The impact of long-term haemofiltration (continuous veno-venous haemofiltration) on cell-mediated immunity during endotoxaemia

BACKGROUND: Increased survival with high-volume continuous veno-venous haemofiltration (CVVH) has been demonstrated in critically ill patients. This may be the result of intensified blood purification or an effect on the immune system. We hypothesized that CVVH modifies the cell-mediated immunity. We investigated the effect of high-volume CVVH for 24 h on the cell-mediated immunity following endotoxin infusion. METHODS: Thirty pigs were divided into three groups. Ten pigs received 30 microg/kg of Escherichia coli endotoxin. These pigs were treated with CVVH (replacement 35 ml/kg/h) over the following 24 h. Ten pigs received the same bolus of endotoxin and ten pigs served as a control group. The adhesion molecules CD18, CD44 and CD62L and the ability to respond with an oxidative burst were measured. The number of neutrophils was counted in blood and lung tissue. The lymphoproliferative response and cytokines interleukin-6 and interleukin-10 were measured. RESULTS: The infusion of endotoxin was followed by initial granulocytopenia and, later, granulocytosis, activation of CD18 and CD62L, and increased oxidative burst. The cytokine level was increased. CVVH had no effect on the adhesion molecules or cytokine level and did not reduce the number of granulocytes in the lung significantly. CVVH, however, reduced the oxidative burst activity of neutrophils after 2 h of treatment. CONCLUSION: In the first few hours after endotoxaemia, high-volume CVVH reduced the oxidative burst activity of neutrophils. However, in the long term, CVVH was unable to modify the endotoxin-induced changes in cell-mediated immunity.     

Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Erectile dysfunction (ED) is a chronic disease; however, therapy is currently administered as needed with oral phosphodiesterase 5 (PDE5) inhibitors like tadalafil. Because the 17.5-h half-life of tadalafil enables therapeutic plasma levels to be sustained with daily administration, tadalafil is a good candidate for once daily dosing therapy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week study enrolled 268 men 1:2:2 to placebo, tadalafil 5mg, and tadalafil 10mg taken once daily. Primary efficacy measures included changes in the International Index of Erectile Function Erectile Function domain (IIEF EF), Sexual Encounter Profile diary Questions 2 (SEP2: successful penetration), and 3 (SEP3: successful completion of intercourse), and tolerability. Secondary measures included percentage of patients at endpoint who reported improved erectile function (EF), and percentage who reported "no ED" (IIEF EF score 26-30). RESULTS: For patients who took placebo, tadalafil 5mg, and tadalafil 10mg, changes from baseline to endpoint were, respectively, 0.9, 9.7, and 9.4 for IIEF EF; 11.2, 36.5, and 39.4 for SEP2; and 13.2, 45.5, and 50.1 for SEP3. At endpoint, 28.3%, 84.5%, and 84.6% reported improved erections, and 8.3%, 51.5%, and 50.5% reported "no ED," respectively. All comparisons between tadalafil and placebo were significant (p<0.001). Adverse events that occurred in at least 5% of patients were dyspepsia, headache, back pain, upper abdominal pain, and myalgia; nine patients (3.4%) discontinued because of adverse events. CONCLUSIONS: Once-a-day tadalafil 5mg or 10mg was well tolerated and significantly improved EF in men with ED.     

Effects of continuous haemofiltration vs intermittent haemodialysis on systemic haemodynamics and splanchnic regional perfusion in septic shock patients: a prospective, randomized clinical trial.

BACKGROUND: Parameters of splanchnic regional perfusion, like intramucosal pH (pHi) and pCO(2) (pCO(2)i), may predict outcome in septic shock patients. Continuous venovenous haemofiltration (CVVH) has been considered beneficial in haemodynamically unstable septic shock patients. In a prospective, randomized, clinical study, we investigated whether CVVH, in comparison to intermittent haemodialysis (IHD), is able to improve splanchnic regional perfusion in critically ill patients. METHODS: Thirty septic shock patients with acute renal failure were randomized to either CVVH (n=20) or IHD (n=10) groups for renal replacement therapy. Patient characteristics at baseline were not different in terms of severity of illness (APACHE II scores), haemodynamics, and pHi/pCO(2)i values. Systemic haemodynamics, oxygen transport variables, and splanchnic regional perfusion parameters were measured at 0.5, 2, 4 and 24 h after initiation of renal replacement therapy. There were no major changes in vasopressor support throughout the 24-h study period. RESULTS: In contrast to IHD, CVVH caused a decrease in heart rate (-3+/-11 vs +9+/-8/min, P<0.01) and an increase in systolic blood pressure (+12+/-1 vs -5+/-17 mmHg, P<0.05) after 2 h. After 24 h, increased systemic vascular resistance was found in the CVVH group in comparison with the IHD group (+312+/-755 vs -29+/-89 dyne/cm(5), P<0.05) and was accompanied by a decrease in cardiac output (-1.54+/-1.4 vs -0.25+/-0.9 l/min, P<0.01). However pHi values remained constant throughout the 24-h study period in both groups and were not different between the groups (CVVH 7.19+/-0.1 vs IHD 7.19+/-0.1, n.s.) as did the pCO(2)i values (CVVH +7+/-17 vs IHD 0+/-15 mmHg, n.s.) and pCO(2) gap values (CVVH +6+/-15 vs IHD +5+/-12 mmHg, n.s.). CONCLUSIONS: Despite different changes of systemic haemodynamics between CVVH and IHD, CVVH did not improve parameters of splanchnic regional perfusion like pHi, pCO(2)i or pCO(2) gap in septic shock patients.     

Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo).

BACKGROUND: Darbepoetin alfa is an erythropoietic agent with a 3-fold longer elimination half-life than recombinant human erythropoietin (rHuEpo), which allows less frequent dosing. This study investigated the safety and efficacy of darbepoetin alfa for treating anaemia in dialysis patients, using a dosing regimen that was independent of the patient's body weight (unit dosing). METHODS: Dialysis patients (n=341) maintained on rHuEpo treatment (alfa or beta) were switched to darbepoetin alfa at a reduced dosing frequency, but by the same route of administration [intravenous (i.v.) or subcutaneous (s.c.)]. Patients receiving rHuEpo two or three times weekly changed to once-weekly darbepoetin alfa, and those receiving rHuEpo once weekly changed to once every other week darbepoetin alfa. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations within -1.0 and +1.5 g/dl of the individual mean baseline haemoglobin and between 10 and 13 g/dl for 24 weeks. RESULTS: Mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was 0.13 g/dl (95% CI, 0.01, 0.25), which was not clinically relevant. An analysis by route of administration revealed that mean haemoglobin concentrations had increased by 0.58 g/dl (95% CI, 0.33, 0.82) in patients receiving i.v. darbepoetin alfa, and previously treated with i.v. rHuEpo, while remaining unchanged in s.c. patients (0.00 g/dl; 95% CI, -0.13, 0.13) previously treated by s.c. rHuEpo. In addition, there was a statistically significant decrease in mean weekly i.v. darbepoetin alfa dose requirements from 25.2 microg/week at baseline to 21.5 microg/week (P=0.004) during the evaluation period (-17.3%). Subcutaneous weekly dosage requirements increased slightly during the study period (20.8 to 22.7 microg/week; P=0.014). An i.v./s.c. dose ratio of 0.95 (95% CI, 0.78, 1.14) at evaluation confirms previous findings that dose requirements by the i.v. and s.c. routes were not different in patients treated with darbepoetin alfa. Haemoglobin concentrations were also effectively maintained in patients who received darbepoetin alfa once weekly and once every other week. Darbepoetin alfa was well tolerated. CONCLUSIONS: The treatment of renal anaemia in dialysis patients with unit doses of darbepoetin alfa effectively and safely maintains target haemoglobin concentrations with less frequent dosing. Dose requirements for darbepoetin alfa following i.v. and s.c. administration were not different. The results of this study demonstrate that darbepoetin alfa administered i.v. once weekly, or once every other week is an effective treatment regimen for haemodialysis patients with renal anaemia.     

Sperm suppression with monthly injections of medroxyprogesterone acetate combined with testosterone enanthate at a high dose (500 mg)

The combination of an initial injection of 1000 mg of depot medroxyprogesterone acetate and 500 mg of testosterone enanthate, followed by monthly administration of 150 mg and 500 mg of the same drugs, was tested in 10 healthy males aged 28 through 39, with pre-treatment sperm counts of 50 times 10⁶/ml or more. Eight of the subjects achieved azoospermia, and the sperm counts of the other two declined 0.09 and 5 million/ml. This last subject was highly refractory to treatment as his sperm density recovered to 27 million sperm/ml at the 6th month of continuous therapy. FSH was severely depressed during the entire treatment period. LH fell to 30–40% of normal values in the first two months and then showed a slow recovery during maintenance treatment. Testosterone measured one month after each injection was between 10 and 30% of pre-treatment values. Three of the subjects had increased libido and potency, none had decreased sexual drive or potency. All subjects gained weight with the average gain being 6 kg. The increase in the dose of testosterone enanthate to 500 mg/ng did not improve the results as compared to previous trials using lower doses of TE.     

Single daily overnight (12-h dwell) use of 7.5% glucose polymer (Mw 18700; Mn 7300) +0.35% glucose solution: a 3-month study

The osmotic effectiveness of an isosmolar glucose polymer (GP)solution during long-dwell (8–12 h) peritoneal dialysishas been demonstrated. The absorption of GP, though only a fractionof currently used glucose, is usually accompanied by the systemicaccumulation of its breakdown product, maltose. The long-termconsequences of maltose accumulation remain unknown. We studied the accumulation pattern of GP fractions, changesin serum electrolytes, osmolality, and adverse reaction profileover a 3-month period, using a daily regime of an overnightexchange of 7.5% GP±0.35% glucose solution with threedaytime exchanges of 1.36% glucose in five non-diabetic CAPDpatients. The GP solution (299 ±0.7 mOsm/kg) produced mean dailyovernight UF of 589 ml and maintained stable serum biochemistry.The mean serum maltose level increased from a preanalysis valueof 0.03 ±008 g/1 to a steady-state level of 1.1 ±0.14g/1 within 2 weeks and remained stable throughout the study.This did not influence serum osmolality or sodium and producedno significant adverse effects. Once-daily overnight use of an isosmolar GP solution is safeand effective. The accumulation of maltose reaches steady-statelevels quickly and produces no adverse toxic effects in theshort term. Further long-term studies are planned.     

The pharmacokinetics and analgesic efficacy of larger dose rectal acetaminophen (40 mg/kg) in adults: a double-blinded, randomized study

Analgesic acetaminophen plasma concentrations are not known. We investigated in a randomized, double-blinded study the pharmacokinetics and analgesic efficacy of small- (AS; 20 mg. kg(-1)) and larger- (AL; 40 mg/kg) dose rectal acetaminophen and compared it with the combination (C) of rectal diclofenac (100 mg) and acetaminophen (20 mg/kg) in 65 women undergoing hysterectomy. Suppositories were administered after the induction of a standardized general anesthesia. Pain (measured by using a 10-cm visual analog scale) and morphine consumption (patient-controlled analgesia) were repeatedly assessed for 24 h. Acetaminophen plasma concentrations were measured by using a fluorescence polarization immunoassay. Antipyretic plasma concentrations (10-20 mg/L) after 40 mg/kg acetaminophen were not associated with improved analgesia or decreased opioid requirements; 20 mg/kg acetaminophen produced subtherapeutic plasma levels (<10 mg/L). Maximal plasma concentrations of 17.2 and 10.4 mg/L (P < 0.01, analysis of variance) were achieved after 4.2 and 3.6 h for the AL and AS groups, respectively. The only difference in clinical outcome was lower visual analog scale scores after acetaminophen/diclofenac (C 2.0 versus AS 3.2 and AL 3.4) 4 h after the induction (P < 0.05, analysis of variance). Acetaminophen pharmacokinetics in adults were similar to those observed in children. Analgesic plasma concentrations are likely to be higher than antipyretic plasma levels, which were only attained after twice the recommended rectal dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis. IMPLICATIONS: Acetaminophen pharmacokinetics were comparable in adults and children. Plasma concentrations known to reduce fever did not produce better pain relief and were only achieved after twice the conventional dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.     

Ganciclovir exposure under a 450 mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study

Manuel O, Pascual M, Perrottet N, Lamoth F, Venetz J‐P, Decosterd LA, Buclin T, Meylan PR. Ganciclovir exposure under a 450 mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study.
Clin Transplant 2010: 24: 794–800. © 2010 John Wiley & Sons A/S. Abstract: This prospective study aimed at determining the ganciclovir exposure observed under a daily dosage of 450 mg valganciclovir routinely applied to kidney transplant recipients with a GFR above 25 mL/min at risk for cytomegalovirus (CMV) disease. Ganciclovir levels at trough (C_trough) and at peak (C_{3 h}) were measured monthly. Ganciclovir exposure (area under the curve [AUC_0–24]) was estimated using Bayesian non‐linear mixed‐effect modeling (NONMEM). Thirty‐six patients received 450 mg of valganciclovir daily for three months. Median ganciclovir C_{3 h} was 3.9 mg/L (range: 1.3–7.1), and C_trough was 0.4 mg/L (range 0.1–2.7). Median AUC_0–24 of ganciclovir was 59.3 mg h/L (39.0–85.3) in patients with GFR_MDRD 26–39 mL/min, 35.8 mg h/L (24.9–55.8) in patients with GFR_MDRD 40–59 mL/min, and 29.6 mg h/L (22.0–43.2) in patients with GFR_MDRD ≥ 60 mL/min. No major differences in adverse events according to ganciclovir exposure were observed. CMV viremia was not detected during prophylaxis. After discontinuing prophylaxis, CMV viremia was seen in 8/36 patients (22%), and 4/36 patients (11%) developed CMV disease. Ganciclovir exposure after administration of valganciclovir 450 mg daily in recipients with GFR ≥60 mL/min was comparable to those previously reported with oral ganciclovir. A routine daily dose of 450 mg valganciclovir appears to be acceptable for CMV prophylaxis in most kidney transplant recipients.     

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: A prospective randomized trial

PURPOSE: Daily divided dose cisplatin (DDD-P) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected colorectal cancer as the adjuvant therapy. METHODS: One hundred and eighty-eight stage II or III colorectal cancer patients were enrolled. Patients were randomly assigned to receive DDD-FP (5-FU, 320 mg/ m(2), daily for 21 days; CDDP, 3.5 mg/m(2) daily for 21 days) followed by oral 5-FU (200 mg/body daily for 2 years) (DDD-FP arm) or oral 5-FU therapy (200 mg/ body daily for 2 years) exclusively (oral 5-FU arm). RESULTS: The 5-year disease-free survival (DFS) rates and the overall survival (OS) rates indicated no significant difference between the two arms. By stratified analysis, in the colon cancer patients, the DFS and the OS for the DDD-FP arm were significantly increased: 93.5% and 95.7% in the DDD-FP arm as compared with 76.9% and 82.2% in the oral 5-FU arm (P = 0.024 and P = 0.038). Regarding adverse effects, grade 3-4 toxicities were not significant in two arms. CONCLUSIONS: DDD-FP followed by oral 5-FU therapy suggested a feasible regimen for patients with resected colon cancer as the adjuvant therapy.     

An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study

OBJECTIVES: Assess the effects on spermatogenesis of daily tadalafil 20mg over three spermatogenesis cycles in men >or= 45 yr. METHODS: In this double-blind, placebo-controlled, noninferiority study, healthy men (or with mild erectile dysfunction) were randomized to receive tadalafil 20mg (n=125) or placebo (n=128) for 9 mo followed by a 6-mo, treatment-free period. Semen and serum samples were provided at baseline and every 10-12 wk. The primary outcome was the proportion of subjects with >or= 50% reduction in sperm concentration at end point. Secondary outcomes included sperm concentration, number per ejaculate, motility and morphology; serum concentrations of testosterone, luteinizing and follicle-stimulating hormones; and tolerability. RESULTS: Of 253 men enrolled, 191 (75%) completed treatment phase: 2 of 96 (2.1%, placebo) and 12 of 95 (12.6%, tadalafil) subjects had >or= 50% reduction in sperm concentration. Tadalafil was noninferior to placebo because the upper 95% confidence interval for the difference in proportions of tadalafil and placebo subjects with a >or= 50% reduction in sperm concentration was 17.5%, significantly less than the prespecified noninferiority margin of 20% (p=0.015). Ninety-four percent (179 of 191) of men completed the 6-mo, treatment-free period: Baseline sperm concentration levels were restored in 8 of 12 (tadalafil) and 1 of 2 (placebo) men. There were no significant differences between groups in secondary end points. Common treatment-emergent adverse events were headache, back pain, dyspepsia, gastroesophageal reflux disease, and myalgia. Twelve (9.6%) tadalafil and seven (5.5%) placebo subjects discontinued because of adverse events. CONCLUSIONS: This study demonstrated no deleterious effects of 9 mo of daily tadalafil 20mg on spermatogenesis or hormones related to testicular function in men >or= 45 yr.     

The new proximal femoral nail antirotation (PFNA) in daily practice: results of a multicentre clinical study

The treatment of unstable trochanteric femoral fractures is still challenging. The ideal implant should be easy to handle, allow for immediate full weight-bearing postoperatively and should have sufficient purchase in the femoral head/neck-fragment to limit cut-outs due to varus-deviation and rotation. The proximal femoral nail antirotation (PFNA), designed by AO, is an intramedullary device with a helical blade rather than a screw for better purchase in the femoral head and was tested in a clinical study. Consecutive patients with unstable trochanteric fractures (AO-classification 31.A.2 and A.3 only) were included and followed for 1 year. Primary objectives were assessment of operative and postoperative complications, whereas secondary objectives included surgical details, general complications and final outcome measurements. In 11 European clinics, 315 patients were included and treated with a PFNA. Almost all fractures healed within 6 months. Fifty-six percent of the patients regained the pre-trauma mobility and 18% died within the follow-up period. Forty-six implant-related complications--leading to 28 unplanned re-operations--were recorded, with four acetabular penetrations (three of which were after a new fall on that hip) and seven ipsilateral femoral shaft fractures as the most serious ones. As the joint-penetrations did not resemble the cut-out seen with other implants it is concluded that the PFNA--due to its helical blade--possibly limits the effects of early rotation of the head/neck-fragment in unstable trochanteric fractures and therefore seems currently to be the optimal implant for the treatment of these fractures especially in osteoporotic bone.     

The effect of reduction of the peripheral fat content by liposuction-assisted lipectomy (SAL) on serum leptin levels in the postoperative period: a prospective study

The purpose of this study was to investigate the relationship between a decrease in the peripheral fat content by suction-assisted lipectomy (SAL) and serum leptin levels. Twenty-two healthy females who underwent SAL for aesthetic reasons participated in the study. The data included height, weight, dietary habits, and leptin levels before surgery and at 1 and 6 weeks postoperatively. The aspirate ranged between 1000 and 6000 ml, with an average of 2700 ml. Thirteen patients with an aspirate of over 2700 ml all experienced an immediate postoperative decrease in appetite which returned gradually by 12 to 17 days postoperatively. They lost an average of 7% of the total body weight at 6 weeks. The leptin levels 1 week postoperatively were significantly lower than the preoperative levels (p < 0.01); at 6 weeks the decrease in leptin level was not statistically significant. In conclusion, a reduction of the peripheral fat content of more than 2700 ml by SAL has an immediate effect on leptin levels that lasts at least 1 week and correlates with voluntary changes in energy intake.     

A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer

PURPOSE: The safety, efficacy and pharmacokinetics of LA-2585, a new 6-month subcutaneous depot of leuprolide acetate (Atrix Laboratories, Fort Collins, Colorado) were investigated in patients with prostate cancer. MATERIALS AND METHODS: In this 12-month, open label, multicenter study 111 patients with adenocarcinoma of the prostate were administered 45.0 mg LA-2585 subcutaneously once every 6 months. The primary efficacy parameter was serum testosterone 50 ng/dl or less. Leuprolide acetate pharmacokinetics were analyzed in a subset of 28 patients. RESULTS: Of the 111 enrolled patients 103 (93%) completed the 12-month study. Eight patients withdrew due to nonmedical reasons in 1, disease progression in 5 and cardiovascular disease in 2. By day 28, 108 of the 109 remaining patients (99%) achieved testosterone suppression, while 1 who never attained suppression was withdrawn at day 85. Mean time to castrate suppression was 21.2 days (median 21). At study completion 102 of 103 patients (99%) were below medical castrate testosterone levels of 50 ng/dl (mean +/- SE 12.3 +/- 2.1 ng/dl) with 91 of 103 (88%) at less than 20 ng/dl. Mean luteinizing hormone decreased from 6.98 +/- 0.48 mIU/ml at baseline to 0.23 +/- 0.14 mIU/ml at month 12. Luteinizing hormone was consistently below 1 mIU/ml. Mean prostate specific antigen decreased 97% from 39.8 +/- 21.5 ng/ml at baseline to 1.2 +/- 0.3 ng/ml at 12 months. No clinically significant flare reactions were observed. The most common treatment related adverse event was mild to moderate hot flashes. CONCLUSIONS: LA-2585 (45.0 mg depot) consistently produced and maintained safe and effective serum testosterone suppression with total serum testosterone well below the medical castrate level of less than 50 ng/dl.     

Bilateral Lower Extremity Sequential Compression Devices (SCDs): A Novel Approach to the Management of Intra-Dialytic Hypotension in the Outpatient Setting—Report of a Case Series

Intra-dialytic hypotension (IDH) affects as many as 15–50% of patients during hemodialysis. Several treatment approaches and preventative methods are available. These therapeutic options are often ineffective and cumbersome, and some of the causative factors such as poor cardiac reserve are commonly not amenable to any therapy. Enhanced external counter pulsation (EECP) is increasingly being utilized by cardiology services as an adjunct to the long-term management of chronic congestive heart failure as well as in the management of otherwise refractory angina. EECP works by mechanistically improving venous return, enhancing peripheral resistance, and ultimately improving the cardiac index. We speculated that bilateral lower extremity sequential compression devices (SCDs), commonly used in the inpatient setting for DVT prophylaxis, could indeed serve as mini-EECP devices. We carried out an outpatient pilot study of its use to prevent IDH in three patients who otherwise had failed other treatment approaches. The SCDs were effective, convenient, and safe. We were able to achieve ultrafiltration (UF) goals of 1–3 kg during hemodialysis sessions in all three patients, consistently, for months, a feat that was not possible previously. This novel modality of managing IDH is complementary to other standard therapies. Larger multi-center studies are warranted.     

Accuracy of high resolution (1.5 tesla) pelvic phased array magnetic resonance imaging (MRI) in staging prostate cancer in candidates for radical prostatectomy: Results from a prospective study

ObjectiveTo evaluate the role of pelvic phased array MRI in staging prostate cancer (CaP).Materials and methodsWe prospectively collected data over 12 months on CaP patients who underwent preoperative MR imaging with a pelvic phased array before radical prostatectomy. MR images were analyzed prospectively by 2 radiologists. MR imaging findings were then correlated with pathologic findings.ResultsOverall, 101 patients were included with a mean PSA level of 8 (range 1.8–30). Reader 1 (AUC 0.895, 95% CI 0.791–0.999) had a higher performance than reader 2 (AUC 0.687, 95% CI, 0.555–0.819) and than DRE (AUC 0.728, 95% CI, 0.599–0.857) in discriminating T2 from T3 CaP (P = 0.01). The κ-index of inter-observer agreement was 0.56. A model that combines MRI findings, DRE, PSA, and Gleason score was the most competitive for staging (AUC 0.895, 95% CI, 0.791–0.999). For the multivariate analysis, 3 criteria were significantly associated with extracapsular extension: asymmetry of the neuro-vascular bundles (P = 0.001), asymmetric enhancement of neurovascular bundles (P = 0.02), and bulging of the capsule (P = 0.0003).ConclusionPelvic phased array MRI presented satisfying results in its ability to adequately stage CaP and notably in detecting the extracapsular extension of tumors. It is likely to provide reliable information but rather in the hands of an experienced radiologist.     

The need for a transparent, ethical, and successful relationship between academic scientists and the pharmaceutical industry: a view of the Group for the Respect of Ethics and Excellence in Science (GREES)

Summary

This paper provides recommendations for fair and unbiased relationship between academic scientists and the pharmaceutical industry.

Introduction

Real or perceived problems in the relationship between academics and the industry have been the subject of much recent debate. It has been suggested that academic clinicians should sever all links with the industry—a view that is rarely challenged.

Methods

Academic experts and members of the pharmaceutical industry were invited to an expert consensus meeting to debate this topic. This meeting was organized by the Group for the Respect of Ethics and Excellence in Science. Conflict of interest, competing interest, right and duties of academic scientist, authorship, and staff and student education were discussed.

Results

Guidelines for a transparent, ethical, strong, and successful partnership between the academic scientist and the pharmaceutical industry have been provided.

Conclusions

The Group support interactions between the industry and clinicians provided that it is transparent and ethical.