3D TOF-PET image reconstruction using total variation regularization.

In this paper we introduce a semi-analytic algorithm for 3-dimensional image reconstruction for positron emission tomography (PET). The method consists of the back-projection of the acquired data into the most likely image voxel according to time-of-flight (TOF) information, followed by the filtering step in the image space using an iterative optimization algorithm with a total variation (TV) regularization. TV regularization in image space is more computationally efficient than usual iterative optimization methods for PET reconstruction with full system matrix that use TV regularization. The efficiency comes from the one-time TOF back-projection step that might also be described as a reformatting of the acquired data. An important aspect of our work concerns the evaluation of the filter operator of the linear transform mapping an original radioactive tracer distribution into the TOF back-projected image. We obtain concise, closed-form analytical formula for the filter operator. The proposed method is validated with the Monte Carlo simulations of the NEMA IEC phantom using a one-layer, 50 cm-long cylindrical device called Jagiellonian PET scanner. The results show a better image quality compared with the reference TOF maximum likelihood expectation maximization algorithm.

Performance assessment of the 2 γpositronium imaging with the total-body PET scanners.

PURPOSE: In living organisms, the positron-electron annihilation (occurring during the PET imaging) proceeds in about 30% via creation of a metastable ortho-positronium atom. In the tissue, due to the pick-off and conversion processes, over 98% of ortho-positronia annihilate into two 511 keV photons. In this article, we assess the feasibility for reconstruction of the mean ortho-positronium lifetime image based on annihilations into two photons. The main objectives of this work include the (i) estimation of the sensitivity of the total-body PET scanners for the ortho-positronium mean lifetime imaging using 2γ annihilations and (ii) estimation of the spatial and time resolution of the ortho-positronium image as a function of the coincidence resolving time (CRT) of the scanner. METHODS: Simulations are conducted assuming that radiopharmaceutical is labeled with 44Sc isotope emitting one positron and one prompt gamma. The image is reconstructed on the basis of triple coincidence events. The ortho-positronium lifetime spectrum is determined for each voxel of the image. Calculations were performed for cases of total-body detectors build of (i) LYSO scintillators as used in the EXPLORER PET and (ii) plastic scintillators as anticipated for the cost-effective total-body J-PET scanner. To assess the spatial and time resolution, the four cases were considered assuming that CRT is equal to 500 ps, 140 ps, 50 ps, and 10 ps. RESULTS: The estimated total-body PET sensitivity for the registration and selection of image forming triple coincidences (2γ+γprompt) is larger by a factor of 13.5 (for LYSO PET) and by factor of 5.2 (for plastic PET) with respect to the sensitivity for the standard 2γ imaging by LYSO PET scanners with AFOV = 20 cm. The spatial resolution of the ortho-positronium image is comparable with the resolution achievable when using TOF-FBP algorithms already for CRT = 50 ps. For the 20-min scan, the resolution better than 20 ps is expected for the mean ortho-positronium lifetime image determination. CONCLUSIONS: Ortho-positronium mean lifetime imaging based on the annihilations into two photons and prompt gamma is shown to be feasible with the advent of the high sensitivity total-body PET systems and time resolution of the order of tens of picoseconds.

Estimating relationship between the time over threshold and energy loss by photons in plastic scintillators used in the J-PET scanner.

PURPOSE: The time-over-threshold (TOT) technique is being used widely due to itsimplications in developing the multi-channel readouts, mainly when fast signal processing is required. Using the TOT technique, as a measure of energy loss instead of charge integration methods, significantly reduces the signal readout costs by combining the time and energy information. Therefore, this approach can potentially be utilized in J-PET tomograph which is built from plastic scintillators characterized by fast light signals. The drawback in adopting this technique lies in the non-linear correlation between input energy loss and TOT of the signal. The main motivation behind this work is to develop the relationship between TOT and energy loss and validate it by the J-PET tomograph setup. METHODS: The experiment was performed using a 22Na beta emitter source placed in the center of the J-PET tomograph. This isotope produces photons of two different energies: 511 keV photons from the positron annihilation (direct annihilation or through the formation of a para-positronium atom or pick-off process of ortho-positronium atoms) and a 1275 keV prompt photon. This allows the study of the correlation between TOT values and energy loss for energy ranges up to 1000 keV. Since the photon interacts predominantly via Compton scattering inside the plastic scintillator, there is no direct information of the energy deposition. However, using the J-PET geometry, one can measure the scattering angle of the interacting photon. Since the 22Na source emits photons of two different energies, it is necessary to know unambiguously the energy of incident photons and their corresponding scattering angles in order to estimate energy deposition. In summary, this work presents a dedicated algorithm developed to tag photons of different energies and studying their scattering angles to calculate the energy deposition by the interacting photons. RESULTS: A new method was elaborated to measure the energy loss by photons interacting with plastic scintillators used in the J-PET tomograph. We find the relationship between the energy loss and TOT is non-linear and can be described by the functions TOT = A0 + A1 * ln(E dep + A2) + A3 * (ln(E dep + A2))2 and TOT = A0 - A1 * A2[Formula: see text]. In addition, we also introduced a theoretical model to calculate the TOT as a function of energy loss in plastic scintillators. CONCLUSIONS: A relationship between TOT and energy loss by photons interacting inside the plastic scintillators used in J-PET scanner is established for a deposited energy range of 100-1000 keV.

Evaluation of a surgical training programme for clinical officers in Malawi.

BACKGROUND: Shortages of specialist surgeons in African countries mean that the needs of rural populations go unmet. Task-shifting from surgical specialists to other cadres of clinicians occurs in some countries, but without widespread acceptance. Clinical Officer Surgical Training in Africa (COST-Africa) developed and implemented BSc surgical training for clinical officers in Malawi. METHODS: Trainees participated in the COST-Africa BSc training programme between 2013 and 2016. This prospective study done in 16 hospitals compared crude numbers of selected numbers of major surgical procedures between intervention and control sites before and after the intervention. Volume and outcomes of surgery were compared within intervention hospitals between the COST-Africa trainees and other surgically active cadres. RESULTS: Seventeen trainees participated in the COST-Africa BSc training. The volume of surgical procedures undertaken at intervention hospitals almost doubled between 2013 and 2015 (+74 per cent), and there was a slight reduction in the number of procedures done in the control hospitals (-4 per cent) (P = 0·059). In the intervention hospitals, general surgery procedures were more often undertaken by COST-Africa trainees (61·2 per cent) than other clinical officers (31·3 per cent) and medical doctors (7·4 per cent). There was no significant difference in postoperative wound infection rates for hernia procedures at intervention hospitals between trainees and medical doctors (P = 0·065). CONCLUSION: The COST-Africa study demonstrated that in-service training of practising clinical officers can improve the surgical productivity of district-level hospitals.

'I think we are going to leave these cases'. Obstacles to surgery in rural Malawi: a qualitative study of provider perspectives.

OBJECTIVES: Surgical services at district level in Malawi are poor, yet the majority of the population resides in rural areas. This study aimed to explore the perceived obstacles to surgery from the perspective of the cadre directly responsible for surgical service delivery at district hospitals. METHODS: Qualitative interviews were conducted with 16 clinical officers (COs) receiving surgical training in eight public district hospitals and their 12 trainers. Thematic analysis of data was conducted using a top-down coding method. RESULTS: Despite readiness of the COs to conduct operations, other staff essential for surgery were sometimes unavailable to support them. Respondents attributed this to lack of skills, weak motivation or poor work ethic of their colleagues. Lack of commitment to do surgery, passiveness, lack of initiative in problem-solving and 'laziness' of surgical team members were among the reasons provided by study participants, accounting for unnecessary cancellations of elective surgery and inappropriate referrals of emergency cases. Other factors included infrastructure breakdowns and stock-outs of surgical supplies. There were instances where COs, and their supervisors, showed initiative in finding solutions to problems resulting from poor district hospital management practices. CONCLUSIONS: This study demonstrates how the motivation of surgical team members is a key factor in deciding whether or not to perform operations; and that shortages of supplies or infrastructure need not be an absolute obstacle to service delivery. Scale-up of surgical services at district level requires investments to improve surgical and anaesthetic skills, to strengthen human resources and facility management, and to ensure the availability of reliable infrastructure and essential supplies.

Reticulocyte and erythrocyte hypochromia markers in detection of iron deficiency in adolescent female athletes.

The aim of this study was to analyse the effectiveness of new haematology parameters related to reticulocytes and mature red blood cells to differentiate pre latent and latent iron deficiency. The study included 219 female athletes (aged 15-20 years) representing volleyball, handball, cycling, canoeing, cross-country skiing, swimming and judo. To assess iron status the concentration of ferritin, soluble transferrin receptor (sTfR), iron and total iron binding capacity (TIBC) were determined in serum. In addition to blood morphology, the mean cellular haemoglobin content in erythrocytes (CH) and reticulocytes (CHr), mean cellular haemoglobin concentration in reticulocytes (CHCMr), the percentage of erythrocytes (HYPOm) and reticulocytes (HYPOr) with decreased cellular haemoglobin concentration, the percentage of erythrocytes (LowCHm) and reticulocytes (LowCHr) with decreased cellular haemoglobin content, and percentage of erythrocytes with decreased volume (MICROm) were determined. Subjects with ferritin <30 ng/ml were classified as having stage I (pre-latent) iron deficiency (ID). The second stage (latent ID) was diagnosed when low ferritin was accompanied by elevated sTfR and/or elevated TIBC values. The frequency of ID (without anaemia symptoms) was high, amounting to 60% (stage I in 45%, stage II in 15% of subjects). In subjects with stage I ID significant changes in haematological variables concerned mainly reticulocytes: CHCMr (p<.001), CHr (p<.05), LowCHr (p<.05), HYPOr (p<.001) in comparison to normal iron stores. In athletes with latent ID, there were also significant changes (p<.001) in many indices of mature red blood cells, i.e. haemoglobin concentration (Hb), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), CH, %LowCHm, as well as %MICROm (p<.01) in relation to the group without iron deficiency. The main finding of this study was that the diminished or exhausted iron stores had already caused changes in reticulocytes, and intensified iron deficiency (stage II) increased changes in both reticulocytes' and erythrocytes' hypochromia indices, while microcythaemia symptoms appeared later. This suggests that the markers of hypochromia relating especially to reticulocytes are useful for diagnosis of early ID in athletes with absence of an acute phase reaction.

Determination of some psychotropic drugs in serum and saliva samples by HPLC-DAD and HPLC MS.

A simple, rapid and sensitive HPLC-DAD method has been developed and validated for the simultaneous determination of seven psychotropic drugs (risperidone, citalopram, clozapine,quetiapine, levomepromazine, perazine and aripiprazole) in human serum or saliva samples. The chromatographic analyses were performed on a XSELECT CSH Phenyl-Hexyl column with a mobile phase containing methanol, acetate buffer at pH 3.5 and 0.025mL(-1) diethylamine. The influence of concentration of methanol in injection samples and injection volume on peak symmetry and system efficiency was examined.The full separation of all investigated drugs, good peaks' symmetry and simultaneously high systems efficiency were obtained in applied chromatographic system. The method is suitable for the analysis of investigated drugs in human plasma or saliva for psychiatric patients for control of pharmacotherapy, particularly in combination therapy. HPLC-MS was applied for verification of the presence of drugs and their metabolites in serum and saliva samples from patients.

Chronic GvHD-associated serositis and pericarditis.

Serositis is a rare manifestation of chronic GvHD (cGvHD). No risk factors or laboratory changes associated with this syndrome have been recognized to date, and outcomes have not been described in a large series. We searched our institutional database for patients undergoing allogeneic hematopoietic cell transplant identified as having serositis or pericarditis. Laboratory studies from prior to diagnosis, at diagnosis and post diagnosis of serositis, as well as outcomes from invasive procedures were included. Twenty patients met criteria for cGvHD-associated serositis, and all but three patients had a prior diagnosis of cGvHD. Fifteen were male, and the complication occurred in the setting of immunosuppressant taper in 12 cases. Ten patients required invasive interventions, including pericardial window or stripping. A significant increase in blood monocytes and decrease in serum albumin were identified at diagnosis compared with pre-diagnosis. Out of 20 patients, 17 were treated with steroids, with 12 demonstrating a complete response. These data suggest that cGvHD-associated serositis occurs mainly in the setting of treated as opposed to de novo cGvHD and biomarkers associated with the syndrome include a decrease in albumin and an increase in absolute monocyte count. Outcome data from larger series are required to better understand the optimal management of this rare complication.

The impact of functional training on postural stability and body composition in women over 60.

AIM: The aim of this study was to assess whether functional exercise improved postural stability and body composition in female subjects over 60 years of age. METHODS: Thirty women participated in this study, after being medically qualified for a 3-month functional exercise program. They underwent a series of tests twice, once before starting this functional exercise program, and once again after completing it. These tests consisted of anthropometric examination, stabilometry tests on a Biodex Balance System SD (BBS), and body composition analysis using a Tanita BC420 SMA. RESULTS: The results indicated an improvement in balance parameters among the group of participants between the first test and the second. Statistically significant differences were found in the results of the Postural Stability Test (PST) in static position without visual control protocols and the Fall Risk Test (FRT). In addition, a statistically significant reduction in body weight of 1.16 kg was noted, together with an associated decrease in BMI of 0.35. In terms of body content parameters, the participants' fat content was found to be significantly reduced, by approximately 1.26%. A Wilcoxon test also found a statistically significant (p=0.00002) increase in the content of muscle tissue between the first test and the second. CONCLUSION: The regime of functional training used in this study has a positive impact on the health of elderly females, helping to counteract involutional changes that lead to body imbalance and decreased muscle mass. Further research should seek to further optimize such a regime in this regard.

Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1.

HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor (UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06-1.53; P=0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37-0.80; P=0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.

Changes in physiological tremor resulting from sleep deprivation under conditions of increasing fatigue during prolonged military training.

The aim of the study was to define the changes of the characteristics of physiological postural tremor under conditions of increasing fatigue and lack of sleep during prolonged military training (survival). The subjects of the study were 15 students of the Polish Air Force Academy in Deblin. The average age was 19.9±1.3 years. During the 36-hour-long continuous military training (survival) the subjects were deprived of sleep. Four tremor measurements were carried out for each of the subjects: Day 1 - morning, after rest (measurement 0); Day 2 - morning, after overnight physical exercise (measurement 1); afternoon, after continuous sleep deprivation (measurement 2); Day 3 - morning, after a full night sleep (measurement 3). The accelerometric method using an acceleration measuring kit was applied to analyse tremor. A significant difference between mean values of the index evaluating tremor power in low frequencies L2-4 in measurement 0 and measurement 3 was observed (p<0.01). No significant differences were found in mean values of index L10-20. Mean frequencies F2-4 differed significantly from each other (F2,42=4.53; p<0.01). Their values were 2.94±0.11, 2.99±0.9, 2.93±0.07 and 2.91±0.07 for successive measurements. A gradual, significant decrease of F8-14 was observed (F2,42=5.143; p<0.01). Prolonged sleep deprivation combined with performing tasks demanding constant physical effort causes long-lasting (over 24 hours) changes of the amplitude of low-frequency tremor changes. This phenomenon may significantly influence psychomotor performance, deteriorating the ability to perform tasks requiring movement precision.

The association between ace gene variation and aerobic capacity in winter endurance disciplines.

The aim of the study was to examine the possible relationship between I/D polymorphism of ACE gene and selected indices of aerobic capacity among male and female athletes practising winter endurance sports. Sixty-six well-trained athletes (female n = 26, male n = 40), aged 18.4 ± 2.8 years, representing winter endurance sports (cross-country skiing, n = 48; biathlon, n = 8; Nordic combined, n = 10) participated in the study. Genotyping for ACE I/D polymorphism was performed using polymerase chain reaction. Maximal oxygen consumption (VO2max), maximal running velocity (Vmax) and running velocity at anaerobic threshold (VAT4) were determined in an incremental test to volitional exhaustion on a motorized treadmill. The ACE genotype had no significant effect on absolute VO2max, relative VO2max (divided by body mass or fat free body mass), VAT4 or Vmax. No interaction effect of gender x ACE genotype was found for each of the examined aerobic capacity indices. ACE gene variation was not found to be a determinant of aerobic capacity in either female or male Polish, well-trained endurance athletes participating in winter sports.

Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research.

There are limited data on hematopoietic cell transplantation (HCT) in primary plasma cell leukemia (pPCL), an aggressive plasma cell disorder. We report outcomes of 147 patients with pPCL receiving autologous (n=97) or allogeneic (n=50) HCT within 18 months after diagnosis between 1995 and 2006. Median age was 56 years and 48 years for autologous HCT and allogeneic HCT, respectively. Progression-free survival (PFS) at 3 years was 34% (95% confidence interval (CI), 23-46%) in the autologous group and 20% (95% CI, 10-34%) in the allogeneic group. Cumulative incidence of relapse at 3 years was 61% (95% CI, 48-72%) in the autologous group and 38% (95% CI, 25-53%) in the allogeneic group. Overall survival (OS) at 3 years was 64% (95% CI, 52-75%) in the autologous group and 39% (95% CI, 26-54%) in the allogeneic group. Non-relapse mortality (NRM) at 3 years was 5% (95% CI, 1-11%) in the autologous group and 41% (95% CI, 28-56%) in the allogeneic group. The encouraging OS after autologous HCT, establishes the safety and feasibility of this consolidative treatment option after initial induction therapy for pPCL. Allogeneic HCT, although associated with a significantly lower relapse rate, carries a much higher risk of NRM and no OS benefit.

Tolerability of solifenacin and oxybutynin immediate release in older (> 65 years) and younger (≤ 65 years) patients with overactive bladder: sub-analysis from a Canadian, randomized, double-blind study.

OBJECTIVE: Overactive bladder (OAB) is a common condition whose prevalence increases with age. Antimuscarinic agents are the pharmacologic treatment of choice, but adverse events such as dry mouth may lead to early discontinuation. The purpose of this analysis was to compare the incidence and severity of dry mouth and other adverse events with solifenacin 5 mg/day and oxybutynin immediate release (IR) 15 mg/day in patients ≤ 65 years and >65 years in the Canadian VECTOR study (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients). RESEARCH DESIGN AND METHODS: VECTOR was a randomized, multicentre, prospective, double-blind, double-dummy study in 132 subjects with ≥ 1 urgency episode per 24 h, with or without urgency incontinence, and ≥ 8 micturitions per 24 h for ≥ 3 months. After a 2-week washout, patients received solifenacin 5 mg once daily or oxybutynin IR 5 mg tid for 8 weeks. For the current post-hoc analysis, adverse events were evaluated in subgroups of patients ≤ 65 years and >65 years, using a full logistic regression model, multinomial logit regression model and reduced model. CLINICAL TRIAL REGISTRATION: NCT00431041. RESULTS: The incidence and severity of dry mouth and other adverse events with solifenacin were similar between younger and older patients. In both age subgroups, solifenacin 5 mg/day was associated with fewer episodes and lower severity of dry mouth, and a lower discontinuation rate, compared with oxybutynin IR 15 mg/day. CONCLUSIONS: Solifenacin 5 mg/day was better tolerated than oxybutynin IR 15 mg/day in younger (≤ 65 years) and older (> 65 years) subgroups. Solifenacin was equally well tolerated in both age subgroups. Limitations of the analysis were that the study was not preplanned to perform post-hoc subgroup analysis, patients knew that dry mouth was a primary outcome, and the study used fixed doses of each drug.

Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT.

Haploidentical SCT (HaploSCT) has been most commonly performed using a myeloablative, TBI-based preparative regimen; however, the toxicity with this approach remains very high. We studied the feasibility of a reduced-intensity conditioning regimen in a phase II clinical trial using fludarabine, melphalan and thiotepa and antithymocyte globulin (ATG) for patients with advanced hematological malignancies undergoing T-cell depleted HaploSCT. Twenty-eight patients were entered in the study. Engraftment with donor-derived hematopoiesis was achieved in 78% of patients after a median of 13 days. Six patients experienced primary graft failure, three out of four tested patients had donor-specific anti-HLA antibodies (DSA) (P=0.001). Toxicity included mostly infections. A total of 21 out of 22 patients with AML/myelodysplastic syndrome (MDS) achieved remission after transplant (16 with relapsed/refractory AML). Five out of the 12 patients (42%) with AML/MDS with <15% BM blasts survived long term as compared with none with more advanced disease (P=0.03). HaploSCT with this fludarabine, melphalan and thiotepa and ATG RIC is an effective, well-tolerated conditioning regimen for patients with AML/MDS with low disease burden at the time of transplant and allowed a high rate of engraftment in patients without DSA. Patients with overt relapse fared poorly and require novel treatment strategies.

Allogeneic hematopoietic stem cell transplantation after rituximab-containing myeloablative preparative regimen for acute lymphoblastic leukemia.

We explored the safety and efficacy of rituximab administered in combination with the standard transplant conditioning regimen of cyclophosphamide (Cy) 120 mg/kg and total body irradiation (TBI) 12 Gy for adult patients with acute lymphoblastic leukemia (ALL). Patients were eligible if their disease expressed CD20. Rituximab was administered at 375 mg/m2 weekly for four doses beginning on day -7 of the conditioning regimen. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Thirty-five patients undergoing matched sibling (n = 23) or unrelated donor (n = 12) transplantation were studied, with a median age of 30 years (range 15-55 years). At 2 years, progression-free survival, treatment-related mortality, and overall survival were 30, 24, and 47%, respectively. There was no delay in engraftment or increased incidence of infection. The cumulative incidence of grade II-IV acute GVHD was 17%, and limited and extensive chronic GVHD was 43% at 2 years. The addition of rituximab to the standard Cy/TBI transplant conditioning regimen in ALL was safe and well tolerated, and there was a suggestion of decreased incidence of acute GVHD when compared to historically reported GVHD rates for this group of patients.

High-dose chemotherapy and autologous peripheral blood stem cell transplantation for primary breast cancer refractory to neoadjuvant chemotherapy.

The role of high-dose chemotherapy (HDCT) in patients with refractory breast cancer is not well established. Forty-two female patients (median age of 46 years) with breast cancer refractory to neoadjuvant chemotherapy received HDCT (cyclophosphamide, carmustine and thiotepa) supported by an autologous peripheral blood stem cells transplant. Their disease had been refractory (defined as less than partial response) to one (18 patients) or two (24 patients) regimens of neoadjuvant chemotherapy. Twenty-nine patients had surgery before HDCT. The best response after surgery, HDCT, and radiation therapy was assessed 60 days after transplantation. Thirty patients had complete remission, eight had a PR, one had a minor response, and three had progressive disease. In seven of 13 patients whose disease was inoperable before HDCT, it became operable. After a median follow-up of 42 months, 21 patients were alive, and 15 remained disease free. Five-year overall survival (OS) was 57% (CI, 50-64%), and the estimated 5-year progression-free survival was 40% (CI, 32-48%). Both OS and PFS were better in patients whose disease became operable after chemotherapy than in those whose disease remained inoperable. A randomized study is warranted in this patient population.

Multicenter randomized clinical trial comparing surgery and collagen injections for treatment of female stress urinary incontinence.

OBJECTIVES: To compare, in a multicenter, randomized clinical trial, collagen injections versus surgery with regard to efficacy, quality of life, satisfaction, and complications. METHODS: Of 133 women with stress urinary incontinence, 66 were randomized to collagen injection and 67 to surgery (6 needle bladder neck suspensions, 19 Burch, and 29 slings). After randomization, 15 women refused their allocated treatment. "Intent-to-treat" and "per protocol" analyses were applied. Women assigned to collagen injection could receive up to three injections before it was considered a failure. A "top-up" injection was allowed within 3 months after cure. Success as the primary outcome at 12 months was defined as a dry 24-hour pad test (2.5 g or less of urine) after having received only the allocated intervention. RESULTS: The per protocol analysis showed that the success rate 12 months after collagen injections (53.1%) was much lower than that after surgery (72.2%). The difference was 19.1% (95% confidence interval -36.2% to -2%). The general and disease-specific quality-of-life scores measured by the Rand Medical Outcomes Study 36-item Health Survey and Incontinence Impact Questionnaire were similar in the two groups (P = 0.306). Women treated by surgery were, on average, more satisfied (79.6%) than those treated by collagen injection (67.2%), but the difference was not significant (P = 0.228). Finally, complications were less frequent and severe with collagen injection: 36 events in 23 subjects for collagen injection versus 84 events in 34 subjects for surgery (P = 0.03). CONCLUSIONS: One year after intervention, the success rate of collagen injection as a treatment for stress urinary incontinence was about 19% lower than that after surgery. This has to be tempered by the similar changes in quality of life and satisfaction in both groups and that the number and severity of complications were much greater after surgery than after collagen injection. The results of this study indicate that collagen injections might be a worthwhile alternative to surgery for the treatment of stress urinary incontinence.