Improvement of neurogenic urinary dysfunctions in female rats treated with an injection of botulinum toxin A at the epicenter of the spinal cord injured site.

OBJECTIVE: To assess the effect of an injection of botulinum toxin A (BoNT/A) at the epicenter of the spinal cord injury (SCI) site on the recovery of lower urinary tract function in female rats with thoracic SCI. MATERIALS AND METHODS: Twenty-four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham-SS (injected with 5 µL of saline solution), Sham-BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI-SS (injured and injected with saline), SCI-BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind-limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies. RESULTS: A compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS-EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non-voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS-EMG signal and duration of burst electrical activity during effective voiding. CONCLUSION: The severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition.

Assessing bias in GFR estimating equations: improper GFR stratification can yield misleading results.

BACKGROUND: Assessing bias (estimated - measured) is key to evaluating glomerular filtration rate (GFR). Stratification by subgroups can indicate where equations perform differently. However, there is a fallacy in the assessment of two instruments (e.g., eGFR and mGFR) when stratifying on the level of only one of those instruments. Here, we present statistical aspects of the problem and a solution for GFR stratification along with an empirical investigation using data from the CKiD study. METHODS: Compared and contrasted biases (eGFR relative to mGFR) with 95% confidence intervals within strata of mGFR only, eGFR only, and the average of mGFR and eGFR using data from the Chronic Kidney Disease in Children (CKiD) study. RESULTS: A total of 304 participants contributed 843 GFR studies with a mean mGFR of 48.46 (SD = 22.72) and mean eGFR of 48.67 (SD = 22.32) and correlation of 0.904. Despite strong agreement, eGFR significantly overestimated mGFR when mGFR < 30 (+ 6.2%; 95%CI + 2.9%, + 9.7%) and significantly underestimated when mGFR > 90 (-12.2%; 95%CI - 17.3%, - 7.0%). Significant biases in opposite direction were present when stratifying by eGFR only. In contrast, when stratifying by the average of eGFR and mGFR, biases were not significant (+ 1.3% and - 1.0%, respectively) congruent with strong agreement. CONCLUSIONS: Stratifying by either mGFR or eGFR only to assess eGFR biases is ubiquitous but can lead to inappropriate inference due to intrinsic statistical issues that we characterize and empirically illustrate using data from the CKiD study. Using the average of eGFR and mGFR is recommended for valid inferences in evaluations of eGFR biases.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

Estimation of solar resource for vehicle-integrated photovoltaics in urban environments using image-based shade detection.

Vehicle-Integrated Photovoltaics (VIPV) in urban environments face challenges in accurately estimating solar resource due to dynamic shading effects. This research presents a methodology for evaluating VIPV solar resource by analyzing imagery and detecting shade conditions along driving routes. Street image mapping services and obstacle detection algorithms are utilized to determine the shaded or sunny condition of the vehicle at each point. The approach enables the calculation of solar irradiance, considering direct and diffuse components, and identifies energetically optimal driving routes. The methodology provides valuable insights for optimizing MPPT algorithms and assessing VIPV performance in urban settings. It offers a practical tool for sustainable mobility and renewable energy integration.

Trajectories of eGFR after kidney transplantation according to trajectories of eGFR prior to kidney replacement therapies in children with chronic kidney disease.

BACKGROUND: In children with chronic kidney disease (CKD), certain risk factors are associated with faster eGFR decline and earlier kidney failure. Whether these factors have lingering effects on post-transplant eGFR trajectory remains unclear. We characterized pre- and post-transplant eGFR trajectories in pediatric kidney transplant recipients by their pre-kidney replacement therapy (KRT) risk factors. METHODS: We studied eGFR trajectories before KRT initiation and after transplantation among Chronic Kidney Disease in Children (CKiD) Study participants. We used mixed-effects models to compare pre-KRT versus post-transplant eGFR trajectories within individual participants by 7 pre-KRT risk factors: glomerular/non-glomerular etiology, race, preemptive transplant, proteinuria, albuminuria, and systolic/diastolic blood pressure (SBP/DBP). RESULTS: We analyzed 1602 pre-KRT and 592 post-transplant eGFR measurements from 246 transplant recipients. Mean annual eGFR decline was decreased from 18.0% pre-KRT (95%CI, 16.1-19.8) to 5.0% post-transplant (95%CI, 3.3-6.7). All 7 pre-KRT risk factors showed strong associations with faster pre-KRT eGFR decline, but not with post-transplant eGFR decline; only albuminuria, high SBP, and high DBP reached statistical significance with notably attenuated associations. In our multivariable model of the pre-KRT risk factors, post-transplant eGFR decline was more rapid only when albuminuria and high SBP were both present. CONCLUSIONS: eGFR decline substantially slows down after transplant even among children with rapidly progressing forms of CKD. Nonetheless, those who had albuminuria and high SBP before KRT might continue to show faster eGFR decline after transplant, specifically when both risk factors were present. This subgroup might benefit from intensive pre-transplant management for at least one of the two risk factors. A higher resolution version of the Graphical abstract is available as Supplementary information.

Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Children and Adolescents With COVID-19 or Multisystem Inflammatory Syndrome Admitted to U.S. ICUs.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.

Platelet-rich Plasma Promotes Restoration of the Anterior Vaginal Wall for the Treatment of Pelvic Floor Dysfunction in Rats.

STUDY OBJECTIVE: To determine the efficacy of using platelet-rich plasma (PRP) for vaginal wall repair in rats with vaginal wall impairment induced by vaginal distension (VD). DESIGN: A single-blind, randomized study. SETTING: A certified animal research facility. ANIMALS: Twenty-four female Sprague Dawley rats. INTERVENTIONS: Female Sprague Dawley rats were divided into sham (n = 8), VD (n = 8), and VD + PRP (n = 8) groups. Vaginal tissues from the VD group were dissected at 28-day post injury. VD + PRP rats received vaginal PRP injections on the 1st, 7th, 14th, and 21st day after VD and sacrificed on the 28th day. MEASUREMENTS AND MAIN RESULTS: Urodynamic tests were performed in all rats. Immunohistochemistry was used to evaluate matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9). Masson's staining was used to evaluate collagen fibers and calculate collagen volume fraction. Collagen fiber damage was confirmed in the VD group, evidenced by thinner and sparse distribution of collagen fibers, with significantly higher MMP-2 and MMP-9 expression than the sham group (p <.05). The collagen fiber damage in the vaginal wall likely led to pelvic floor dysfunction (PFD), evidenced by significantly decreased bladder leak-point pressure (p <.01) and abdominal leak-point pressure (p <.01) in the VD group compared with the sham group. After completion of the PRP treatment, a significantly higher collagen volume fraction (p <.01) and significantly increased bladder leak-point pressure (p <.05) and abdominal leak-point pressure (p <.01) were achieved in the VD + PRP compared with the VD group, thus indicating repair of the vaginal wall and improvement of PFD. CONCLUSION: PRP injections facilitate the regeneration of vaginal wall tissue, particularly collagen fiber, after VD, leading to functional improvement of PFD. Findings support the feasibility of using PRP as a novel treatment for PFD.

High incidence of stroke and mortality in pediatric critical care patients with COVID-19 in Peru.

INTRODUCTION: Pediatric critical care patients with COVID-19 treated in Peru have higher mortality than those previously reported from other countries. Pediatric providers have reported a high number of patients without comorbidities presenting with hemorrhagic strokes associated with COVID-19. We present a study analyzing the factors associated with mortality in this setting. METHODS: Prospective case-control study that included patients <17 years old admitted to a pediatric critical care unit with a positive test confirming COVID-19. The primary outcome was mortality. Fisher's exact test and the Mann-Whitney U test were used for the analysis. RESULTS: Forty-seven patients were admitted to critical care. The mortality of our study is 21.3%. The mortality of patients with neurological presentation was 45.5%, which was significantly higher than the mortality of acute COVID-19 (26.7%) and MIS-C (4.8%), p 0.18. Other risk factors for mortality in our cohort were strokes and comorbidities. Only one patient presenting with hemorrhagic stroke had an undiagnosed comorbidity. CONCLUSION: Cerebrovascular events associated with COVID-19 in pediatric patients, including infants, must be recognized as one of the more severe presentations of this infection in pediatric patients. IMPACT: Pediatric patients with COVID-19 can present with hemorrhagic and ischemic strokes on presentation. Neurological presentation in pediatric patients with COVID-19 has high mortality. Mortality of pediatric patients with COVID-19 is associated with comorbidities. Pediatric presentation and outcomes of COVID-19 in different regions can be novel to previously described.

Meta-analysis under imbalance in measurement of confounders in cohort studies using only summary-level data.

BACKGROUND: Cohort collaborations often require meta-analysis of exposure-outcome association estimates across cohorts as an alternative to pooling individual-level data that requires a laborious process of data harmonization on individual-level data. However, it is likely that important confounders are not all measured uniformly across the cohorts due to differences in study protocols. This imbalance in measurement of confounders leads to association estimates that are not comparable across cohorts and impedes the meta-analysis of results. METHODS: In this article, we empirically show some asymptotic relations between fully adjusted and unadjusted exposure-outcome effect estimates, and provide theoretical justification for the same. We leverage these results to obtain fully adjusted estimates for the cohorts with no information on confounders by borrowing information from cohorts with complete measurement on confounders. We implement this novel method in CIMBAL (confounder imbalance), which additionally provides a meta-analyzed estimate that appropriately accounts for the dependence between estimates arising due to borrowing of information across cohorts. We perform extensive simulation experiments to study CIMBAL's statistical properties. We illustrate CIMBAL using National Children's Study (NCS) data to estimate association of maternal education and low birth weight in infants, adjusting for maternal age at delivery, race/ethnicity, marital status, and income. RESULTS: Our simulation studies indicate that estimates of exposure-outcome association from CIMBAL are closer to the truth than those from commonly-used approaches for meta-analyzing cohorts with disparate confounder measurements. CIMBAL is not too sensitive to heterogeneity in underlying joint distributions of exposure, outcome and confounders but is very sensitive to heterogeneity of confounding bias across cohorts. Application of CIMBAL to NCS data for a proof-of-concept analysis further illustrates the utility and advantages of CIMBAL. CONCLUSIONS: CIMBAL provides a practical approach for meta-analyzing cohorts with imbalance in measurement of confounders under a weak assumption that the cohorts are independently sampled from populations with the same confounding bias.

Treatment with platelet-rich plasma attenuates proprioceptor abnormalities in a rat model of postpartum stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is the most prevalent form of urinary incontinence, and vaginal delivery is a major risk factor for developing SUI. We evaluated the hypothesis that applying the autologous platelet rich plasma (PRP) to the pelvic floor muscles via injection affects expression of proprioceptors and improves postpartum stress urinary incontinence (PSUI) in rats. METHODS: Virgin female Sprague-Dawley rats were divided into control (n = 10) and experimental group(n = 20). Vaginal dilation was used to establish PSUI, and the rats in the experimental group were further divided into the PSUI group (n = 10) and PSUI+PRP group (n = 10). Pelvic floor muscles from rats in the PSUI+PRP group were positioned under ultrasound guidance for PRP injection. The morphology and number of pelvic floor muscle spindles were assessed using H&E staining, proprioceptors evaluated by gold chloride staining, and changes in the expression of neurotrophin-3 (NT-3) and skeletal myosin MY-32 determined by immunohistochemistry. RESULTS: After 28 days,bladder leak point pressure (BLPP) and abdominal leaking-urine point pressure (ALPP) in rats with PSUI were significantly lower than in control animals (P<0.01). Both BLPP and ALPP increased significantly in the PSUI+PRP group (P<0.01). Compared with the control group, muscle spindle morphology and structure in the PSUI and PSUI+PRP groups had different pathological changes,with higher variations in the PSUI group. The positive signals for NT-3/MY-32 expression in control rats were higher than those from PSUI or PSUI+PRP groups, however, the expression for NT-3/MY-32 in PSUI+PRP animals was higher than that seen in the PSUI group (P < 0.01). CONCLUSIONS: PSUI rats have an abnormal expression of pelvic proprioceptors, which affect proprioceptive function, and further the contractibility of pelvic floor muscles. A PRP injection may restore the sensory function of pelvic proprioceptors, thus improving urine leakage in PSUI rats.

Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort.

OBJECTIVES: To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL). DESIGN: Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL. SETTING: Tertiary children's hospital. PATIENTS: Hospitalized children (0-18 yr) initiated on empiric vancomycin therapy for suspected sepsis. INTERVENTIONS: Retrospective measurement of VTL, eGFR, and clinical variables. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis. CONCLUSIONS: Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.

Perception of a New Prolonged-Release Buprenorphine Formulation in Patients with Opioid Use Disorder: The PREDEPO Study.

AIM: The aim of the study was to assess the acceptance of patients with opioid use disorder (OUD) to switching their opioid dependence treatment (ODT) for a prolonged-release buprenorphine (PRB) injection according to their prior ODT (buprenorphine/naloxone [B/N] or methadone). METHODS: This was an observational, retrospective/cross-sectional, multicentre study of adult patients diagnosed with OUD on ODT. Data collected from diaries were analysed to know their interest and opinion on PRB. Questions with fixed response options were included, and several Likert scales were used. RESULTS: A total of 98 patients were enrolled (B/N: 50.0%, methadone: 50.0%). The mean age was 46.9 ± 8.43 years and 79.6% were males. PRB was similarly perceived by both groups in most variables analysed, receiving a mean score of 7.2/10 (B/N: 7.4, methadone: 7.0; p = 0.520), and approximately 65% of patients said they were willing to switch to PRB (B/N: 63.3%, methadone: 65.3%; p = 0.833). Of these, a higher percentage in the B/N group considered that switching would be easy/very easy (B/N: 90.3%, methadone: 46.9%; p < 0.001) and that they would start PRB when available (B/N: 64.5%, methadone: 34.3%; p = 0.005). More than 90% would prefer the monthly injection (B/N: 93.6%, methadone: 100%; p = 0.514). One-third of patients in both groups were unsure/would not switch their ODT to PRB (B/N: 36.7%, methadone: 34.7%; p = 0.833). The main reason was administration by injection. CONCLUSION: Two-thirds of patients would switch their treatment for PRB, and most patients on B/N considered that switching would be easy. PRB could be a suitable alternative for OUD management.

Evaluation of the hospital care quality perceived by patients with immune-mediated inflammatory diseases from the pharmacy service. SACVINFA study.

WHAT IS KNOWN AND OBJECTIVE: Immune-mediated inflammatory diseases (IMIDs) are a group of chronic and highly disabling diseases. The objective is to evaluate the satisfaction with the health care received by patients with the most prevalent IMIDs in Spain: inflammatory bowel disease (IBD), psoriasis (Ps) psoriatic arthritis (PsA), rheumatoid arthritis (RA) and spondyloarthropathies (SpAs), and to determine the factors that influence patient satisfaction. METHODS: This was an observational, cross-sectional, multicentre study in a real-world evidence context conducted in the Pharmacy Service in four hospital centres of the Community of Madrid that belong to the National Health System. The study included adult patients diagnosed with an IMID who had attended the Pharmacy Service at least three times. The patients were grouped according to the main IMID. Health care satisfaction was evaluated using the chronic patient experience assessment (IEXPAC) questionnaire. The responses to IEXPAC are grouped into three factors: productive interactions, new relational model and patient self-management, with a total score from 0 (worst) to 10 (best experience). Health-related quality of life (HRQoL) was also evaluated using the EQ-5D-5L questionnaire, and pharmacological adherence was evaluated through the Morisky-Green test. RESULTS AND DISCUSSION: A total of 578 patients were analysed (IBD = 25.3%; Ps = 19.7%; SpAs = 18.7%; RA = 18.5%; PsA = 17.8%). The mean age (SD) was 49.8 (12.3) years and 50.7% were male. The average score (SD) for the total IEXPAC sample was 6.6 (1.9). RA was the IMID with the lowest score, at 5.83 (2.0), significantly lower than the scores of Ps (SD) [7.01 (1.7); p = 0.003], IBD [6.83 (1, 9); p = 0.012] and SpAs [6.80 (1.6); p = 0.001]. Productive interactions (SD) [8.5 (1.8)] and patient self-management (SD) [7.3 (2.3)] were the factors with the highest scores, and the new relational model had the lowest score (SD) [3.2 (2.7)]. Male gender, a longer time interval between medication administrations and a higher HRQoL were correlated with better patient satisfaction. Current biological therapy (according to the Anatomical Chemical classification system) also had a significant influence; patients treated with tumour necrosis factor inhibitors and interleukin inhibitors showed greater satisfaction than those treated with selective immunosuppressants. WHAT IS NEW AND CONCLUSION: The IEXPAC results show high general satisfaction with care quality reported by patients with IMIDs treated in the Pharmacy Service. However, there are areas of improvement in care quality specially health professional-patient communication, such as increasing access to information, and promoting and facilitating relationships with patients in similar conditions.

Validation of a Chinese version for the global Pelvic Floor Bother Questionnaire.

PURPOSE: The Pelvic Floor Bother Questionnaire (PFBQ) is a self-administered instrument for determining pelvic floor dysfunction (PFD). The PFBQ was validated in English, but lately in other languages. However, a Chinese version has not been established. Thus, we aimed at validating a Chinese PFBQ version. METHODS: We used a translation-back method to develop a PFBQ Chinese version and validated in 102 women, 51 with at least one PFD symptom participated in the patient group, and 51 without PFD in the control group. Construct validity was assessed by comparing groups and a content validity index (CVI) determined. For test-retest reliability, participants completed the questionnaire twice within 1-week interval and the interclass correlation coefficient (ICC) was determined. Internal consistency was calculated using Cronbach's statistics. RESULTS: Missing information after applying the translated PFBQ did not exceed 4% of any questions. Total scores between control and PFD women were significantly different (2.94 ± 1.84 vs. 10.29 ± 6.64; P < 0.001). The CVI for all items ranged from 0.800 to 1.000, and a good reliability was corroborated (α = 0.677, ICC = 0.938). CONCLUSION: The Chinese PFBQ version is a valid and reliable tool to identify the existence and severity of bothersome symptoms in Chinese women with PFD.

Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease.

Using data (2655 observations from 928 participants) from the Chronic Kidney Disease in Children Study, we developed and internally validated new glomerular filtration rate estimating equations for clinical use in children and young adults: two forms of K × [heigh(ht) / serum creatinine(sCr)] and two forms of K × [1 / cystatin C(cysC)]. For each marker, one equation used a sex-dependent K; in the other, K is sex-and age-dependent. Glomerular filtration rate (GFR) was measured directly by plasma iohexol disappearance. The equations using ht/sCr had sex-specific constants of 41.8 for males and 37.6 for females. In the age- dependent models, K increased monotonically for children 1-18 years old and was constant for young adults 18-25 years. For males, K ranged from 35.7 for one-year-olds to 50.8 for those 18 and older. For females, the values of K ranged from 33.1 to 41.4. Constant K values for cystatin-C equations were 81.9 for males and 74.9 for females. With age-dependency, K varied non-monotonically with the highest values at age 15 for males (K of 87.2) and 12 years for females (K of 79.9). Use of an age-dependent K with ht/sCr models reduced average bias, notably in young children and young adults; age-dependent cystatin-C models produced similar agreement to using a constant K in children under 18 years, but reduced bias in young adults. These age-dependent proposed equations were evaluated alongside estimated GFRs from 11 other published equations for pediatrics and young adults. Only our proposed equations yielded non- significant bias and within 30% accuracy values greater than 85% in both the pediatric and young adult subpopulations.

Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation.

BACKGROUND: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer. METHODS: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial next-generation sequencing panel in liquid biopsy. RESULTS: There were ten males (66.7%), and the median patient's age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR. CONCLUSIONS: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.

Patients'satisfaction and experience in treatment with opioid substitution therapy in Spain. The PREDEPO study. / Satisfacción y experiencia de pacientes en tratamiento con sustitutivos opioides en España. Estudio PREDEPO.

The aim of this study was to compare patients' satisfaction, experience, objectives, and opinion based on their current opioid substitution therapy (OST) (buprenorphine/naloxone (B/N) or methadone). The PREDEPO study is an observational, cross-sectional, multicentric study performed in Spain. Adult patients diagnosed with opioid use disorder (OUD) receiving OST were included. They were asked to fill in a questionnaire regarding their current OST. A total of 98 patients were enrolled (B/N: 50%, methadone: 50%). Mean age was 47 ± 8 years old and 80% were male. Treatment satisfaction was similar between groups. The most frequently reported factor for being "very/quite satisfied" was "being able to distribute the dose at different times throughout the day" (44% B/N vs. 63% methadone; p = .122). A significantly lower proportion of patients in the B/N group versus the methadone group reported that having to collect the medication daily was "very/quite annoying" (19% vs. 52%, p = .032). Treatment objectives reported by the majority of patients were similar between groups ("not feeling in withdrawal anymore", "reduce/definitely stop drug use", "improve my health", and "stop thinking about using daily") except for "not having money problems anymore" (73% B/N vs. 92% methadone; p = .012).  These results suggest there are several unmet expectations regarding current OST. There is a need for new treatments that reduce the burden of OUD, avoid the need for daily dosing, and are less stigmatizing which in turn could improve patient management, adherence and, quality of life.

El objetivo es comparar la satisfacción, experiencia, objetivos y opinión de los pacientes con trastorno por consumo de opioides (TCO) en base a su tratamiento sustitutivo de opioides (TSO) actual (metadona o buprenorfina/naloxona (B/N)). El estudio PREDEPO es un estudio observacional, transversal, multicéntrico desarrollado en España que incluyó pacientes adultos, diagnosticados de TCO y en TSO, quienes contestaron una encuesta sobre su tratamiento actual. Se incluyeron 98 pacientes (B/N:50%, metadona:50%): edad media de 47 ± 8 años y el 80% varones. A nivel de la satisfacción con su tratamiento, los resultados fueron similares entre grupos. El factor "muy/bastante satisfactorio" que se reportó con mayor frecuencia fue "poder repartir las dosis en varios momentos del día" (44% B/N vs. 63% metadona; p = ,122). Se encontraron diferencias significativas en "tener que recoger la medicación diariamente" donde una menor proporción en el grupo B/N contestaron "muy/bastante molesto" versus el grupo metadona (19% vs. 52%, p = ,032). Los objetivos reportados por la mayoría de los pacientes fueron similares entre grupos ("no sentir más síndrome de abstinencia", "disminuir o dejar definitivamente mi consumo de drogas", "mejorar mi estado de salud" y "dejar de pensar en consumir todos los días") excepto en "no tener más problemas de dinero" (72% B/N vs. 92% metadona; p = ,012). Estos resultados evidencian que existen expectativas no cubiertas con los TSO actuales y la necesidad de nuevos tratamientos que disminuyan la carga de la enfermedad, eviten la necesidad de una dosificación diaria y reduzcan el estigma, mejorando así el manejo del paciente, su adherencia y calidad de vida.

Hidden Imputations and the Kaplan-Meier Estimator.

The Kaplan-Meier (KM) estimator of the survival function imputes event times for right-censored and left-truncated observations, but these imputations are hidden and therefore sometimes unrecognized by applied health scientists. Using a simple example data set and the redistribution algorithm, we illustrate how imputations are made by the KM estimator. We also discuss the assumptions necessary for valid analyses of survival data. Illustrating imputations hidden by the KM estimator helps to clarify these assumptions and therefore may reduce inappropriate inferences.

Pelvic floor muscle strength and the incidence of pelvic floor disorders after vaginal and cesarean delivery.

BACKGROUND: Pelvic floor disorders (including urinary and anal incontinence and pelvic organ prolapse) are associated with childbirth. Injury to the pelvic floor muscles during vaginal childbirth, such as avulsion of the levator ani muscle, is associated with weaker pelvic floor muscle strength. As weak pelvic floor muscle strength may be a modifiable risk factor for the later development of pelvic floor disorders, it is important to understand how pelvic floor muscle strength affects the course of pelvic floor disorders over time. OBJECTIVE: To investigate the association between pelvic floor muscle strength and the incidence of pelvic floor disorders, and to identify maternal and obstetrical characteristics that modify the association. MATERIALS AND METHODS: This is a longitudinal study investigating pelvic floor disorders after childbirth. Participants were recruited 5-10 years after their first delivery and were assessed for pelvic floor disorders annually for up to 9 years. Stress incontinence, overactive bladder, and anal incontinence were assessed at each annual visit using the Epidemiology of Prolapse and Incontinence Questionnaire. Pelvic organ prolapse was assessed on physical examination, and was defined as descent of the vaginal walls or cervix beyond the hymen during forceful Valsalva. The primary exposure of interest was pelvic floor muscle strength, defined as the peak pressure during a voluntary pelvic muscle contraction (measured with a perineometer). The relationship between pelvic floor muscle strength and the cumulative incidence (time to event) of each pelvic floor disorder was evaluated using lognormal models, stratified by vaginal vs cesarean delivery. The relative hazard for each pelvic floor disorder (among those women free of the disorder at enrollment and thus more than 5-10 years from first delivery), was estimated using semiparametric proportional hazard models as a function of delivery mode, pelvic floor muscle strength, and other covariates. RESULTS: Of 1143 participants, the median age was 40 (interquartile range, 36.6-43.7) years, and 73% were multiparous. On perineometry, women with at least 1 vaginal delivery were more likely to have a low peak pressure, defined as <20 cm H2O (243 of 588 women with at least 1 vaginal delivery vs 107 of 555 women who delivered all of their children by cesarean delivery, P < .001). Among women who had at least 1 vaginal delivery, a pelvic floor muscle strength of <20 cm H2O was associated with a shorter time to event for stress incontinence (time ratio, 0.67; 95% confidence interval, 0.50-0.90), overactive bladder (time ratio, 0.67; 95% confidence interval, 0.51-0.86), and pelvic organ prolapse (time ratio, 0.76; 95% confidence interval, 0.65-0.88). No such association was found among women who delivered all of their children by cesarean delivery. Among women with at least 1 vaginal delivery and considering only pelvic floor disorders that developed during study observation (5-10 years after the first delivery), and controlling for maternal characteristics (body mass index and genital hiatus), women who had a peak pressure of <20 cm H2O had hazard ratios (relative to ≥20 cm H2O) of 1.16 (95% confidence interval, 0.74-1.81) for stress incontinence, 1.27 (95% confidence interval, 0.78-2.05) for overactive bladder, and 1.43 (95% confidence interval, 0.99-2.07) for pelvic organ prolapse. Among women who delivered all of their children by cesarean delivery, there was no association between muscle strength and relative hazard of pelvic floor disorders when controlling for maternal characteristics. CONCLUSION: After vaginal delivery, but not cesarean delivery, the cumulative incidence of pelvic organ prolapse, stress incontinence, and overactive bladder is associated with pelvic muscle strength, but the associations attenuate when adjusting for genital hiatus and body mass index.

Correction to: Mode of initial renal replacement therapy and transplant outcomes in the chronic kidney disease in children (CKiD) study.

The original version of this article unfortunately contained a mistake.