Analysis of radioactive waste generated during the cyclotron production of 99mTc.

Past and prospective shortages of medical radioisotopes have driven recent developments in the direct production of 99mTc via the 100Mo(p,2n)99mTc reaction. The cyclotron-based production method has been shown to successfully produce 99mTc, however trace impurities present in the enriched molybdenum target can also lead to the unintended creation of other radioisotopes which constitute waste. The isotopic composition of the waste has to be investigated in order to determine how it can be handled, transported and safely stored. In this article, we report which waste radioisotopes are created alongside 99mTc during target irradiation. Results are based on the gamma spectroscopy of waste produced. Significant complexities in the emission spectra made automated identification of radioisotopes inaccurate; complexities were resolved using a manual radioisotope identification procedure. The impact of target composition, integrated beam current and duration of target irradiation on the waste produced was studied. Results indicate that an average of 0.059 ± 0.003 GBq of waste is generated per 1 GBq of 99mTc produced. Two-thirds of the total waste activity produced was attributed to 99Mo (T 1/2 = 66 h) alone, while a total of fifty radioisotopes were found in the waste. Long-lived isotopes (T 1/2 > 2 months) constituted only 1% of the total waste activity at end of beam (EOB). In conclusion, it was determined that the waste generated during cyclotron-based 99mTc production was acceptably low for routine clinical production.

Community-based provision of direct-acting antiviral therapy for hepatitis C: study protocol and challenges of a randomized controlled trial.

BACKGROUND: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to treatment. Direct-acting antiviral (DAA) treatment can be provided in primary healthcare services (PHCS), improving accessibility, and, potentially, retention in care. Here, we describe our protocol for assessing the effectiveness of providing DAAs in PHCS, and the impact on the HCV care cascade. In addition, we reflect on the challenges of conducting a model of care study during a period of unprecedented change in HCV care and treatment. METHODS: Consenting patients with HCV infection attending 13 PHCS in Australia or New Zealand are randomized to receive DAA treatment at the local tertiary institution (standard care arm), or their PHCS (intervention arm). The primary endpoint is the proportion commenced on DAAs and cured. Treatment providers at the PHCS include: hepatology nurses, primary care practitioners, or, in two sites, a specialist physician. All PHCS offer opioid substitution therapy. DISCUSSION: The Prime Study is the first real-world, randomized, model of care study exploring the impact of community provision of DAA therapy on HCV-treatment uptake and cure. Although the study has faced challenges unique to this period of time characterized by changing treatment and service delivery, the data gained will be of critical importance in shaping health service policy that enables the elimination of HCV. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT02555475 . Registered on 15 September 2015.

Traumatic spinal cord injury in Uganda: a prevention strategy and mechanism to improve home care.

In low- and middle-income countries (LMICs), the burden of traumatic spinal cord injury (TSCI) is largely unknown. The estimated incidence of TSCI in LMICs is 25.5/million/year, and the impact on affected patients and their families is presumed to be immense due to the social structure, limited health system resources and reliance on family to care for those that survive injury to return home. In sub-Saharan Africa, extrapolated regional figures for incidence range from 21 - 29/million/year, and the occurrence of a spinal injury is likely to be fatal within a year.

An integrative review of standardized clinical evaluation tool utilization in anticholinergic drug trials for neurogenic lower urinary tract dysfunction.

STUDY DESIGN: To review prospective and randomized trials studying anticholinergic therapy for neurogenic bladder in SCI to identify whether trials included standardized clinical evaluation tools and reporting measures now recognized to enhance clinical trial data. METHODS: A systematic search via EMBASE, MEDLINE, CENTRAL, CINAHL (Cumulative Index to Nursing and Allied Health Literature), HTA (Health Technology Assessment), CMR (Comprehensive Microbial Resource), HAPI (Health and Psychosocial Instruments) and PsycINFO using the key term spinal cord injury crossed with oxybutynin, tolterodine, darifenacin, solifenacin, fesoterodine, trospium chloride, propiverine, propantheline and anticholinergic(s) for 1946-2015 inclusive. We then collated whether standardized clinical tools, measures and descriptors were used within each study identified: American Spine Injury Association (ASIA) impairment scale; symptom scores validated in SCI; technical methodology for urodynamics/video urodynamics; urinary diaries; and standardized urologic terminology. RESULTS: A total of 1225 entries with 610 unique articles were identified, 14 randomized and 16 prospective studies. In 6/30 the population comprised SCI patients with neurogenic bladder alone; the remainder included mixed neurogenic etiologies. Classification using the ASIA impairment scale was used in <10% of studies; none used symptom scores validated in SCI; <50% reported urodynamic test methodology fully, incorporated urinary diaries or used International Continence Society Standardization Subcommittee urinary tract terminology. CONCLUSION: Integrative review of trials from 1946 to 2015 identified infrequent use of standardized clinical evaluation tools and reporting measures. Data from future trials evaluating therapies for neurogenic bladder would likely be more applicable to specific SCI patients if current standardized classification and descriptors now available were used consistently: for example, the ASIA scale, symptom scores validated in SCI, standardized urodynamic methodology, urinary diaries and urinary tract terminology. Studies recruiting SCI patients exclusively would also provide additional benefit.

A systematic review and comparison of questionnaires in the management of spinal cord injury, multiple sclerosis and the neurogenic bladder.

AIMS: Validated questionnaires are increasingly the preferred method used to obtain historical information. Specialized questionnaires exist validated for patients with neurogenic disease including neurogenic bladder. Those currently available are systematically reviewed and their potential for clinical and research use are described. METHODS: A systematic search via Medline and PubMed using the key terms questionnaire(s) crossed with Multiple Sclerosis (MS) and Spinal Cord Injury (SCI) for the years 1946 to January 22, 2014 inclusive. Additional articles were selected from review of references in the publications identified. Only peer reviewed articles published in English were included. RESULTS: 18 questionnaires exist validated for patients with neurogenic bladder; 14 related to MS, 3 for SCI, and 1 for neurogenic bladder in general; with 4 cross-validated in both MS and SCI. All 18 are validated for both male and female patients; 59% are available only in English. The domains of psychological impact and physical function are represented in 71% and 76% of questionnaires, respectively. None for the female population included elements to measure symptoms of prolapse. CONCLUSION: The last decade has seen an expansion of validated questionnaires to document bladder symptoms in neurogenic disease. Disease specific instruments are available for incorporation into the clinical setting for MS and SCI patients with neurogenic bladder. The availability of caregiver and interview options enhances suitability in clinical practice as they can be adapted to various extents of disability. Future developments should include expanded language validation to the top 10 global languages reported by the World Health Organization.

Cranberry juice for the prevention of pediatric urinary tract infection: a randomized controlled trial.

PURPOSE: Proanthocyanidins found in cranberry have been reported to have in vitro and in vivo antibacterial activity. We determined the effectiveness of cranberry juice for the prevention of urinary tract infections in children. MATERIALS AND METHODS: A total of 40 children were randomized to receive daily cranberry juice with high concentrations of proanthocyanidin vs cranberry juice with no proanthocyanidin for a 1-year period. The study was powered to detect a 30% decrease in the rate of symptomatic urinary tract infection with type I and II errors of 0.05 and 0.2, respectively. Toilet trained children up to age 18 years were eligible if they had at least 2 culture documented nonfebrile urinary tract infections in the calendar year before enrollment. Patients with anatomical abnormalities (except for primary vesicoureteral reflux) were excluded from study. Subjects were followed for 12 months. The participants, clinicians, outcome assessor and statistician were all blinded to treatment allocation. RESULTS: Of the children 39 girls and 1 boy were recruited. Mean and median patient age was 9.5 and 7 years, respectively (range 5 to 18). There were 20 patients with comparable baseline characteristics randomized to each group. After 12 months of followup the average incidence of urinary tract infection in the treatment group was 0.4 per patient per year and 1.15 in the placebo group (p = 0.045), representing a 65% reduction in the risk of urinary tract infection. CONCLUSIONS: Cranberry juice with high concentrations of proanthocyanidin appears to be effective in the prevention of pediatric nonfebrile urinary tract infections. Further studies are required to determine the cost-effectiveness of this approach.

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.

Delayed hypersensitivity and systemic arthralgia following transurethral collagen injection for stress urinary incontinence.

PURPOSE: During a prospective cohort study to determine the effectiveness of and adverse effects associated with transurethral collagen injection for treatment of stress urinary incontinence in women, we observed 3 cases of delayed allergic reaction at the skin test site associated with arthralgia. MATERIALS AND METHODS: A total of 337 women with at least a 1-year history, physical findings and urodynamic abnormalities consistent with stress urinary incontinence, who required pads or protective clothing and who had no or only grade 1 cystocele were enrolled in this prospective cohort study. Adverse effects were documented by a third party at each followup. RESULTS: Delayed reaction at the skin test site occurred in 3 patients (0.9%), and was associated with arthralgias in 2. CONCLUSIONS: The incidence and systemic nature of this type of reaction suggest that gluteraldehyde cross-linked collagen injection is not as innocuous as previously believed. Patients should be counseled regarding the unknown long-term outcome of this complication. Before treatment clinicians should consider double skin testing.

Complications of periurethral collagen injection for stress urinary incontinence.

PURPOSE: Periurethral collagen injection has been advocated as a safe and effective method of treatment for stress urinary incontinence. This study was conducted to determine the complications associated with transurethral collagen injection for treatment of stress urinary incontinence in women. We report the incidence and management of adverse effects. MATERIALS AND METHODS: A total of 337 women with at least a 1-year history, physical findings and urodynamic abnormalities consistent with stress urinary incontinence, who required pads or protective clothing, and who had no or only grade 1 cystocele were enrolled in this prospective cohort study. A third party documented adverse effects at each followup. RESULTS: De novo urinary urgency with incontinence was the most frequent and serious complication, occurring in 12.6% of patients, and in many the symptoms were irreversible. Hematuria (5% of patients) and urinary retention (1.9%) were short-lived and resolved spontaneously. Delayed reaction at the skin test site occurred in 0.9% of the patients (3) and was associated with arthralgias in 2. CONCLUSIONS: Contrary to previous reports that periurethral collagen injection is complication-free, we found an overall incidence of 20% risk of complications in any given individual.

Neoadjuvant androgen withdrawal therapy decreases local recurrence rates following tumor excision in the Shionogi tumor model.

PURPOSE: The role of neoadjuvant androgen withdrawal before radical prostatectomy continues to be defined and remains investigational. It is unknown whether decreases in positive margin rates will translate into lower biochemical and local recurrence rates until long-term followup is available. We determined whether local recurrence rates after tumor excision were less with neoadjuvant compared to adjuvant androgen ablation in the Shionogi tumor model. Androgen withdrawal in this model triggers apoptosis and complete tumor regression but rapidly growing androgen independent tumors inevitably recur after 1 month. Conceptually, the ideal time for excision is after maximal castration induced tumor involution but before outgrowth of androgen resistant clones. MATERIALS AND METHODS: Shionogi tumors were allowed to grow to 1 to 2 gm. before mice were randomly assigned to group 1-tumor excision with wide margins and castration at tumor recurrence and group 2-neoadjuvant castration for 10 days followed by wide excision of the regressed tumor. RESULTS: Tumors recurred locally in 87% of group 1 mice after a median of 17 days (range 6 to 24) and all regressed completely with adjuvant castration. However, androgen independent tumors recurred in 92% of mice after a median of 36 days. In group 2 androgen independent disease recurred in 44% of mice after a median of 40 days. Tumor-free survival was significantly greater in group 2 than in group 1 (56 versus 20%, respectively, p <0.05). Inked surgical resection margins were positive in two-thirds of group 1 and one-third of group 2 mice. CONCLUSIONS: Neoadjuvant androgen withdrawal decreases local recurrence and positive margin rates by 50% after tumor excision in the Shionogi tumor model. Although this model cannot address the issue of effect of neoadjuvant therapy on subclinical metastases, extrapolation of these results to the clinical disease suggests that neoadjuvant therapy may help to decrease not only the positive margin rates but also the subsequent risk of local recurrence following radical prostatectomy.

Neoadjuvant androgen deprivation therapy before radical prostatectomy: who is unlikely to benefit?

OBJECTIVE: To determine which patients undergoing radical prostatectomy for localized cancer are unlikely to benefit from neoadjuvant androgen withdrawal therapy. PATIENTS AND METHODS: Over a 5-year period, 173 patients underwent radical retropubic prostatectomy: 87 patients received no pre-operative androgen withdrawal therapy, for whom the clinical stages were T1b (17 patients), T1c (3), T2a (31) and T2b/c (36). Pre-operative prostate biopsies contained well-differentiated cancer in 43 and moderately differentiated cancer in 44 patients. Serum prostate-specific antigen (PSA) ranged from 0.4 ng/mL to 110.1 ng/mL (median 5.0). The presence of extracapsular disease, positive surgical margins and seminal vesicle involvement were correlated with pre-operative PSA, PSA density (PSAD), the natural logarithm of PSA [In(PSA)], biopsy grade, clinical stage, and sparing of neurovascular bundles. RESULTS: Patients with a PSA < or = 4.0 ng/mL had a rate of extracapsular disease and positive margins of 8.3% and none had seminal vesicle invasion; corresponding rates for patients with a PSA > 4.0 ng/mL were 57%, 51% and 12%, respectively. Multivariate analysis revealed In(PSA) to be the best predictor of extracapsular disease (P < < 0.001), margin positivity (P < < 0.001) and seminal vesicle invasion (P = 0.0019). CONCLUSIONS: These results suggest that in patients who have clinically localized, well or moderately differentiated prostate cancer, a PSA < or = 4.0 ng/mL is predictive for organ-confined disease. This group is unlikely to benefit from neoadjuvant androgen deprivation. Ln(PSA) may be able to improve the accuracy of mathematical multivariate models predicting the presence of extracapsular disease or margin positivity, but this will require verification in larger population-based studies.

Vaginal wall sling for anatomical incontinence and intrinsic sphincter dysfunction: efficacy and outcome analysis.

PURPOSE: A prospective cohort study was done to determine the efficacy and clinical outcome of a new technique for anterior vaginal wall sling construction to treat urinary incontinence due to intrinsic sphincter dysfunction or anatomical incontinence. MATERIALS AND METHODS: Preoperative evaluation included lateral cystography, video urodynamics, cystoscopy and incontinence staging. Postoperative subjective and objective staging outcome measures were prospectively assigned at predetermined regular intervals by a third party. RESULTS: Of the patients 95 had intrinsic sphincter dysfunction and 65 had anatomical incontinence. The repair failed in 7% of the 160 patients who had recurrent incontinence during followup and 9% had de novo urgency incontinence. Time to failure comparing patients with intrinsic sphincter dysfunction and anatomical incontinence was modeled using Kaplan-Meier survival curves, and the log rank test showed no significant difference between the groups (p > 0.05). Logistic regression covariates revealed no significant predictive factors for postoperative failures. Preoperative patient age was the only predictive factor for de novo instability (logistic regression model p < 0.05). CONCLUSIONS: Our initial results indicate that the 2 groups are indistinguishable to date based on current clinical and experimental statistics except for time to full recovery of postoperative voiding and incidence of postoperative instability (regression model p < 0.05).

Lack of correlation between the magnitude of preservation injury and the incidence of acute rejection, need for OKT3, and conversion to FK506 in cyclosporine-treated primary liver allograft recipients.

In order to study further whether a relationship exists between the extent of ischemia-preservation-reperfusion injury (IPRI) and acute rejection (AR) events in liver allografts, we retrospectively reviewed 213 consecutive cyclosporine-treated patients who received their first liver allograft between 1/1/93 and 12/31/93. Of these, 178 fulfilled the study inclusion criteria. The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr posttransplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax < 600 IU/L (n = 43); group 2, ASTmax 600-2000 IU/L (n = 86); and group 3, ASTmax > 2000 IU/L (n = 49). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and UNOS status as covariates. At a median follow-up of 271 days there were no statistically significant differences between groups with respect to the incidence of a first episode of AR (47%, 55%, 51%, respectively, P = NS), the timing of AR (respective medians, 9, 10, and 10 days, P = NS), or the proportion of patients treated with OKT3 (9%, 20%, 12%, respectively, P = NS) or converted to FK506 (16%, 12%, 10%, P = NS). Cox regression confirmed the lack of an independent association between the extent of IPRI and any of these outcomes. We conclude that in UW-preserved, cyclosporine-treated primary liver allografts, no correlation exists between the extent of IPRI and the incidence, timing, severity, or refractoriness of clinically defined AR events.

Vaginal reconstructive surgery for female incontinence and anterior vaginal-wall prolapse.

The surgical procedure of choice to correct stress urinary incontinence using a vaginal approach depends not only on the anatomic origin of the incontinence (hypermobility or intrinsic sphincter dysfunction) but also on the degree of coexistent anterior vaginal wall prolapse. The grade of coexistent cystocele and the finding of a central or lateral defect are important observations that help the surgeon plan the optimum surgical approach. Grade 4 cystocele with central and lateral defects represents the most severe form of anterior vaginal wall prolapse. In this case, the surgical goals are to correct both central and lateral defects, as well as hypermobility related to the mid-urethra and bladder neck.

A prospective trial comparing the efficacy and complications of the modified Dornier HM3 and MFL 5000 lithotriptors for solitary renal calculi.

A prospective randomized study of 198 patients was conducted to compare the efficacy of the modified Dornier HM3 lithotriptor to the MFL 5000 lithotriptor. Entrance criteria included solitary stones at any location within the upper collecting system that had not previously been treated with lithotripsy. Following lithotripsy the patients were evaluated by a blinded radiologist with a plain abdominal film, tomograms and renal ultrasound at 1, 4 and 12 weeks. Patients were classified at 12 weeks after lithotripsy as failing treatment if any stone fragments were imaged. Of the patients 170 were available for complete 3-month followup. No statistical or clinical difference in stone-free rates was apparent for calculi in the ureter or renal pelvis in either group. Of patients with lower caliceal stones 80% had no residual fragments visualized at 12 weeks when treated with the modified HM3 device versus 56% with the MFL 5000 lithotriptor (p = 0.05). Treatment time on the MFL 5000 unit was significantly prolonged compared with the modified HM3 device (0.7 hours versus 0.4 hours, respectively) resulting in fewer patients being treated in a given day (p < 0.001). No statistical difference in complication rates could be found between the 2 machines. Steinstrasse were noted in 10% of the patients treated with the modified HM3 device and 6% of the MFL 5000 group. Subcapsular hematomas were noted in 4% of the MFL 5000 treatment arm compared to 1% in the modified HM3 group. Overall, the MFL 5000 lithotriptor was believed to offer no significant clinical advantage over the modified HM3 device in terms of lithotripsy efficacy, although the multifunctional table did offer more versatility for stone treatment. For a busy lithotripsy center, the modified HM3 lithotriptor is still the most efficacious.

Surgery for female stress urinary incontinence.

With the advent of magnetic resonance imaging, the treatment of female incontinence has undergone a renaissance. This change has primarily been due to superior understanding of anatomy and function of the supports of the urethra, bladder neck and bladder base in the female pelvis.

Transplantation of pediatric cadaver kidneys into adult recipients.

Between July 1987 and July 1993, 762 renal allografts were transplanted into adult recipients at our institution. A total of 83 adults received cadaveric renal transplants from donors aged 5 months to 10 years, while 100 adults who received adult cadaver kidneys during the same period served as a comparison group. Cyclosporine based immunosuppression was used. No difference between the 2 groups was found with respect to recipient age, recipient sex, primary renal disease, HLA matching or the number of recipients with a previous transplant. Actual patient (graft) survivals at 1 and 3 years were 91% (77%) and 86% (68%), respectively, for recipients of pediatric kidneys compared to 99% (92%) and 90% (80%), respectively, for recipients of adult kidneys. Pediatric kidney recipients were more likely to encounter renovascular complications (13% versus 4%, p = 0.023) and more likely to have episodes of acute rejection (p = 0.018). Serum creatinine was equal in the 2 groups at 1 year following transplantation (p = 0.63).