Doxycycline compared with prednisolone therapy for patients with bullous pemphigoid: cost-effectiveness analysis of the BLISTER trial.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering skin disorder associated with significant morbidity and mortality. Doxycycline and prednisolone to treat bullous pemphigoid were compared within a randomized controlled trial (RCT). OBJECTIVES: To compare the cost-effectiveness of doxycycline-initiated and prednisolone-initiated treatment for patients with BP. METHODS: Quality-of-life (EuroQoL-5D-3L) and resource data were collected as part of the BLISTER trial: a multicentre, parallel-group, investigator-blinded RCT. Within-trial analysis was performed using bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, informing a probabilistic assessment of incremental treatment cost-effectiveness from a health service perspective. RESULTS: In the base case, there was no robust difference in costs or QALYs per patient at 1 year comparing doxycycline- with prednisolone-initiated therapy [net cost £959, 95% confidence interval (CI) -£24 to £1941; net QALYs -0·024, 95% CI -0·088 to 0·041]. However, the findings varied by baseline blister severity. For patients with mild or moderate blistering (≤ 30 blisters) net costs and outcomes were similar. For patients with severe blistering (> 30 blisters) net costs were higher (£2558, 95% CI -£82 to £5198) and quality of life poorer (-0·090 QALYs, 95% CI -0·22 to 0·042) for patients starting on doxycycline. The probability that doxycycline would be cost-effective for those with severe pemphigoid was 1·5% at a willingness to pay of £20 000 per QALY. CONCLUSIONS: Consistently with the clinical findings of the BLISTER trial, patients with mild or moderate blistering should receive treatment guided by the safety and effectiveness of the drugs and patient preference - neither strategy is clearly a preferred use of National Health Service resources. However, prednisolone-initiated treatment may be more cost-effective for patients with severe blistering.

Fibrolamellar variant of hepatocellular carcinoma does not have a better survival than conventional hepatocellular carcinoma--results and treatment recommendations from the Childhood Liver Tumour Strategy Group (SIOPEL) experience.

PURPOSE: Fibrolamellar hepatocellular carcinoma (FL-HCC) and conventional hepatocellular carcinoma (HCC) cases in two consecutive paediatric HCC trials were analysed to compare outcome and derive treatment implications. PATIENTS AND METHODS: Data of 24 FL-HCC (24% PRETEXT IV) and 38 HCC (42% PRETEXT IV) cases from SIOPEL-2 and -3 (1995-1998, 1998-2006) were analysed. Patients were treated according to SIOPEL-2 and -3 high-risk protocol (carboplatin+doxorubicin alternating with cisplatin; seven preoperative, three postoperative cycles) or with primary surgery followed by chemotherapy as indicated. RESULTS: Thirteen of 24 FL-HCC (54%) and 32/38 HCC (84%) were initially treated with chemotherapy. Eight FL-HCC (33%) and five HCC patients (13%) had primary surgery. Partial response was observed in 31% of FL-HCC versus 53% of HCC patients (p=0.17). Complete resection was achieved in ten FL-HCC and seven HCC patients (p=0.08). Three-year event free survival (EFS) was 22% for FL-HCC versus 28% for HCC. Overall survival (OS) was not significantly different at 3 years follow up (42% for FL-HCC versus 33% for HCC, p=0.24). EFS/OS Kaplan-Meier curves did not differ significantly, with median follow up of 43 (FL-HCC) and 60 (HCC) months. No significant correlation was found between potential prognostic factors and OS. In the entire cohort nine out of 23 (39%) patients with complete resection or orthotopic liver transplantation versus 34/39 (87%) without successful surgical treatment, died. CONCLUSIONS: Long-term OS in FL-HCC and HCC is similar. With low response rates, complete resection remains the treatment of choice.

Overall survival and development of stage IV chronic kidney disease in patients undergoing partial and radical nephrectomy for benign renal tumors.

BACKGROUND: Although partial nephrectomy (PN) has been associated with improved renal function compared with radical nephrectomy (RN) for renal cell carcinoma, the impact on overall survival (OS) remains controversial. OBJECTIVE: To evaluate comparative OS and renal function in patients following PN and RN for a renal mass where malignancy was not a confounding factor. DESIGN, SETTING, AND PARTICIPANTS: Using the Mayo Clinic Nephrectomy Registry, we retrospectively identified 442 patients with unilateral sporadic benign renal masses treated surgically with PN or RN between 1980 and 2008. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome measures were OS and the incidence of new-onset stage IV chronic kidney disease (CKD), determined using the Kaplan-Meier method. Cox models were used to test the association of nephrectomy type with these outcomes. RESULTS AND LIMITATIONS: Overall, 206 and 236 patients with benign renal masses were surgically treated with RN and PN, respectively. Patients who underwent RN were older (median age: 67 vs 64 yr; p=0.02) and had larger tumors (median size: 5.0 vs 2.7 cm; p<0.001). Median follow-up for patients still alive at last follow-up was 8.3 yr (range: 0.1-27.9 yr). Estimated OS (95% confidence interval [CI]) rates at 10 and 15 yr were 69% (62-76%) and 53% (45-62%) for RN compared with 80% (73-87%) and 74% (65-83%) following PN (p=0.032). After adjusting for covariates of interest, patients treated with RN were significantly more likely to die from any cause (hazard ratio [HR]: 1.75; 95% CI, 1.08-2.83; p=0.023) or develop stage IV CKD (HR: 4.23; 95% CI, 1.80-9.93; p<0.001) compared with patients who underwent PN. Limitations include the retrospective design, selection bias for surgical approach, and referral bias to a tertiary care facility. CONCLUSIONS: Our data suggest that PN may confer a clinical benefit for improved renal function and better OS compared with RN after excluding the confounding effect of malignancy.

Pathogenesis of bladder calculi in the presence of urinary stasis.

PURPOSE: Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. MATERIALS AND METHODS: Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. RESULTS: Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). CONCLUSIONS: In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis.

Relapses in hepatoblastoma patients: clinical characteristics and outcome--experience of the International Childhood Liver Tumour Strategy Group (SIOPEL).

PURPOSE: To analyse the clinical characteristics and outcome of hepatoblastoma (HB) patients who relapsed after enrolment on SIOPEL studies 1-3. PATIENTS AND METHODS: Analysis of clinical data of all 59 patients (pts) registered in SIOPEL 1-3 studies, who relapsed after achieving complete remission (CR). RESULTS: The median time from the initial diagnosis to relapse was 12 months (4-115 m). The site of relapse was lung N=27, liver N=21, both liver and lung N=5 and other N=5 (missing data-MD: 1 patient). All but 9 pts had an alpha-fetoprotein level >10 ng/mL at the time of relapse. Treatment of the relapse included chemotherapy and surgery N=25, chemotherapy alone N=21, surgery alone N=7 and only palliative treatment N=5 (MD: 1 pt). Overall, 31 pts (52%) achieved a second CR. With a median follow-up of 83 months, 23 pts are alive, (18 in 2nd CR, 5 after a second relapse) and 36 pts have died (35 from disease and 1 from complications). Three-year event-free survival and overall survival are 34% and 43% respectively (95% confidence interval [CI] 0.28-0.69). The main factors associated with a good outcome were PRETEXT group I-III at diagnosis, a high AFP level at relapse and relapse treatment including both chemotherapy and surgery. CONCLUSION: Relapses in HB are rare events occurring in less than 12% of pts after CR. Combined treatment with chemotherapy and surgical removal of the tumour is essential for long-term survival.

Factors influencing urologist treatment preference in surgical management of stone disease.

OBJECTIVE: To assess the surgeon factors influencing the surgical treatment decisions for symptomatic stone disease. The factors influencing the selection of shock wave lithotripsy (SWL), ureteroscopy, or percutaneous nephrolithotomy to treat symptomatic stone disease are not well studied. METHODS: Electronic surveys were sent to urologists with American Medical Association membership. Information on training, practice, and ideal treatment of common stone scenarios was obtained and statistically analyzed. RESULTS: In November 2009, 600 surveys were sent and 180 were completed. High-volume SWL practices (>100 cases annually) were more common in community practice (P < .01), and high-volume ureteroscopy and percutaneous nephrolithotomy practices were more common in academic practice (P = .03). Community practice was associated with SWL selection for proximal urolithiasis and upper pole nephrolithiasis (P < .005). An increasing time since urologic training was associated with SWL selection for proximal urolithiasis and upper pole nephrolithiasis (P < .01). Urologists reporting shock wave lithotriptor ownership were 3-4 times more likely to select SWL for urolithiasis or nephrolithiasis compared with urologists who did not own a lithotripter (P < .01). Routine concern for stent pain and rigid ureteroscope preference (vs flexible) were associated with SWL selection (P < .03). CONCLUSION: Surgeon factors significantly affected urolithiasis treatment selection. SWL was associated with community urology practice, increasing time since training, shock wave lithotriptor ownership, concern for stent pain, and ureteroscope preference.

Metastatic potential of a renal mass according to original tumour size at presentation.

OBJECTIVE: To determine the metastatic potential of renal masses based on original tumour size. MATERIALS AND METHODS: We identified 2651 patients who had undergone surgical resection for a unilateral, sporadic renal tumour between 1990 and 2006. Associations of tumour size with synchronous metastasis at presentation [M1 renal cell carcinoma (RCC)] and development of metastases, death from RCC, and death from any cause after surgery were evaluated using logistic and Cox proportional hazards regression. RESULTS: Of the 2651 patients studied, 182 (6.9%) presented with M1 RCC. Tumour size was significantly greater in patients with M1 RCC than in patients with M0 RCC (a median size of 10 vs 4.5 cm; P < 0.001). Only 1 of the 629 patients (0.2%) with a tumour <3 cm had M1 RCC and that tumour was 2.5 cm. The risk of M1 RCC increased from 1.1% for patients with tumours 3-3.9 cm to 16.5% for patients with tumours ≥7 cm. Of the 2124 patients with M0 RCC, 430 developed distant metastases at a median (range) of 1.4 (0.1-16.2) years after surgery. Only 9 of the 498 patients (1.8%) with a tumour <3 cm developed distant metastases after surgery. Each 1-cm increase in tumour size increased the risk of death from RCC by 20%[hazard ratio (HR) 1.20; 95% confidence interval (CI) 1.18-1.22; P < 0.001] and death from any cause by 10% (HR 1.10; 95% CI 1.09-1.12; P < 0.001). For the 1346 patients who were still alive at last follow-up, the median (range) duration of follow-up was 6.9 (0.1-19.7) years. CONCLUSIONS: Tumour size is significantly associated with metastases in patients with renal masses. Patients with tumours <3 cm have a low risk of synchronous metastatic disease.

Metachronous renal tumours after surgical management of oncocytoma.

OBJECTIVE: • To assess the risk of metachronous renal cell carcinoma (RCC) and benign renal tumours after surgical treatment of primary renal oncocytoma. PATIENTS AND METHODS: • Patients treated for primary renal oncocytoma between 1970 and 2007 were identified. Tumours were reviewed by a urological pathologist and patients were followed for subsequent renal tumours. RESULTS: • Of 424 patients with a median follow up of 7.1 year, 17 (4.0%) patients were diagnosed with a metachronous renal tumour at a median of 3.0 years (range 0.3-16 years). Of the 17 metachronous tumours, eight were oncocytoma, four were RCC and five were not resected or biopsied. • Eleven metachronous tumours occurred after solitary unilateral oncocytoma, five occurred after multifocal unilateral oncocytoma, and one occurred after multifocal bilateral oncocytoma. • Estimated 10-year tumour-free and RCC tumour-free survival was 94.8% and 98.7%, respectively. Patients with primary multifocal oncocytoma were at higher risk of metachronous tumour (hazard ratio 4.0; P = 0.007). Initial oncocytoma size (hazard ratio 1.1; P = 0.11) was not highly associated with risk of tumour recurrence. CONCLUSIONS: • To our knowledge, we report the largest cohort of oncocytoma after surgical management. Metachronous renal neoplasm in a patient with previous oncocytoma is more likely to be benign compared with patients who present with a renal tumour for the first time. Multifocal primary oncocytoma is associated with metachronous renal tumours. • Overall, the risk of metachronous RCC in a patient with an oncocytoma is similar to that of the general population, which does not support the use of routine cross-sectioning imaging surveillance.

Early results of chemotherapy with retroperitoneal lymph node dissection for isolated retroperitoneal recurrence of upper urinary tract urothelial carcinoma after nephroureterectomy.

PURPOSE: Retroperitoneal lymph nodes are a recognized site of relapse in patients undergoing nephroureterectomy (NU) for high grade upper tract urothelial carcinoma (UC). Retrospective studies suggest that retroperitoneal lymph node dissection (RPLND) may be curative at the time of NU for high grade upper tract UC. We hypothesized that chemotherapy followed by RPLND may successfully salvage select patients with isolated retroperitoneal relapse of upper tract UC following prior NU. MATERIALS AND METHODS: We identified four patients with metastatic UC isolated to the subdiaphragmatic retroperitoneal lymph nodes after NU for upper tract UC. These patients had either a stable response or a complete response to chemotherapy and subsequently underwent a complete full bilateral template RPLND. Our primary study endpoints were disease-specific survival and recurrence-free survival. RESULTS: There was no perioperative mortality or long lasting surgery related sequelae in any patient. Two patients had no pathologic evidence of viable cancer at RPLND and are disease-free at 56 and 74 months from surgery. Two patients had evidence of active residual disease and subsequently developed distant disease at 2 months and 32 months after surgery. Both of these patients died of progressive disease at 3 months and 42 months following RPLND. The 5 year DSS and RFS rates were 50% and 50%. CONCLUSIONS: Chemotherapy followed by RPLND for isolated retroperitoneal recurrence after NU for upper tract UC urothelial carcinoma is a feasible and safe treatment that may be potentially therapeutic in select patients.

Percutaneous nephrolithotomy for large or multiple upper tract calculi and autosomal dominant polycystic kidney disease.

PURPOSE: Percutaneous nephrolithotomy is standard therapy for upper tract calculi larger than 2 cm. However, the role of percutaneous nephrolithotomy in patients with autosomal dominant polycystic kidney disease has not been well evaluated. We report our experience with percutaneous nephrolithotomy in patients with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: We retrospectively reviewed the charts of all patients with autosomal dominant polycystic kidney disease and subsequent renal calculi managed by percutaneous nephrolithotomy from October 1981 to the present. RESULTS: We identified 9 patients. Percutaneous nephrolithotomy was performed in 11 kidneys. Flank pain was the presenting symptom in 6 patients. Average stone burden was 2.5 cm (range 1.6 to 3.6). Two access tracts were necessary in 5 kidneys. No intraoperative complications occurred. In 2 kidneys a second stage endoscopic procedure with ultrasonic lithotripsy was required to achieve stone-free status. Nephrostogram 24 hours after the final procedure showed no residual stone fragments in 9 of 11 kidneys (82%). The remaining 2 patients underwent percutaneous basket extraction to render them stone-free. There were no postoperative complications or recurrent stones. No patient required blood transfusion. Mean followup was 2.7 years (range 0.3 to 4). Mean calculated creatinine clearance was stable at 85.6 (range 45.9 to 126.6) and 89.5 mg/dl per minute (range 39.6 to 126.6) preoperatively and at last followup, respectively (p = 0.783). CONCLUSIONS: Autosomal dominant polycystic kidney disease increased operative complexity, the need for multiple percutaneous access tracts and the likelihood of repeat endoscopy. Despite the altered anatomy percutaneous nephrolithotomy was a safe, efficacious approach for autosomal dominant polycystic kidney disease. At last followup there was no stone recurrence and renal function was stable.

Fibroepithelial polyps of the ureter: a single-institutional experience.

OBJECTIVE: Ureteral fibroepithelial polyps (UFP) are rare lesions that may mimic ureteral malignancy, and management is not well defined. We report our experience with the management of UFP. MATERIALS AND METHODS: Between 1945 and 2008, review of our clinical database identified 27 patients who were found to have UFP. Single-pathologist review excluded five patients (three papilloma, one inflammatory pseudopolyp, and one nondiagnostic). Fisher's exact methods were utilized to assess significance of clinical associations. RESULTS: Mean age at diagnosis was 40 years (range 7-73 years) and 68% were male. Mean follow-up was 37 months (range 2-276 months). History of urologic conditions occurred in 13 patients: 7 (32%) urolithiasis, 2 (9%) ureteral stents, 1 (5%) recurrent urinary tract infection, and 3 (14%) ureteropelvic junction obstruction. Mean UFP diameter was 2 cm (range 0.5-4 cm). UFP was more common in the left ureter (68%, 15/22). UFP location within the ureter was proximal in 13 (59%, 15/22), mid in 4 (18%, 4/22), and distal in 4 (18%, 4/22) with multiple UFP along the length of one ureter. Six patients (27%) had multiple UFP. Open surgery, last performed in 1994, was the initial treatment in 10 (45%, 10/22) patients. Endoscopic treatment was performed in 12 (55%, 12/22) patients and was successful in 11. After endoscopic treatment, open surgical treatment was required in 3 patients with ureteral stricture and 1 patient with incomplete polyp resection. UFP reoccurred in 1 patient (1/12) at 26 months and was successfully treated with ureteroscopy. CONCLUSIONS: We conclude that UFP can be successfully managed with endoscopic techniques. Postoperative surveillance is recommended for potential early detection of ureteral stricture or recurrence.

Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras-initiated leukemia.

Gain-of-function NOTCH1 mutations are found in 50%-70% of human T cell acute lymphoblastic leukemia/lymphoma (T-ALL) cases. Gain-of-function NOTCH1 alleles that initiate strong downstream signals induce leukemia in mice, but it is unknown whether the gain-of-function NOTCH1 mutations most commonly found in individuals with T-ALL generate downstream signals of sufficient strength to induce leukemia. We addressed this question by expressing human gain-of-function NOTCH1 alleles of varying strength in mouse hematopoietic precursors. Uncommon gain-of-function NOTCH1 alleles that initiated strong downstream signals drove ectopic T cell development and induced leukemia efficiently. In contrast, although gain-of-function alleles that initiated only weak downstream signals also induced ectopic T cell development, these more common alleles failed to efficiently initiate leukemia development. However, weak gain-of-function NOTCH1 alleles accelerated the onset of leukemia initiated by constitutively active K-ras and gave rise to tumors that were sensitive to Notch signaling pathway inhibition. These data show that induction of leukemia requires doses of Notch1 greater than those needed for T cell development and that most NOTCH1 mutations found in T-ALL cells do not generate signals of sufficient strength to initiate leukemia development. Furthermore, low, nonleukemogenic levels of Notch1 can complement other leukemogenic events, such as activation of K-ras. Even when Notch1 participates secondarily, the resulting tumors show "addiction" to Notch, providing a further rationale for evaluating Notch signaling pathway inhibitors in leukemia.

Robot-assisted laparoscopic transvesical diverticulectomy and simple prostatectomy.

Acquired bladder diverticula are often associated with bladder outlet obstruction (BOO). The increased voiding pressures required to overcome the BOO attenuate the detrusor and promote formation of diverticula. These patients may develop urinary tract infections, bladder stones, and incomplete bladder emptying. Effective treatment must address both the bladder diverticula and BOO. Reports of laparoscopic bladder diverticulectomy with concurrent transurethral resection of the prostate have demonstrated the feasibility of this minimally invasive approach. However, due to longer operative times and technical difficulty of the procedure, the gold-standard treatment remains the open surgical approach of bladder diverticulectomy and transvesical prostatectomy. With the advent of robotic-assisted laparoscopic surgery, application of open surgical principles is increasingly translated to the minimally invasive laparoscopic approach. We report, to our knowledge, the first case of robot-assisted laparoscopic transvesical diverticulectomy and concurrent transvesical simple prostatectomy.

Differential induction of PPAR-gamma by luminal glutamine and iNOS by luminal arginine in the rodent postischemic small bowel.

Using a rodent model of gut ischemia-reperfusion (I/R), we have previously shown that the induction of inducible nitric oxide synthase (iNOS) is harmful, whereas the induction of heme oxygenase 1 (HO-1) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is protective. In the present study, we hypothesized that the luminal nutrients arginine and glutamine differentially modulate these molecular events in the postischemic gut. Jejunal sacs were created in rats at laparotomy, filled with either 60 mM glutamine, arginine, or magnesium sulfate (osmotic control) followed by 60 min of superior mesenteric artery occlusion and 6 h of reperfusion, and compared with shams. The jejunum was harvested for histology or myeloperoxidase (MPO) activity (inflammation). Heat shock proteins and iNOS were quantitated by Western blot analysis and PPAR-gamma by DNA binding activity. In some experiments, rats were pretreated with the PPAR-gamma inhibitor G9662 or with the iNOS inhibitor N-[3(aminomethyl)benzyl]acetamidine (1400W). iNOS was significantly increased by arginine but not by glutamine following gut I/R and was associated with increased MPO activity and mucosal injury. On the other hand, PPAR-gamma was significantly increased by glutamine but decreased by arginine, whereas heat shock proteins were similarly increased in all experimental groups. The PPAR-gamma inhibitor G9662 abrogated the protective effects of glutamine, whereas the iNOS inhibitor 1400W attenuated the injurious effects of arginine. We concluded that luminal arginine and glutamine differentially modulate the molecular events that regulate injurious I/R-mediated gut inflammation and injury. The induction of PPAR-gamma by luminal glutamine is a novel protective mechanism, whereas luminal arginine appears harmful to the postischemic gut due to enhanced expression of iNOS.

Management of French patients with type 2 diabetes mellitus in medical general practice: report of the Mediab observatory.

OBJECTIVES: The Mediab study was conducted to estimate the medical care in French patients with type 2 diabetes mellitus managed by general practitioners on an ambulatory basis, but consIdered as requiring new treatment implementation. METHODS: Five thousand one hundred and fourty eight diabetic patients without any treatment or treated with lifestyle measures either alone or combined with an oral antIdiabetic agent given as monotherapy were included in a cross-sectional study that was conducted on a nationwIde basis by using the ORP (R) methodology. The 4088 patients in whom HbA1c was determined with a reliable method were further classified into 3 categories according to whether HbA1c was<=6.5% (group I, n=525), ranging between 6.6 and 8% (group II, n=1699) or > 8% (group III, n=1864). RESULTS: A large proportion of patients (45.6%) exhibited HbA1c > 8%. Adherence to diet and regular physical activity were progressively decreasing while prevalence of diabetic complications was steadily increasing from group I to III, i.e. when diabetic control was worsening. The complications suffered from severe "underreporting". When complications were reported, the odds-ratio analysis showed that retinopathy is influenced by both the magnitude of glucose excess and the diabetes duration, while renal diseases and macroangiopathy depend mainly on diabetes duration. 38.1% of patients visited a diabetologist, but most of these patients were referred to the speciaList after the inclusion visit. CONCLUSIONS: Despite the development of guIdelines, a large percentage of patients remains poorly-controlled. Future actions should be based on: (i) better collaboration between general practitioners and diabetologists (ii) better detection of complications that suffer from severe "underreporting", (iii) reinforcement of lifestyle recommendations and of pharmacological treatments by shifting from mono- to multi-drug therapy, at earlier stages of the disease.

Risk-adapted treatment for childhood hepatoblastoma. final report of the second study of the International Society of Paediatric Oncology--SIOPEL 2.

SIOPEL 2 was a pilot study designed to test the efficacy and toxicity of two chemotherapy (CT) regimens, one for patients with hepatoblastoma (HB) confined to the liver and involving no more than three hepatic sectors ('standard-risk (SR) HB'), and one for those with HB extending into all four sectors and/or with lung metastases or intra-abdominal extra hepatic spread 'high-risk (HR) HB'. SR-HB patients were treated with four courses of cisplatin (CDDP), at a dose of 80 mg/m(2) every 14 days, delayed surgery, and then two more similar CDDP courses. HR-HB patients were given CDDP alternating every 14 days with carboplatin (CARBO), 500 mg/m(2), and doxorubicin (DOXO), 60 mg/m(2). Two courses of CARBO/DOXO and one of CDDP were given postoperatively. Between October 1995 and May 1998, 77 SR-HB (10 of whom were actually treated with the HR protocol) and 58 HR-HB patients were registered and all 135 could be evaluated. Response rates for the entire SR-HB and HR-HB groups were 90% (95% CI 80-96%) and 78% (95% CI 65-87%), and resection rates were 97% (95% CI 87-99%) and 67% (95% CI 54-79%) including several children undergoing liver transplantation. For SR-HB patients, 3-year overall and progression-free survivals were 91% (+/-7%) and 89% (+/-7%) and for the HR-HB group 53% (+/-13%) and 48% (+/-13%), respectively. The short-term toxicity of these regimens was acceptable, with no toxic deaths. A treatment strategy based on CDDP monotherapy and surgery thus appears effective in SR-HB but, despite CT intensification, only half of the HR-HB patients are long-term survivors. For SR-HB patients, the efficacy of CDDP monotherapy and the CDDP/DOXO ('PLADO') combination are now being compared in a prospective randomised trial (SIOPEL 3).

The Coraliance study: non-compliant behavior. Results after a 6-month follow-up of patients on oral contraceptives.

OBJECTIVES: This follow-up study was planned to establish the frequency with which women miss their contraceptive pill, and to observe their behavior when they forget it. In those women who changed from a continuous cycle to an interrupted type of cycle, or vice versa, the study also aimed to evaluate the impact of this change on the pattern of omission of pills. METHODS: The longitudinal, prospective cohort study included healthy women of child-bearing age for whom a change of pill was being prescribed by their gynecologist. Data were recorded during the 6 months preceding inclusion in the study, and for the 6 months of follow-up; the women were asked to complete a diary in which they recorded the number and exact times of pill omission, and their behavior at each omission. RESULTS: A total of 617 gynecologists included 3316 women into the study; of these, a group of 2418 (73%) revisited the same gynecologist at follow-up. The groups who either visited the same or a different gynecologist were similar with respect to age, oral contraception type, omission type and frequency. A large non-compliance rate and women's difficulties in maintaining safe contraception after missing a pill were observed in the group with follow-up. Women were never risk-free when they missed a pill; they turned to numerous sources for discordant or conflicting information; 15% of 'not-forgetting' women at the pre-inclusion cycle recorded at least one omission at the last cycle of the 6-month follow-up period. Omission fluctuations during the observational period make it difficult to designate 'forgetful' or 'non-forgetful' classes of women. Administration of the pill in a continuous cycle, and probably 'study' and 'auto-questionnaire' effects, contributed to an improvement in compliance. In the group taking the continuous cycle pill, the omission number slightly decreased, particularly on the first day and week of the cycle, irrespective of the initial cycle type. CONCLUSIONS: The importance of the phenomenon of non-compliance rate is confirmed as well as women's difficulties in knowing how to maintain contraceptive safety. The continuous cycle regimen is likely to improve women's compliance during the critical period of the cycle.

Oral contraception: patterns of non-compliance. The Coraliance study.

OBJECTIVES: To determine the number of times women failed to take their oral contraceptive medication and their behavior in response to a missed pill. Another objective was to determine the potential benefit provided by a continuously administered oral contraceptive compared with an oral contraceptive involving a pill-free interval during a 6-month period. METHODS: Healthy women were enrolled in a cohort study; their contraceptive practices were followed by their gynecologists. Data were collected at inclusion using cross-sectional method with retrospective data collection for the previous 6 months and, more specifically, on their previous or their current menstrual cycle. Women on the pill were asked to specify the number of times and precise time at which they missed one or more pills and what they did in response to missing a pill. RESULTS: A total of 617 gynecologists enrolled and followed 3316 patients from six geographic areas throughout France. The mean age of patients was 30 years. Duration of oral contraceptive use was 8 years. During their previous cycle, 23% of women (n = 737) missed a pill at least once. Among women on the pill involving a treatment-free interval, 42% of instances of missing a pill occurred during the first week following the treatment-free interval. In response to missing a pill, patients read the product information leaflet (39%) or asked someone's advice (28%), mainly their gynecologist (63%) or their family physician (18%). Almost one-third of women did not take any specific measures. CONCLUSIONS: Patients on a discontinuous oral contraceptive regimen tended to miss a pill during the first week of treatment. Prescription of a continuous regimen without a treatment-free interval may improve compliance.

Surface morphology of poly(caprolactone)-b-poly(dimethylsiloxane)-b-poly(caprolactone) copolymers: effects on protein adsorption.

Certain triblock copolymer surfaces have beneficial blood contacting properties that remain unexplained from a mechanistic perspective. In this study, poly(caprolactone-block-dimethylsiloxane-block-caprolactone) (PCL-b-PDMS-b-PCL) surfaces are characterized by dynamic contact angle analysis, angle-resolved X-ray photoelectron spectroscopy (XPS), and phase detection imaging atomic force microscopy (AFM). Surface morphology of films cast from 10 wt % MEK solutions are found to be semicrystalline possessing spherulites on the micron scale and alternating semicrystalline PCL-rich and amorphous PDMS-rich lamellae on the nanometer scale. Surface enrichment of the lower surface free energy block, PDMS, is observed using angle-resolved XPS but the surface composition still consists of both copolymer blocks. Films cast from 1 wt % solutions showed similar morphologies but incomplete surface coverage. Different textural features of adsorbed fibrinogen layers on coated and uncoated polypropylene are observed. The hypothesis that patterned block copolymer surfaces can affect protein adsorption and thus influence compatibility is partially supported by the findings of this study.

[Evaluation of continuing medical training in private sector French cardiologists in 1999]. / Evaluation des pratiques de formation médicale continue des cardiologues libéraux francais en 1999.

The authors present the results of a retrospective national enquiry which took place in 1999 and was mailed and faxed to the 3,800 cardiologists practising in the private sector in order to assess the different types of continuous, individual and collective postgraduate training which they had benefited from in the preceding 12 months. The data was analysed by comparison with that obtained from an individualized representative sample in a panel of private sector cardiologists. The results were then compared with the criteria of a yardstick proposed by the National Committee of Continuous Medical Education of 1997, according to the April 25th 1996 decree. The meeting of these criteria would require carrying out 114,000 to 76,000 hour-equivalents of continuous education whereas the present offer is about 100,000 hour-equivalents. The different forms of individual or collective training were compared in the 327 questionnaires which were exploitable following adhesion to the French Society of Cardiology, to the Cardiologists' Union, to local cardiological societies, by age, gender and type of practice. The average number of annual hours of collective education was 52.2 +/- 60.1 hours (25% quartile = 25 hours, 75% = 60 hours). The average value of hours of individual education was 89.7 +/- 89.3 hours (25% quartile = 25 hours; 75% = 120 hours). This evaluation indicates that about 15% of cardiologists practising in the private sector have inadequate continuous medical education and that 68% would satisfy the criteria laid down in 1997. Moreover, the present offer would seem to be adequate providing the criteria of accreditation have been met.