Childhood acute lymphoblastic leukemia (cALL) survivors are at increased risk for bone comorbidities, but accurate screening tools for such comorbidities are limited. Polygenic scores (PGS) could ...stratify cALL survivors for risk of long-term adverse bone outcomes. We evaluated 214 (51% female) cALL survivors from the Prévenir les Effets TArdifs de la LEucémie study (median age 21 yr). Bone mineral density (BMD) measurements were obtained using dual X-ray absorptiometry at the lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and vertebral fractures (VF) were documented using the vertebral deformity criterion. We computed a PGS for adult heel quantitative ultrasound speed of sound (gSOS), known to be associated with the risk of osteoporotic fracture, using imputed genotype data of the participants, and tested it for association with BMD Z-scores and VF risk, adjusting for clinical risk factors, and in sex and prognostic risk-stratified analyses. We found that a gSOS below the mean was associated with lower BMD in all three sites in univariate and multivariate models. In univariate analyses, 1 SD increase in gSOS conferred a 0.16 SD increase in LS-BMD (95% CI 0.005-0.31), whereas a gSOS above the mean was associated with a 0.31 SD higher LS-BMD (95% CI 0.008-0.61), a 0.36 SD higher TB-BMD (95% CI 0.06-0.67), and a 0.43 SD higher FN-BMD (95% CI 0.13-0.72). Models combining gSOS with clinical risk factors explained up to 16% of the variance of BMD phenotypes and obtained an area under the receiver operating characteristic curve for VF of 0.77 in subgroup analyses. Cranial radiation, high cumulative glucocorticoid doses, high risk group, and male sex were significant risk factors for lower BMD Z-scores. In conclusion, a PGS, in combination with clinical risk factors, could be used as a tool to risk stratify cALL survivors for treatment-related bone morbidity.
Abstract Background The relationship between inherited germ-line variations in the 5α-reductase pathways of androgen biosynthesis and the risk of biochemical recurrence (BCR) after radical ...prostatectomy (RP) remains an unexplored area. Objective To determine the link between germ-line variations in the steroid-5α-reductase, α-polypeptide 1 ( SRD5A1 ) and steroid-5α-reductase, α-polypeptide 2 ( SRD5A2 ) genes and BCR. Design, settings, and participants We studied retrospectively two independent cohorts composed of 526 white (25% BCR) and 320 Asian men (36% BCR) with pathologically organ-confined prostate cancer who had a median follow-up of 88.8 and 30.8 mo after surgery, respectively. Measurements Patients were genotyped for 19 haplotype-tagging single nucleotide polymorphisms (htSNPs) in SRD5A1 and SRD5A2 genes, and their prognostic significance on prostate-specific antigen recurrence was assessed using Kaplan-Meier analysis and the Cox regression model. Results and limitations After adjusting for all clinicopathologic risk factors, four SNPs (rs2208532, rs12470143, rs523349, and rs4952197) were associated with BCR in both whites and Asians. The strongest effect was conferred by the SRD5A2 V89L nonsynonymous SNP (rs523349C) with a hazard ratio (HR) of 2.87 (95% confidence interval CI, 2.07–4.00; p = 4 × 10−10 ; 48% BCR). In addition, in whites, the combination of two SNPs, rs518673T in SRD5A1 and rs12470143A in SRD5A2, was associated with a reduced BCR rate for carriers of three or four alleles (HR: 0.37; 95% CI, 0.19–0.71; p = 0.003;16% BCR) compared with noncarriers (38% BCR), whereas the SRD5A2 rs12470143A was significant in Asians (HR: 0.46; 95% CI, 0.28–0.73; p = 0.001). Limitations of our study include few events of androgen-deprivation resistance or cancer-specific death. Conclusions Our study is the first to show positive associations of several SRD5A1 and SRD5A2 variations as independent predictors of BCR after RP.
To evaluate the validity (study 1) and the reproducibility (study 2) of an interviewer-administered food frequency questionnaire (FFQ).
The FFQ was designed at Laval University and contains 91 items ...and 33 subquestions. STUDY 1: The FFQ was compared against a 3-day food record (2 week-days and 1 weekend-day), at week 0, 6 and 12 of a nutritional intervention. STUDY 2: In order to evaluate the reproducibility of the FFQ, 2 registered dietitians administered the FFQ 4-weeks apart among subjects who were not part of the nutritional intervention.
STUDY 1: Mean values for intake of most nutrients assessed by the FFQ and by the 3-day food record were not statistically different. Energy-adjusted correlation coefficients for major macronutrients ranged from 0.36 for proteins to 0.60 for carbohydrates (p < or = 0.01). Agreement analysis revealed that on average, 35% of the subjects were classified in the same quartile when nutrients were assessed by either the 3-day food record or the FFQ. STUDY 2: Significant associations were observed between dietary measurements derived from the two FFQs administered 4 weeks apart. Correlation coefficients for the reproducibility of macronutrients ranged from 0.66 for carbohydrates to 0.83 for lipids after energy adjustment. On average, 46% of the subjects were classified in the same quartile when nutrient intakes were assessed by either FFQ.
These data indicated that the FFQ developed has a good validity and is reproducible.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Antimuscarinics are the pharmacologic mainstay of overactive bladder (OAB) management, but side effects limit their use. Mirabegron, a new molecule with a distinct mechanism of ...action (β3-adrenoreceptor agonist), was recently approved as monotherapy for idiopathic OAB in adults but has not been studied in the pediatric population. Objective To evaluate the efficacy and safety of mirabegron to treat urinary incontinence in children with idiopathic OAB who were refractory to and/or intolerant of antimuscarinics. Design, setting, and participants A prospective off-label study using mirabegron was conducted. Pediatric patients without symptom improvement under behavioral and medical therapies and/or with significant side effects with at least two different antimuscarinic agents were recruited. Outcome measurements and statistical analysis Our primary outcome was better reported efficacy than with the use of prior anticholinergic medication. Secondary end points were tolerability, safety, and satisfaction. Efficacy and tolerability were assessed with voiding diaries, postvoid residuals, urine cultures, electrocardiogram, and vital signs. Families were questioned for continence, side effects, compliance, and Patient Perception of Bladder Condition (PPBC) questionnaire. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis. Results and limitations A total of 58 patients were recruited at a median age of 10.1 yr and were on mirabegron for a median of 11.5 mo. Median bladder capacity improved from 150 ml to 200 ml ( p < 0.001). Continence improved in 52 of 58, with 13 being completely dry. Median PPBC improved from 4.0 to 2.0 ( p < 0.001). Eight patients reported mild or moderate side effects. Absence of a placebo group is a limitation of the study. Conclusions Mirabegron, a novel first-in-class therapy, appeared as a safe and effective alternative for children with idiopathic OAB refractory to antimuscarinics. Patient summary We evaluated the efficacy and safety of mirabegron to treat incontinence in pediatric patients. Continence, median voided volumes, and quality of life were improved after the introduction of mirabegron, and few side effects were reported.
Purpose Mirabegron (β3 adrenoreceptor agonist) is a new molecule with a mechanism of action distinct from antimuscarinics. Combination therapy with solifenacin was recently studied in an adult ...population. We evaluated the efficacy and safety of mirabegron as add-on therapy to treat urinary incontinence in children with idiopathic overactive bladder refractory/intolerant to antimuscarinics. Materials and Methods A prospective off-label study using add-on regimens of mirabegron was conducted in pediatric patients presenting with no symptom improvement while undergoing intensive behavioral and medical therapies and/or significant side effects while undergoing antimuscarinic dose escalation. Our primary outcome was better reported efficacy than with the use of prior antimuscarinic monotherapy. Secondary end points were tolerability, safety and satisfaction. Efficacy and tolerability were assessed based on voiding diaries, post-void residuals, urine cultures, electrocardiograms and vital signs. Families were questioned regarding continence, side effects and compliance. Wilcoxon signed-rank test was used for statistical analysis. Results A total of 35 patients were recruited at a median age of 10.3 years and were administered add-on mirabegron for a median of 16.4 months. Median bladder capacity improved from 50% to 74% expected bladder capacity (p <0.001). Continence improved in all patients, with 12 being completely dry. Post-void residual was increased in 2 patients and 1 urinary tract infection was reported. Seven patients reported mild or moderate side effects, with 2 withdrawals because of side effects (1 patient) and post-void residual (1). Conclusions Add-on mirabegron appears to be a safe alternative for children with refractory overactive bladder. Dual therapy is well tolerated and adjusted dose regimen appears safe in this first pediatric study.
Background
Cohorts of childhood acute lymphoblastic leukemia (cALL) survivors reaching adulthood are increasing. Approximately 30% of survivors meet criteria for low bone mineral density (BMD) ...10 years after diagnosis. We investigated risk factors for low BMD in long‐term cALL survivors.
Methods
We recruited 245 cALL survivors from the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cohort, who were treated with the Dana Farber Cancer Institute protocols, did not experience disease relapse or hematopoietic stem cell transplants, and presented with more than 5 years of event‐free survival. Median time since diagnosis was 15.1 years.
Results
Prevalence of low DXA‐derived BMD (Z‐score ≤−1) ranged between 21.9% and 25.3%, depending on site (lumbar spine (LS‐BMD), femoral neck (FN‐BMD), and total body (TB‐BMD), and between 3.7% and 5.8% for very low BMD (Z‐score ≤−2). Males had a higher prevalence of low BMD than females for all three outcomes (26%–32% vs. 18%–21%), and male sex acted as a significant risk factor for low BMD in all models. Treatment‐related factors such as cumulative glucocorticoid (GC) doses and cranial radiation therapy (CRT) were associated with lower BMDs in the full cohort and in females at the FN‐BMD site.
Conclusion
Low and very low BMD is more prevalent in male cALL survivors. Male sex, high cumulative GC doses, CRT, risk group, and low body mass index (BMI) were identified as risk factors for low BMD. A longer follow‐up of BMD through time in these survivors is needed to establish if low BMD will translate into a higher risk for fragility fractures through adulthood.
Abstract Introduction and Objectives Relevant, meaningful, and achievable data points are critical in objectively assessing quality, utility, and outcomes in female stress urinary incontinence (SUI) ...surgery. A minimum data set female SUI surgery studies was proposed by the first American Urological Association guidelines on the surgical management of female SUI in 1997, but recommendation adherence has been suboptimal. The Female Stress Urinary Incontinence Surgical Publication Working Group (WG) was created from members of several prominent organizations to formulate a recommended standard of study structure, description, and minimum outcome data set to be utilized in designing and publishing future SUI studies. The goal of this WG was to create a body of evidence better able to assess the outcomes of female SUI surgery. Methods The WG reviewed the minimum data set proposed in the 1997 AUA SUI Guideline document, and other relevant literature. The body of literature was examined in the context of the profound changes in the field over the past 25 years. Through a DELPHI process, a standard study structure and minimum data set were generated. Care was taken to balance the value of several meaningful and relevant data points against the burden of creating an excessively difficult or restrictive standard that would disincentivize widespread adoption and negatively impact manuscript production and acceptance. Results The WG outlined standardization in four major areas: (1) study design, (2) pretreatment demographics and characterization of the study population, (3) intraoperative events, and (4) posttreatment evaluation, and complications. Forty‐two items were evaluated and graded as: STANDARD—must be included; ADDITIONAL—may be included for a specific study and is inclusive of the Standard items; OPTIMAL—may be included for a comprehensive study and is inclusive of the Standard and Additional items; UNNECESSARY/LEGACY—not relevant. Conclusions A reasonable, achievable, and clinically meaningful minimum data set has been constructed. A structured framework will allow future surgical interventions for female SUI to be objectively scrutinized and compared in a clinically significant manner. Ultimately, such a data set, if adopted by the academic community, will enhance the quality of the scientific literature, and ultimately improve short and long‐term outcomes for female patients undergoing surgery to correct SUI.
Management of recurrent or persistent stress urinary incontinence (RSI) following primary insertion of a synthetic midurethral sling (MUS) remains a challenge for the urologist since no consensus is ...available to favor one treatment over another. Complete workup should be carried out, including cystoscopy, urodynamics and potentially a pelvic floor ultrasound as a diagnostic adjunct. Various surgical options have been described for RSI, apart from another MUS, including tightening of or shortening a previously placed MUS, a mini-sling, a salvage spiral sling, a colposuspension, the ACT® system, an artificial urinary sphincter or ultimately a urinary diversion. Treatment depends ultimately on the experience and the expertise of the surgeon but it appears most reasonable to offer a repeat MUS (retropubic or transobturator), a pubovaginal sling or bulking agents to women with RSI. Appropriate counseling of patients to set realistic outcomes is key as it may be more practical to aim more for symptomatic improvement than cure.
This study aimed to empirically validate a French version of the Neurogenic Bladder Symptoms Score-Short From (NBSS-SF), a psychometric multidimensional tool to assess lower urinary tract symptoms ...(LUTS) for patients with a neurological condition.
One hundred and five participants with multiple sclerosis or spinal cord injury prospectively completed the questionnaire at baseline and 7-14 days later. The α coefficient of Cronbach (internal consistency) and the intraclass correlation coefficient (ICC) (test-retest reliability) were calculated.
The internal consistency for the overall questionnaire was high (Cronbach's α coefficients from 0.79), while coefficients for each subscale were variable (urinary incontinence 0.91; storage and voiding 0.69; consequences 0.25). For test-retest reliability, 88/105 (84%) patients filled and sent back their questionnaire 10 days (±3.6 days) after baseline version. ICC was 0.90 for the total score and was 0.73 for the urinary incontinence subdomain, 0.79 for storage and voiding, and 0.75 for consequences.
The psychometric qualities of the French version of the NBSS-SF are well-supported, thus providing a valid tool to measure bladder symptoms across three different domains in patients with a neurogenic bladder.
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