better assess the potential of anti-Her2 therapies.

Design, setting, and participants

Histologic examination revealed lymph node metastases in 150 patients with urothelial bladder cancer clinically staged as N0M0. A tissue microarray was constructed with four tumour samples per patient: two from the primary tumour and two from nodal metastases. Her2 status was determined at the gene level by fluorescence in situ hybridisation (FISH) and at the protein level by immunohistochemistry (IHC).

Interventions

All patients underwent cystectomy and standardised extended lymphadenectomy.

Measurements

Overall survival was assessed according to HER2 gene status and protein expression in primary bladder cancers and lymph node metastases.

Results and limitations

Her2 amplification was significantly more frequent in lymph node metastases (15.3%) than in matched primary bladder cancers (8.7%; p = 0.003). Her2 amplification in primary tumours was highly preserved in the corresponding metastases as indicated by only one amplified primary tumour without amplification of the metastasis. There was a high concordance in HER2 FISH results between both samples from the primary tumour (κ = 0.853) and from the metastases (κ = 0.930). IHC results were less concordant (κ = 0.539 and 0.830). FISH and IHC results were poorly correlated in primary tumours (κ = 0.566) and metastases (κ = 0.673). While Her2 amplification in the primary tumour significantly predicted poor outcome (p = 0.044), IHC-based survival prediction was unsuccessful.

Conclusions

Her2 amplification in metastasising bladder cancer is relatively frequent, is homogeneous in each tumour component, and predicts early death. This suggests a high potential for anti-Her2 therapies. For patient selection, FISH might be more accurate than IHC.     

Effect of Pyruvate and HEPES on Rat Lung Allograft Acidosis and Cell Death After Long-term Hypothermic Storage

Background

We have previously demonstrated that adding pyruvate to Perfadex increased graft metabolism during 24-hour storage and improved reperfusion lung function. This increased metabolism was associated with progressively lower pH of the storage solution during the preservation interval.

Objective

To determine whether more effective pH regulation would result in further improvements in lung survival after hypothermic storage.

Materials and Methods

Rat lungs were stored for 24 hours in Perfadex, Perfadex with HEPES (N-2-hydroxyethylpiperazine-propanesulfonic acid) buffer, pyruvate-modified Perfadex, and pyruvate-modified Perfadex with HEPES. Change in pH in the storage solution was measured. Structural lung injury was evaluated using hematoxylin-eosin stained tissue sections. Cell death was quantified by measuring necrotic cells using trypan blue exclusion and apoptotic cells via the TUNEL (terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling) assay.

Results

Lungs stored in Perfadex demonstrated the greatest degree of cell death. Lungs in the Pyruvate group exhibited decreased cell death despite greater acidosis. The addition of HEPES reduced cell death and preservation solution acidosis in both Perfadex and pyruvate-modified Perfadex (P < .05). Almost all cell death resulted from necrosis. Adding pyruvate to the preservation solution increases acid formation during storage, but decreases cell death. HEPES ameliorates this acidosis and decreases allograft cell destruction.

Conclusion

Increasing the preservation solution buffering capacity may be a simple strategy for improving lung preservation for transplantation.     

Salvage radical prostatectomy for radiation-recurrent prostate cancer: a multi-institutional collaboration

Background

Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined.

Objective

To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP.

Design, setting, and participants

This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers.

Intervention

Open SRP.

Measurements

BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥0.1 or ≥0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death.

Results and limitations

Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31-43), 77% (95% CI, 71-82), and 83% (95% CI, 76-88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period.

Conclusions

In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in >75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP.     

Impact of venous tumour thrombus consistency (solid vs friable) on cancer-specific survival in patients with renal cell carcinoma

Background

To our knowledge, the impact of venous tumour thrombus (VTT) consistency in patients affected by renal cell carcinoma (RCC) has never been addressed.

Objective

To analyse the effect of VTT consistency on cancer-specific survival (CSS).

Design, setting, and participants

We retrospectively analysed 174 consecutive patients with RCC and renal vein or inferior vena cava (IVC) VTT who underwent surgical treatment between 1989 and 2007 at our institute.

Intervention

All patients underwent radical nephrectomy and thrombectomy.

Measurements

Pathologic specimens were reviewed by a single uropathologist. In addition to traditional pathologic features, the morphologic aspect of the tumour thrombus was evaluated to distinguish solid from friable patterns. The prognostic role of thrombus consistency (solid vs friable) on CSS was assessed by means of Cox regression models.

Results and limitations

The VTT was solid in 107 patients (61.5%) and friable in 67 patients (38.5%). The presence of a friable VTT increased the risk of having synchronous nodal or distant metastases, higher tumour grade, higher pathologic stage, and simultaneous perinephric fat invasion (all p < 0.05). The median follow-up was 24 mo. The median CSS was 33 mo; the median CSS was 8 mo in patients with a friable VTT and 55 mo in patients with a solid VTT (p < 0.001). On multivariable analyses, the presence of a friable VTT was an independent predictor of CSS (p = 0.02). The power of our conclusion may be somewhat limited by the relatively small study population and the retrospective nature of the study.

Conclusions

In patients with RCC and VTT, the presence of a friable thrombus is an independent predictor of CSS. If our finding is confirmed by further studies, the consistency of the tumour thrombus should be introduced into routine pathologic reports to provide better patient risk stratification.     

Preoperative predictive factors of ambulatory laparoscopic cholecystectomy

Background:

The aim of our study was to review our experience and to determine preoperative predictive factors for ambulatorization of laparoscopic cholecystectomy (LC).

Methods:

Between January 1999 and June 2002, 305 consecutive LC were performed as outpatient procedures. We performed univariant and multivariant analysis of preoperative clinical, analytical and ultrasonographic variables. The preoperative scoring system developed allowed us to calculate the ambulatorization probability of LC in each individual patient.

Results:

265 patients were strictly ambulatory (86.8%). Thirty-five patients required overnight admission (11.4%), most of them due to social factors, and five patients were admitted. Preoperative factors related to overnight stay or admission were: age over 65 years (p = 0.011), past history of biliary complications (p = 0.001), previous admission due to complicated biliary disease (p = 0.001), previous supramesocholic abdominal surgery (p = 0.011) and ultrasonographic findings of gallbladder thickened wall and/or shrunken gallbladder (p = 0.041). Right classification index of the predictive system was 87.5% reaching a sensibility of 87.8% and specificity of 56.6%.

Conclusions:

Outpatient LC is safe and feasible. Age, previous biliary history and ultrasonographic findings are independent preoperative factors influencing ambulatorization rate.     

Prediction of maximal aerobic capacity in severely burned children

Introduction

Maximal oxygen uptake (VO₂ peak) is an indicator of cardiorespiratory fitness, but requires expensive equipment and a relatively high technical skill level.

Purpose

The aim of this study is to provide a formula for estimating VO₂ peak in burned children, using information obtained without expensive equipment.

Methods

Children, with ≥40% total surface area burned (TBSA), underwent a modified Bruce treadmill test to assess VO₂ peak at 6 months after injury. We recorded gender, age, %TBSA, %3rd degree burn, height, weight, treadmill time, maximal speed, maximal grade, and peak heart rate, and applied McHenry's select algorithm to extract important independent variables and Robust multiple regression to establish prediction equations.

Results

42 children; 7-17 years old were tested. Robust multiple regression model provided the equation: VO₂ = 10.33 − 0.62 × age (years) + 1.88 × treadmill time (min) + 2.3 (gender; females = 0, males = 1). The correlation between measured and estimated VO₂ peak was R = 0.80. We then validated the equation with a group of 33 burned children, which yielded a correlation between measured and estimated VO₂ peak of R = 0.79.

Conclusions

Using only a treadmill and easily gathered information, VO₂ peak can be estimated in children with burns.     

Prognostic factors for mortality following falls from height

Aim

To identify the potential prognostic factors for mortality after falls from height.

Method

A retrospective clinical observational study included victims of fall of >6 m from October 2000 to December 2007. Variables studied comprised each casualty's age, gender, height of fall, Glasgow Coma Scale (GCS) score, Abbreviated Injury Scale scores, Injury Severity Score, heart rate, Mean Arterial Pressure (MAP), White Blood Cell (WBC) count, haemoglobin, serum glucose, Creatine Kinase and duration of hospital stay. The relationships between these variables and outcomes were evaluated.

Results

Among the 66 patients studied the mortality rate was 22.7%, i.e. 7 out-of-hospital and 8 in-hospital deaths. In univariate analysis, Glasgow Coma Score ≤14, Injury Severity Score ≥16, head/neck Abbreviated Injury Scale score ≥4, chest Abbreviated Injury Scale score ≥4, heart rate ≥100 or ≤50 beats/min, Mean Arterial Pressure ≤60 and serum glucose ≥140 mg/dl were significantly related to mortality. In multivariate analysis, head/neck Abbreviated Injury Scale score ≥4 was independently correlated with mortality.

Conclusions

Severe head injury (head/neck Abbreviated Injury Scale score ≥4) is a significant factor for mortality following falls from >6 m.     

Stepwise approach for nerve sparing without countertraction during robot-assisted radical prostatectomy: technique and outcomes

Background

Although subtle technical variation affects potency preservation during robot-assisted laparoscopic radical prostatectomy (RARP), most prostatectomy studies focus on achieving the optimal anatomic nerve-sparing dissection plane. However, the impact of active assistant/surgeon neurovascular bundle (NVB) countertraction on sexual function outcomes has not been studied or quantified.

Objective

To illustrate technique and compare sexual function outcomes for nerve sparing without (NS-0C) versus with (NS-C) assistant and/or surgeon NVB countertraction.

Design, setting, and participants

This is a retrospective study of 342 NS-0C versus 268 NS-C RARP procedures performed between August 2008 and February 2011.

Surgical procedure

RARP.

Measurements

We used the Expanded Prostate Cancer Index Composite (EPIC) sexual function and potency scores, estimated blood loss (EBL), operative time, and positive surgical margin (PSM).

Results and limitations

In unadjusted analysis, men undergoing NS-0C versus NS-C were older, had worse baseline sexual function, higher biopsy and pathologic Gleason grade, and higher preoperative prostate-specific antigen (PSA) levels (all p ≤ 0.023). However, NS-0C versus NS-C was associated with higher 5-mo sexual function scores (20 vs 10; p < 0.001), and this difference was accentuated for bilateral intrafascial nerve sparing in preoperatively potent men (35.8 vs 16.6; p < 0.001). Similarly, 5-mo potency for preoperatively potent men was better with bilateral intrafascial NS-0C versus NS-C (45.0% vs 28.4%; p = 0.039). However, no difference in sexual function or potency was observed at 12 mo. In adjusted analyses, NS-0C versus NS-C was associated with improved 5-mo sexual function (parameter estimate: 10.90; standard error: 2.16; p < 0.001) and potency (odds ratio: 1.69; 95% confidence interval, 1.01-2.83; p = 0.046). NS-0C versus NS-WC was associated with shorter operative times (p = 0.001) and higher EBL (p = 0.001); however, there were no significant differences in PSM. Limitations include the retrospective, single-surgeon study design and smaller numbers for 12-mo comparison.

Conclusions

Reliance on countertraction to facilitate dissecting NVB away from the prostate leads to neuropraxia and delayed recovery of sexual function and potency. Subtle technical modification to dissect the prostate away from the NVB without countertraction enables earlier return of sexual function and potency.     

Objective measures of renal mass anatomic complexity predict rates of major complications following partial nephrectomy

Background

The association between tumor complexity and postoperative complications after partial nephrectomy (PN) has not been well characterized.

Objective

We evaluated whether increasing renal tumor complexity, quantitated by nephrometry score (NS), is associated with increased complication rates following PN using the Clavien-Dindo classification system (CCS).

Design, setting, and participants

We queried our prospectively maintained kidney cancer database for patients undergoing PN from 2007 to 2010 for whom NS was available.

Interventions

All patients underwent PN.

Measurements

Tumors were categorized into low- (NS: 4-6), moderate- (NS: 7-9), and high-complexity (NS: 10-12) lesions. Complication rates within 30 d were graded (CCS: I-5), stratified as minor (CCS: I or 2) or major (CCS: 3-5), and compared between groups.

Results and limitations

A total of 390 patients (mean age: 58.0 ± 11.9 yr; 66.9% male) undergoing PN (44.6% open, 55.4% robotic) for low- (28%), moderate- (55.6%), and high-complexity (16.4%) tumors (mean tumor size: 3.74 ± 2.4 cm; median: 3.2 cm) from 2007 to 2010 were identified. Tumor size, estimated blood loss, and ischemia time all significantly differed (p < 0.0001) between groups; patient age, body mass index (BMI), and operative time were comparable. When stratified by CCS, minor and major complication rates for all patients were 26.7% and 11.5%, respectively. Minor complication rates were comparable (26.6 vs 24.9 vs 32.8%; p = 0.45), whereas major complication rates differed (6.4 vs 11.1 vs 21.9%; p = 0.009) among tumor complexity groups. Controlling for age, gender, BMI, type of surgical approach, operative duration, and tumor complexity, prolonged operative time (odds ratio [OR]: 1.01; confidence interval [CI], 1.0-1.02) and high tumor complexity (OR: 5.4; CI, 1.2-24.2) were associated with the postoperative development of a major complication. Lack of external validation is a limitation of this study.

Conclusions

Increasing tumor complexity is associated with the development of major complications after PN. This association should be validated externally and integrated into the decision-making process when counseling patients with complex renal tumors.     

Efficacy and safety of once-daily dosing of udenafil in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial

Background

A once-daily dosing regimen with a phosphodiesterase type 5 inhibitor is needed for the treatment of erectile dysfunction (ED), in part because of the behavioral complexities associated with sexual intimacy. Many patients prefer spontaneous rather than scheduled sexual activities or they anticipate frequent sexual encounters. The pharmacokinetic profiles of udenafil with a time of maximal concentration of 1.0-1.5 h and a terminal half-life of 11-13 h make udenafil a good candidate for once-daily dosing.

Objective

To evaluate the efficacy and safety of once-daily dosing of udenafil in the treatment of ED.

Design, setting, and participants

This multicenter randomized double-blind, placebo-controlled, fix-dosed clinical trial involved 237 patients with ED. The subjects, who were treated with placebo or udenafil (25 mg, 50 mg, or 75 mg) once daily for 12 wk, were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ) during the study.

Measurements

The primary outcome parameter was the change from baseline for the IIEF erectile function domain (EFD) score. The secondary outcome parameters were SEP questions 2 and 3, the shift to normal rate (EFD ≥26), and the response to the GAQ.

Results and limitations

Compared with placebo, patients who took 50 mg or 75 mg of udenafil had a significantly improved IIEF-EFD score. Similar results were observed in comparing questions 2 and 3 in the SEP diary and the GAQ. Flushing was the most common treatment-related adverse event, which was transient and mild to moderate in severity.

Conclusions

Udenafil significantly improved erectile function among ED patients when administered in doses of 50 mg or 75 mg once daily for 12 wk. Daily administration of udenafil (50 mg) may be another treatment option for ED.     

A double blind, randomised trial to compare the analgesic effect of oral premedication with paracetamol, diclofenac, or diclofenac and paracetamol, on postoperative pain following surgical suction termination of pregnancy

Objectives:

The aim of this study was to determine whether a combination of paracetamol and diclofenac provided a more effective analgesic premedication than paracetamol, or diclofenac alone for the treatment of postoperative pain following surgical suction termination of early pregnancy.

Methods:

A double blind, prospective trial, involving 60 patients randomized to receive either paracetamol (1 g) and placebo, diclofenac (50 mg) and placebo, or diclofenac (50 mg) and paracetamol (1 g) orally, prior to surgical termination of pregnancy. Intraoperative management was standardized. Peak pain was the primary end point. Pain scores were recorded immediately postoperatively, and at 2 and 4 h. Secondary end points were nausea, sedation, intraoperative blood loss, supplementary postoperative analgesic use, and delayed hospital discharge.

Results:

There was no statistically significant difference in peak pain between the three groups (P = 0.6).

Discussion:

The co-administration of prophylactic oral analgesic premedication with diclofenac and paracetamol did not result in a reduction in pain scores when compared to either diclofenac or paracetamol administered alone.     

Identifying predictors of early non-recovery in a compensation setting: The Whiplash Outcome Study

Context

People with Whiplash Associated Disorder (WAD) often experience pain and disability for extended periods of time. A large proportion of these people will seek treatment through a compensation process. Rarely is data related to people's health collected within the compensation process making it difficult to identify those that are at risk of delayed recovery and appropriately direct interventions.

Study objective

To compare people with WAD who have recovered with those that have not, within 3 months of injury and identify potential predictors of poorer health and non-recovery to inform claim screening processes.

Study design

Cross-sectional analysis of a cohort study.

Participants

People who sustained a WAD and claimed compensation within an Australian Motor Accidents Compensation Scheme between November 2007 and June 2009.

Measure of recovery

Functional Rating Index (FRI) score (≤25).

Health outcome measures

Short Form 36 (SF36), FRI, and the Pain Catastrophising Scale (PCS).

Methods

246 people who had lodged a claim for compensation were enrolled in the Whiplash Outcome Study within 3 months of sustaining a WAD injury. Participants were assigned to a recovered or non-recovered group and analysed for differences between the two groups. Multiple linear regression models were used to identify potential predictors of poorer health and non-recovery.

Results

Overall 23% of the study population had recovered within 3 months of sustaining a WAD, whilst only 9% had finalised their insurance claim. The recovered group had significantly better scores on all health outcome measures; SF36 Physical Component Score, SF36 Mental Component Score and the PCS (p < 0.001). The significant independent predictors of poorer health and non-recovery were helplessness (p < 0.001), older age (p < 0.001) and pre-injury work status being affected (p < 0.001) (r² = .624). Regardless of the health outcome measure used, helplessness was significantly associated with poorer reported health.

Conclusion

Including additional information at claim notification, specifically the PCS and information on the effect the injury has on the working population could significantly improve claim screening processes, identifying those with poorer health and risk of non-recovery.     

Health and cost consequences of surgical versus conservative treatment for a comminuted proximal humeral fracture in elderly patients

Objective

This study aims to evaluate the costs and health outcome for surgical and conservative treatment of displaced proximal humeral fractures.

Design

This study is a randomised controlled trial.

Participants

This study included 50 patients aged 60 or older admitted to hospital with a severely displaced three- or four-part fracture.

Interventions

The patients were treated surgically with an angular stable interlocking implant (25 patients) or conservative treatment (25 patients).

Main outcome measure

The outcomes measured included quality-adjusted life years (QALYs) and societal costs.

Results

At 12 months’ follow-up, the mean difference in the number of QALYs was 0.027 (95% confidence interval (CI) = −0.025, 0.078) while the mean difference in total health-care costs was €597 in favour of surgery (95% CI = −5291, 3777).

Conclusion

There was no significant difference in QALYs or costs between surgical and conservative treatment of severe displaced proximal humeral fractures.     

Is the red-yellow-black scheme suitable to classify donor site wounds? An inter-observer analysis

Background

The red-yellow-black-scheme (RYB) is a well-known and validated scheme to classify chronic and acute wounds, based on wound color and moistness. We investigated whether this RYB-scheme is also useful to classify donor site wounds uniformly (DSW).

Methods

Twenty-three digital photographs of DSWs in various stages of wound healing were presented to internationally renowned wound scientists (n = 11), surgical doctors (n = 31), specialized wound nurses (n = 55), and surgical nurses (n = 28). These observers classified the color and moistness of the wound according to the RYB-scheme, yielding seven wound categories. Inter-observer agreement (IOA) was expressed as a kappa (κ) value.

Results

IOA's among specialized wound nurses were moderate when based on wound color and moistness (κ = 0.41; 95% CI 0.33-0.49), wound color only (κ = 0.41; 95% CI 0.29-0.53), or moistness only (κ = 0.54; 95% CI 0.45-0.64). However, these IOA's tended to be better than those among the scientists, doctors and nurses. Scientists showed the lowest agreement (k-values between 0.17 and 0.25). Doctors scored slightly better than nurses.

Conclusion

Clinicians and scientists have difficulty with classifying DSWs by means of the RYB-scheme. Therefore, this scheme does not appear useful to classify donor site wounds in a uniform manner.     

The outcome of patients treated with sunitinib prior to planned nephrectomy in metastatic clear cell renal cancer

Background

The role of cytoreductive nephrectomy in metastatic clear cell renal cell carcinoma (ccRCC) is controversial.

Objective

To determine the outcome of patients with metastatic ccRCC who receive sunitinib prior to planned nephrectomy.

Design, setting, and participants

The study combined the data from two prospective phase 2 studies that assessed upfront sunitinib (12-16 wk) prior to nephrectomy in previously untreated patients with metastatic renal cell carcinoma (RCC). Sunitinib was discontinued during the perioperative period (median: 29 d).

Intervention

Sunitinib 50 mg in six weekly cycles (4 wk on, 2 wk off).

Measurements

Progression-free (PFS) and overall survival (OS) using the Kaplan-Meier method.

Results and limitations

Twenty-one patients (32%) had Memorial Sloan-Kettering Cancer Centre (MSKCC) poor-risk disease; 45 (68%) had intermediate-risk disease. Nephrectomy was not performed in 19 (29%), most commonly due to disease progression (n = 12). The PFS for the cohort was 6.3 mo (95% confidence interval [CI], 5.1-8.5). Seventeen (36%) patients progressed during the treatment break, 13 (76%) of whom stabilised upon reinitiating of sunitinib. The OS for the cohort was 15.2 mo (95% CI, 10.3-NA). The OS for the intermediate MSKCC risk group was significantly longer than that for the poor-risk group (26.0 mo [95% CI, 13.6-NA] and 9.0 mo [95% CI, 5.8-20.5], respectively; p < 0.01). In multivariate analysis, progression of disease prior to planned nephrectomy (hazard ratio [HR]: 5.34; 95% CI, 3.17-13.27), high Fuhrman grade (HR 3.27; 95% CI, 1.38-7.72), and MSKCC poor risk at diagnosis (HR 4.75; 95% CI, 2.05-11.02) were associated with short survival (p < 0.01). However, in the absence of randomised studies it is not possible to determine if this approach is beneficial.

Conclusions

Upfront sunitinib prior to planned nephrectomy in intermediate-risk disease is associated with a median survival of >2 yr despite frequent progression during treatment break. Progression in metastatic sites prior to planned surgery and MSKCC poor-risk disease was associated with a poor outcome.