Adverse Events in Placebo Arms of Cancer Trials.

BACKGROUND/AIM: Adverse events (AEs) in cancer trials may be caused by the investigational agents or the underlying disease. Determining the causality is challenging, especially in early cancer drug development when a control arm is lacking. MATERIALS AND METHODS: We carried out a systematic literature review of AE frequencies in placebo arms of randomized trials for malignant solid tumors and hematologic malignancies reported in PubMed from 2016 to January 2022. RESULTS: Among 148 placebo arms, the AEs with the highest reported mean frequencies among all publications were: Fatigue (20.1%), nausea (16.3%), diarrhea (14.3%), abdominal pain (12.4%), and anemia (10.9%); AEs resulting in drug discontinuation were reported in 5.6% of placebo-treated patients and serious AEs in 18.7% of placebo patients. CONCLUSION: The data presented here may be used as a benchmark to help assess drug causality in early development cancer studies without a control arm.

Fatigue in Cancer Treatment Studies: Analysis of Placebo Arms.

BACKGROUND/AIM: Fatigue and asthenia are common in patients with cancer; and identifying the cause as drug toxicity versus cancer progression is difficult, particularly in clinical trials without control arms. MATERIALS AND METHODS: We carried out a systematic literature review of fatigue in placebo arms of randomized cancer trials reported in PubMed from 2000 to 2021. RESULTS: Fatigue/asthenia were reported in 100 out of 134 placebo cohorts, and the average of reported frequencies was 22.8%, with a range of 0-83%. Grade 3 or higher fatigue/asthenia was reported in 2.3% (0-17%). Fatigue/asthenia was positively correlated with nausea (R=0.683) Conclusion: For detection of drug toxicity, observations should be flagged when they are higher than the maximum reported in the placebo arm, and the assessment should be supplemented by comparing observations in early oncology trials to literature placebo arms, including both sample sizes and event numbers.

Preoperative Music Listening in Pelvic Reconstructive Surgery: A Randomized Trial.

OBJECTIVES: We aimed to investigate the effect of music listening on preoperative anxiety compared with usual care in patients undergoing pelvic reconstructive surgery. METHODS: Patients scheduled for pelvic reconstructive surgery were enrolled on the day of surgery. Participants were randomized to either the usual care (control group) or to music listening on headphones (music group) before their surgery. Participants completed the Spielberg State-Trait Anxiety Inventory form Y1 to measure baseline state anxiety levels before surgery and again after 30 minutes of usual care or music listening. The primary outcome was the change in state anxiety score as measured by the State-Trait Anxiety Inventory form Y1. RESULTS: Sixty-nine women completed the study (35 assigned to the control group and 34 assigned to the music group). Analysis of the primary outcome included 66 participants (34 in the control group and 32 in the music group). Improvement in state anxiety was significantly better for patients assigned to music listening (-6.69; SD, 6.98) than for patients assigned to the control group (-1.32; SD, 8.03; P = 0.01). Six weeks postoperatively, patients in the music group (n = 29) reported higher overall satisfaction when compared with those in the control group (n = 31, P = 0.03). CONCLUSION: Patients undergoing pelvic reconstructive surgery present with moderate anxiety on the day of surgery. Allowing patients to listen to their preferred music is a simple intervention that may lower preoperative anxiety and improve satisfaction in this patient population.

Headache Reporting in Oncology Trials Depends on the Demographics of the Study Population.

BACKGROUND/AIM: The frequency of adverse events (AEs) in clinical trials without control arms is difficult to interpret. MATERIALS AND METHODS: This is a systematic literature review of AEs reported from the placebo arms of randomized cancer trials in PubMed between 2008 and 2020. RESULTS: We found 80 placebo patient cohorts in 73 publications, describing 17,968 subjects who received placebo. Headaches were reported in 35 patient cohorts with an average frequency of 12.3% (+/- SD=8.0, range=0.4-34.1), and were more common in cohorts with a median age between 45 and 50 years, with higher performance status, and breast cancer (average 29.8% +/- SD=6.1). AEs leading to discontinuation were reported in 5% of cohorts (+/- SD=5.1, range=0-22.7). CONCLUSION: Considering covariates allows more accurate interpretation of the observed AE frequencies in cancer trials.

Genomic relatedness and clinical significance of Streptococcus mitis strains isolated from the urogenital tract of sexual partners.

Research into the lower urinary tract (LUT) microbiota has primarily focused on its relationship to LUT symptoms (LUTS), taking snapshots of these communities in individuals with and without LUTS. While certain bacterial taxa have been associated with LUTS, or the lack thereof, the temporal dynamics of this community were largely unknown. Recently, we conducted a longitudinal study and found that vaginal intercourse resulted in a shift in species richness and diversity within the LUT microbiota. This is particularly relevant as frequent vaginal intercourse is a major risk factor for urinary tract infection (UTI) in premenopausal women (Aydin et al. Int Urogynecol J 2015;26:795-804). To further investigate the relationship between vaginal intercourse and LUT microbiota, here we present the results of a 3 week study in which daily urogenital specimens were collected from a female participant and her male sexual partner. Consistent with our previous findings, the LUT microbiota changed after vaginal intercourse, most notably a high abundance of Streptococcus mitis was observed post-coitus. We isolated and sequenced S. mitis from both sexual partners finding that: (i) the S. mitis isolates from the female partner's urogenital tract were genomically similar throughout the duration of the study, and (ii) they were related to one isolate from the male partner's oral cavity collected at the end of the study, suggesting transmission between the two individuals. We hypothesize that blooms in S. mitis after vaginal intercourse may play a role in coitus-related UTI. We found that a S. mitis isolate, in contrast to a Lactobacillus jensenii isolate displaced after vaginal intercourse, cannot inhibit the growth of uropathogenic Escherichia coli. Thus, this bloom in S. mitis may provide a window of opportunity for a uropathogen to colonize the LUT.

Urinary retention is rare after colpocleisis and concomitant midurethral sling: a 10-year experience.

OBJECTIVES: The optimal method of managing stress urinary incontinence (SUI) in women undergoing colpocleisis remains unclear, especially in a setting of urinary retention. We aim to compare postoperative retention after colpocleisis with or without concomitant midurethral sling (MUS). METHODS: A retrospective chart review of all women who underwent colpocleisis with or without MUS from October 2007 to October 2017 was performed. Women with preoperative and 2-week postoperative post-void residual volume (PVR) measurements were included. Urinary retention was defined as PVR of ≥100 ml. Analysis included t tests/Wilcoxon rank, Chi-squared/Fisher's exact, and multivariate linear regression models. RESULTS: A total of 231 women with a mean age of 77.7 years (± 6.0 years SD) met the inclusion criteria. One hundred and thirty-eight women underwent colpocleisis alone, whereas 93 women had colpocleisis with MUS. Preoperative retention rates were high (44.9% vs 34.4%, for colpocleisis alone versus with MUS, p = 0.114). Postoperative retention rates were lower and similar between the groups (10.1% vs 11.8%, for colpocleisis alone vs with MUS, p = 0.69). Linear regression models showed the adjusted odds ratio for postoperative urinary retention in patients with concomitant MUS was 1.68 (95% confidence interval: 0.64-4.41) compared with patients with colpocleisis alone and this did not reach statistical significance (p = 0.292). Fortunately, after colpocleisis, women had high rates of resolution of retention, regardless of MUS (80.3% vs 90.6% for colpocleisis alone vs with MUS; p = 0.20). Few women required reoperation for retention (3.1%). CONCLUSIONS: Placement of an MUS at the time of colpocleisis is a safe and effective therapy. This appears to be unaffected by preoperative urinary retention status.

You're How Old? Correlating Perioperative Complication Risk in Octogenarians Undergoing Colpocleisis for Pelvic Organ Prolapse.

OBJECTIVES: Colpocleisis is a surgical treatment of pelvic organ prolapse for elderly women who are no longer sexually active. The risk calculator of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) predicts perioperative complications. We aim to determine if the NSQIP calculated risk correlates with true perioperative complications in women 80 years or older undergoing colpocleisis. METHODS: Octogenarian women who underwent colpocleisis at our institution from 2007 to 2017 were included in this retrospective chart review. Medical comorbidities were entered into ACS NSQIP calculator, and the calculated risk was compared with actual complications. RESULTS: One hundred twenty-six octogenarians were included in the analysis. The true complication rate was higher than predicted by NSQIP (28.6% [36/126] vs 4.3% (SD, ±1.1%), which we attribute to our relatively high detection rate of urinary tract infection (32/36). Four patients (3.2%) had serious complications (pulmonary embolus, deep vein thrombosis, sepsis, and reintubation). In only 57% of cases, NSQIP risk calculation was concordant with true complication, showing significant departure from correct classification (P < 0.0001). The sensitivity and specificity of the NSQIP calculator were 66.7% and 53.3%, respectively. Multivariable analysis showed higher-than-predicted incidence of complications for patients requiring antiplatelet medication (Plavix or aspirin >81 mg vs none; odds ratio, 4.84, 95% confidence interval, 1.72-13.60; P = 0.002) and a diagnosis of hypertension (odds ratio, 4.24; 95% confidence interval, 1.31-13.72; P = 0.016). CONCLUSION: Serious complication rates are low in octogenarians undergoing colpocleisis. The ACS NSQIP risk calculator does not strongly correlate with actual complications. Further refinement and evolvement of the database may improve its predictive value.

Diarrhea in Placebo Arms of Cancer Studies.

Background/Aim: Diarrhea is among the most common adverse events in early oncology clinical trials, and drug causality may be difficult to determine. Materials and Methods: This is a systematic literature review of placebo arms of randomized cancer trials. Results: Anemia was reported in 95 of 127 placebo monotherapy cohorts. Publications involving healthy volunteers and cancer prevention studies reported lower frequencies than those with cancer patients. The average reported frequency of diarrhea grade 1 or higher among studies in cancer patients was 15%. The maximal reported frequencies for grades 1, 2, 3, 4, 5 were 56, 24, 6, 2, and 0%, respectively. Conclusion: When higher diarrhea frequencies than those are observed in treatment arms of clinical trials, then drug causality is likely.

Consideration of pelvic floor myofascial release for overactive bladder.

INTRODUCTION: Physical therapy has been shown to be effective for women with overactive bladder (OAB). We report on our experience with pelvic floor physical therapy (PFPT) with or without myofascial release as treatment for women with symptoms of urinary urgency or urge incontinence. METHODS: We performed a retrospective chart review, of patients who presented to our tertiary care Urogynecology practice. These women were evaluated and treated between August 2016 and December 2016. We abstracted for symptoms as per history of present illness and the pelvic floor muscle examination. PFPT progress notes were reviewed to determine whether patients received myofascial release techniques, or if therapy was limited to behavioral interventions and urge suppression techniques. We recorded the number of PFPT sessions attended, and whether the patient reported improvement. RESULTS: 77 patients with symptoms of OAB met inclusion criteria and initiated PFPT. Myofascial tenderness of the pelvic floor muscles was found in 56.5% of patients. PFPT was limited to behavioral and urge suppression in 18 patients, while 59 patients received myofascial release techniques. Improvement was reported by 71.4% (n = 55/77) of patients. Improvement increased with number of sessions attended: 1-2: 6% (1/17), 3-5: 94% (16/17), 6-8: 91% (29/32), and >8: 80% (9/11) improved, respectively (p < 0.001). Among patients who had myofascial release, 84.7% reported improvement when compared to only 27.8% of patients without myofascial release. CONCLUSIONS: The data support the inclusion of myofascial release during pelvic floor physical therapy for overactive bladder. At least three sessions of PFPT are necessary for patient reported improvement.

Temporal Dynamics of the Adult Female Lower Urinary Tract Microbiota.

Temporal dynamics of certain human microbiotas have been described in longitudinal studies; variability often relates to modifiable factors or behaviors. Early studies of the urinary microbiota preferentially used samples obtained by transurethral catheterization to minimize vulvovaginal microbial contributions. Whereas voided specimens are preferred for longitudinal studies, the few studies that reported longitudinal data were limited to women with lower urinary tract (LUT) symptoms, due to ease of accessing a clinical population for sampling and the impracticality and risk of collecting repeated catheterized urine specimens in a nonclinical population. Here, we studied the microbiota of the LUT of nonsymptomatic, premenopausal women using midstream voided urine (MSU) specimens to investigate relationships between microbial dynamics and personal factors. Using 16S rRNA gene sequencing and a metaculturomics method called expanded quantitative urine culture (EQUC), we characterized the microbiotas of MSU and periurethral swab specimens collected daily for approximately 3 months from a small cohort of adult women. Participants were screened for eligibility, including the ability to self-collect paired urogenital specimens prior to enrollment. In this population, we found that measures of microbial dynamics related to specific participant-reported factors, particularly menstruation and vaginal intercourse. Further investigation of the trends revealed differences in the composition and diversity of LUT microbiotas within and across participants. These data, in combination with previous studies showing relationships between the LUT microbiota and LUT symptoms, suggest that personal factors relating to the genitourinary system may be an important consideration in the etiology, prevention, and/or treatment of LUT disorders.IMPORTANCE Following the discovery of the collective human urinary microbiota, important knowledge gaps remain, including the stability and variability of this microbial niche over time. Initial urinary studies preferentially utilized samples obtained by transurethral catheterization to minimize contributions from vulvovaginal microbes. However, catheterization has the potential to alter the urinary microbiota; therefore, voided specimens are preferred for longitudinal studies. In this report, we describe microbial findings obtained by daily assessment over 3 months in a small cohort of adult women. We found that, similarly to vaginal microbiotas, lower urinary tract (LUT) microbiotas are dynamic, with changes relating to several factors, particularly menstruation and vaginal intercourse. Our study results show that LUT microbiotas are both dynamic and resilient. They also offer novel opportunities to target LUT microbiotas by preventative or therapeutic means, through risk and/or protective factor modification.

Increasing Age Predicts Increasing Residual Urine Volume.

OBJECTIVES: To determine reference values for postvoid residual (PVR) volume for patients referred to a tertiary urogynecology center. METHODS: After Institutional Review Board approval, we performed a retrospective chart review of all new patients presenting to our referral center. We assessed associations between PVR and patient demographics, pelvic floor symptoms, and physical examination by Wilcoxon rank sum or Kruskal-Wallis tests as appropriate. A multivariable logistic regression model was used to calculate odds ratios for patient characteristics associated with PVR in the top age range-specific decile. RESULTS: Three hundred sixty-one patients were included in the analysis. The median PVR was 20 mL (interquartile range, 1st, 3rd quartiles, 10, 50). Older age was associated with higher PVR (P < 0.001). The median PVR in participants younger than 40 years was 10 mL, ages 40 to 49 years was 18 mL, 50 to 69 years was 20 mL, 70 to 79 years was 38 mL and in women older than 79 years was 50 mL. A multivariable analysis showed that prolapse stage (odds ratio [OR], 3.46 with prolapse stage 2-4 vs stage 0-1; P = 0.001), history of stroke (OR, 7.62; [95% CI 2.17-26.77, P = 0.002]), narcotic use (OR, 2.45; [95% CI 1.01-5.92; P = 0.047]), and urinary frequency (OR, 2.61; [95% CI, 1.14-5.98; P = 0.024]) were risk factors for increased PVR (as defined at >90%ile for age), independent of the age-related elevation. CONCLUSIONS: The majority of patients presenting for urogynecologic evaluation had a low PVR with a median of 20 mL. Postvoid residual was higher for older age groups but nearly all volumes were less than 100 mL. The utility of a PVR measurement is highest for patients with pelvic organ prolapse, urinary frequency, narcotic use, or history of stroke.

Oral probiotics and the female urinary microbiome: a double-blinded randomized placebo-controlled trial.

PURPOSE: Probiotics may reduce risk of urinary tract infection by preventing colonization of uropathogens. We aimed to determine the change in the ratio between uropathogens:Lactobacillus (U/L) within the lower urinary tract in response to oral probiotic. METHODS: This was a double-blinded randomized controlled trial of healthy pre-menopausal female volunteers. Participants provided daily voided urine for 3 months including three phases of the trial: 1-baseline, 2-intervention, 3-wash-out. Participants were randomized to an oral probiotic (Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14) versus placebo. The primary outcome was the U/L ratio of daily voided urine, as determined by an enhanced urine culture method. Analysis included t test of the ratios and separate generalized linear mixed effects models (GLMM) for microbiota diversity. RESULTS: 481 samples of seven female participants with mean age 29.1 years (± 5.3 years) were included in the analysis (probiotic n = 4; placebo n = 3). No adverse events were reported. The placebo and probiotic groups had similar mean U/L ratios with no difference between placebo and probiotic groups in Phases 1-3 (p = 0.90, p = 0.58 and p = 0.72, respectively). The probiotic species were never identified in the voided urine. There were no changes between groups in terms of microbiota diversity. CONCLUSION: For young healthy women, the use of oral probiotic did not affect the U/L ratio.

Characterizing anxiety at the first encounter in women presenting to the clinic: the CAFÉ study.

BACKGROUND: Clinically based anxiety questionnaires measure 2 forms of anxiety that are known as state anxiety and trait anxiety. State anxiety is temporary and is sensitive to change; trait anxiety is a generalized propensity to be anxious. OBJECTIVE: Our study aims to characterize the reasons for anxiety among women about the initial consultation for their pelvic floor disorders to measure change in participant state anxiety after the visit and to correlate improvement in anxiety with visit satisfaction. STUDY DESIGN: All new patients at our tertiary urogynecology clinic were invited to participate. After giving consent, participants completed pre- and postvisit questionnaires. Providers were blinded to pre- and postvisit questionnaire responses. The previsit questionnaires included the Pelvic Floor Distress Inventory, the Generalized Anxiety Disorder-7, and the 6-item short form of the Spielberg State Trait Anxiety Inventory. Participants were also asked to list their previsit anxieties. The postvisit questionnaires comprised of the Spielberg State Trait Anxiety Inventory, patient global impression of improvement of participant anxiety, patient satisfaction, and the participant's perception of whether her anxiety was addressed during the visit. The anxieties listed by participants were then reviewed independently and categorized by 2 of the authors. A separate panel arbitrated when there were disagreements among anxiety categories. RESULTS: Fifty primarily white (66%) women with a median age of 53 years (interquartile range, 41-66) completed the study. The visit diagnoses included stress urinary incontinence (54%), urge urinary incontinence (46%), myofascial pain (28%), pelvic organ prolapse (20%), and recurrent urinary tract infection (12%). Less than one-quarter of participants (22%) had a history of anxiety diagnosis. The average previsit Spielberg State Trait Anxiety Inventory score was 42.9 (standard deviation, 11.98) which decreased by an average of 12.60 points in the postvisit (95% confidence interval, -16.56 to -8.64; P<.001). Postvisit decreased anxiety was associated with improvements in the patient global impression of improvement anxiety (P<.001) and participants' perception that their anxiety symptoms had been addressed completely (P=.045). The most reported causes for consultation related anxiety were lack of knowledge of diagnosis and ramifications, personal or social issues, and fear of the physical examination. Participants reported that improvements in anxiety were related to patient education and reassurance, medical staff appreciation, and acceptable treatment plan. Participants who reported complete satisfaction demonstrated a greater decrease in the postvisit Spielberg State Trait Anxiety Inventory scores compared with the participants who did not report complete satisfaction (P=.045). Changes in the Spielberg State Trait Anxiety Inventory score were not associated with the Pelvic Floor Distress Inventory (P=.35) or Generalized Anxiety Disorder-7 scores (P=.78). CONCLUSION: Women with the highest satisfaction after their initial urogynecology visit also demonstrated the largest decreases in anxiety after the visit. Changes in anxiety scores were not correlated with the Pelvic Floor Distress Inventory or with measures of generalized anxiety (Generalized Anxiety Disorder-7). Recognizing and addressing patient anxiety may help physicians better treat their patients and improve overall patient satisfaction.

Pelvic floor myofascial pain in patients with symptoms of urinary tract infection.

OBJECTIVE: To correlate lower urinary tract symptoms typically associated with a urinary tract infection (UTI) with physical examination findings of pelvic floor myofascial pain (PFMP). METHODS: This retrospective review included all new patients presenting to a urogynecology clinic between August 2 and December 19, 2016. Patients completed validated questionnaires, had a catheterized urine specimen, and underwent pelvic examination. Associations between demographics, symptoms, urine culture, and PFMP were analyzed. RESULTS: We included 250 patients with urinary frequency (n=160, 64.0%), urgency (n=155, 62.0%), urgency incontinence (n=140, 56.0%), pelvic pain (n=43, 17.2%), and dysuria (n=25, 10.0%). PFMP was detected in 125 (50.0%) patients and culture-proven UTI in 15 (6.0%) patients. Demographics associated with PFMP were lower prolapse stage (P<0.001), age younger than 50 years (P<0.001), lower parity (P=0.028), and non-white ethnicity (P=0.003). Symptoms associated with PFMP were dysuria (adjusted odds ratio 4.13, 95% confidence interval 1.08-15.78), urgency/frequency (2.72, 1.47-5.04), and patient-reported pelvic pain (2.57, 1.08-6.12). These symptoms were independent predictors in multivariable logistic regression analysis. CONCLUSIONS: Most patients had symptoms associated with UTI; however, culture-confirmed diagnosis was infrequent and PFMT was diagnosed in half of participants. Clinicians treating women with these symptoms are advised to examine the pelvic floor muscles.

Approach to Ureterovaginal Fistula: Examining 13 Years of Experience.

OBJECTIVE: We describe the management and outcomes of ureterovaginal fistulas over a 13-year period and present a treatment algorithm. METHODS: We performed a review of ureterovaginal fistula cases between January 2005 and December 2017 at our tertiary academic center. Demographics, diagnostic approaches, and treatment outcomes were assessed. RESULTS: Nineteen cases of ureterovaginal fistula were identified. Fistulas developed after hysterectomy in 18 cases and cesarean delivery in 1 case. Our primary treatment was conservative management with ureteral stenting in 12 and reimplantation in 6 cases. There was 1 case of spontaneous resolution. Ureteral stenting was successful in 11 (92%) of 12 patients. Stents were left in place for an average of 66 days (27-92 days). Complications of stents included pyelonephritis in 2 cases (18%) and stricture in 1 case (9%). Ultimately, conservative management was successful in treating ureterovaginal fistulas in 10 (83%) of 12 cases. The indications for primary ureteral reimplantation were concurrent vesicovaginal fistula in 3 cases, history of ureteral injury with surgical repair during the index surgery in 2 cases, and a 1-year delay in diagnosis in 1 case. A variety of follow-up surveillance methods were used, including tampon tests, computed tomographic urograms, retrograde pyelograms, and MAG-3 Lasix renal scans. CONCLUSIONS: In carefully selected patients, ureteral stenting results in high cure rates for posthysterectomy ureterovaginal fistulas and should be considered first-line therapy. Complicated ureterovaginal fistulas may be best managed by primary ureteral reimplantation.

Pessary types and discontinuation rates in patients with advanced pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to investigate factors associated with long-term pessary use in patients with advanced pelvic organ prolapse (POP). METHODS: This was a retrospective chart review of patients with POP of stage ≥2 managed with a pessary. Patients were excluded if the date of fitting or follow-up was unavailable. Long-term use was defined as more than 1 year. Patient demographics, pessary fitting, and follow-up visit dates were collected. The primary end point was the duration of use and the prognostic impact of pessary type. Secondary objectives addressed other influencing factors including age, estrogen use, and prolapse stage. The data were analyzed using SPSS version 21. RESULTS: The final analysis included 311 patients. The mean (± standard deviation, SD) duration of pessary use was 7.0 ± 0.72 years (median 5.7 years). Long-term use was found in 76 % (164) of these patients. Factors associated with longer use were age >65 years (p = 0.004) and estrogen use (p = 0.048). The estimated mean (± SD) durations of use of the Gellhorn, open ring, ring with support, cube and donut pessaries were 10.5 ± 0.7 years, 3.4 ± 0.6 years, 1.8 ± 0.2 years, 1.8 ± 0.3 years and 1.7 ± 0.5 years, respectively. The Gellhorn pessary was associated with significantly longer use than other pessary types (10.5 ± 0.7, p < 0.0000001); this finding was independent of age, prolapse stage, hysterectomy, and vaginal estrogen use. CONCLUSIONS: In this retrospective analysis, the duration of use was longest with the Gellhorn pessary. Older age and vaginal estrogen use were associated with longer pessary use.

Conjugated polymer network films of poly(p-phenylene vinylene) with hole-transporting carbazole pendants: dual photoluminescence and electrochromic behavior.

A series of poly(p-phenylene vinylene) (PPV) copolymers functionalized with hole-transport and electrochemically active carbazole units as pendant moieties is reported. These polymers exhibit photoluminescence properties by virtue of the PPV analogous backbone. They were also designed as precursor polymer bearing the electroactive carbazole group to form conjugated polymer network (CPN) films by electrodeposition. The electrochemical polymerization of the pendant units eventually lead to a dual property electro-optically active thin film - photoluminescence (PL) behavior that can be attenuated with CPN formation, and a reversible doping and dedoping processes at controlled potentials that lead to an electrochromic behavior. This reveals the ability to incorporate complementary optical and electro-optical properties within the same film using the CPN approach. It should be possible to design and synthesize other PPV π-conjugated polymers with efficient pendant hole-transport groups exhibiting tunable PL and electrochromism with cross-linking.

Pediatric high grade glioma of the spinal cord: results of the HIT-GBM database.

Little is known about pediatric spinal cord high grade gliomas (SCHGG) beyond their dismal prognosis. Here, we analyzed the HIT-GBM(®) database for the influence of surgical resection on survival. Between 1991 and 2010 the HIT-GBM group collected data from European children diagnosed with high grade glioma. Patients with the following inclusion criteria were analyzed in this study: astrocytic histology, WHO grade III or IV, age at diagnosis <18 years, and tumor localized to the spinal cord. 28 patients (mean age 11.28 years, 14 male) with primary SCHGG were identified. The tumor sizes were measured by the span across adjacent vertebrae and varied greatly (range: 1-20, median: 4). Histology was classified as WHO grade III in 15 and grade IV in 13 tumors. Of note, the four largest tumors identified were WHO grade III. Surgery was classified as complete resection (n = 6), subtotal resection (STR) (n = 7), partial resection (n = 12) or biopsy only (n = 3). 27 patients received chemotherapy, 22 of which also received radiation. With the mean follow-up time of 2.88 (SD ± 2.95) years, 14 patients were still alive resulting in a median overall survival of 2.5 years (SE ± 1.6). The positive prognostic indicators for overall survival were: age younger than 5 years (P = 0.047), WHO grade III (P = 0.046), absence of necrosis (P = 0.025) and gross total resection (GTR) (P = 0.012). The prognosis of SCHGG might not be as miserable as generally assumed. GTR is of benefit. Larger data sets and meta-analysis are necessary to identify patient sub-groups.

Pediatric neuro-oncology in small centers--quality control of network support: the HIT-GBM experience.

BACKGROUND: The quality of care for children with brain tumors might be higher in large medical centers; however, it may be possible to improve the quality of care received in smaller centers if they join an effective network. AIM: This study used the HIT-GBM® database to compare the quality of care provided to pediatric high-grade glioma and diffuse intrinsic pontine glioma patients among various medical centers of differing sizes. PATIENTS AND METHODS: Overall survival was used as a defining parameter. Indirect measures were the time intervals between the first clinical signs of cancer, initial diagnostic imaging, surgery, or chemotherapy and radiation. RESULTS: From 1995 to 2003, 310 children (137 girls and 173 boys, aged 3 to 18 years old) were registered from 72 medical centers in Europe. Center sizes differed from 1 to 17 registered patients. Center size did not affect survival, nor any of the time intervals studied. CONCLUSION: There was no evidence that the quality of care differed between smaller and larger centers.

High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D pilot study.

We conducted a phase II study to test methotrexate (5 g/m(2)), as a single agent prior to radiochemotherapy for pediatric high-grade glioma and diffuse intrinsic pontine glioma. Thirty patients (19 male, median age 10.8) were enrolled. Tumors were located as follows: cortex 10, pons 7, other 13. Tumor resection was classified as gross total in 6, subtotal in 6, partial in 4, biopsy in 11 and not performed in 3. WHO grading of the histology was: IV: 11, III: 12 and II: 3. Patients received methotrexate 5 g/m(2) in 24-hour infusions on days 1 and 15. Subsequently 54 Gy radiation was administered with simultaneous chemotherapy including cisplatin, etoposide, vincristine and ifosfamide as previously described. Eight 6-weeks cycles of maintenance chemotherapy consisted of vincristine 1.5 mg/m(2) on days 1, 8 and 15; lomustine 100 mg/m(2) on day 2 and prednisone 40 mg/kg on days 1-17. Event-free survival rates in the whole group of 30 patients were: 43, 20, and 13% after 1, 2 and 5 years, respectively. The response evaluation after methotrexate was available in 19 of the 24 patients who started treatment with measurable disease: CR: 0, PR: 1, SD 18, PD: 0. After radiochemotherapy the response of 24 patients with measurable disease was CR: 1, PR 10, SD 12, PD 1. Both response and event-free survival were superior to the control group of 330 patients treated in various protocols of the same cooperative group. In subgroup analyses the use of dexamethasone during early treatment was linked to poor event free survival. Giving two cycles of high-dose methotrexate prior to radiochemotherapy was feasible, and the approach was taken forward to a randomized phase III trial.