Treatment Shaft for Combined Sewer Overflow Detention

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147195/1/wer0434.pd

Failure to recognize Low non-treponemal titer syphilis infections in pregnancy May lead to widespread under-treatment

Objectives: Rates of maternal syphilis have increased five-fold in Brazil in the past decade. While penicillin remains the only appropriate treatment for maternal syphilis, we hypothesized that low non-treponemal titers (<1:16) may lead to reduced penicillin treatment in Brazil. Methods: Using Brazilian Ministry of Health data on women diagnosed with maternal syphilis between January 1, 2010, and December 31, 2018, we conducted a random-effects logistic regression model with a cluster correction at the state level to evaluate predictive factors of penicillin treatment. Results: We observed yearly increases in cases of pregnant women with syphilis from 2010 to 2018. There was significant variation by state: 52,451 cases were reported in São Paulo, followed by 26,838 in Rio de Janeiro. Among 215,937 cases of maternal syphilis, 91·3% received penicillin. In the random-effects model, a non-treponemal titer ≥1:16 was associated with 1·44 higher odds of receiving penicillin (95% confidence interval [CI]: 1·391·48), and prenatal care was associated with a 2·12 increased odds of receiving penicillin (95% CI: 2·022·21). Although there is an association between the absence of prenatal care and inadequate treatment for syphilis, 83·2% of women in this cohort who did not receive penicillin were engaged in prenatal care. Conclusions: Providers may inappropriately exclude low non-treponemal titers and thereby fail to use penicillin treatment in maternal syphilis. While the cause of the maternal syphilis epidemic in Brazil is multifactorial, we believe our findings can be used to develop targeted interventions throughout Brazil as well as shape public health initiatives globally.National Institute of Mental HealthRevisión por pare

Spinopelvic Adaptations in Standing and Sitting Positions in Patients With Adult Spinal Deformity

Purpose To describe spinopelvic adaptations in the standing and sitting positions in patients with adult spinal deformity (ASD). Methods Ninety-five patients with ASD and 32 controls completed health-related quality of life (HRQOL) questionnaires: short form 36 (SF36), Oswestry Disability Index (ODI), and visual analog scale (VAS) for pain. They underwent biplanar radiography in both standing and sitting positions. Patients with ASD were divided into ASD-front (frontal deformity Cobb > 20°, n = 24), ASD-sag (sagittal vertical axis (SVA) > 50 mm, pelvic tilt (PT) > 25°, or pelvic incidence (PI)-lumbar lordosis (LL) > 10°, n = 40), and ASD-hyper thoracic kyphosis (TK >60°, n = 31) groups. Flexibility was defined as the difference (Δ) in radiographic parameters between the standing and sitting positions. The radiographic parameters were compared between the groups. Correlations between HRQOL scores were evaluated. Results All participants increased their SVA from standing to sitting (ΔSVA<0), except for patients with ASD-sag, who tended to decrease their SVA (78-62 mm) and maximize their pelvic retroversion (27-40° vs 10-34° in controls, p<0.001). They also showed reduced thoracic and lumbar flexibility (ΔLL = 3.4 vs 37.1°; ΔTK = −1.7 vs 9.4° in controls, p<0.001). ASD-hyperTK showed a decreased PT while sitting (28.9 vs 34.4° in controls, p<0.001); they tended to decrease their LL and TK but could not reach values for controls (ΔLL = 22.8 vs 37.1° and ΔTK = 5.2 vs 9.4°, p<0.001). The ASD-front had normal standing and sitting postures. ΔSVA and ΔLL were negatively correlated with the physical component scale (PCS of SF36) and ODI (r = −0.39 and r = −0.46, respectively). Conclusion Patients with ASD present with different spinopelvic postures and adaptations from standing to sitting positions, with those having sagittal malalignment most affected. In addition, changes in standing and sitting postures were related to HRQOL outcomes. Therefore, surgeons should consider patient sitting adaptations in surgical planning and spinal fusion. Future studies on ASD should evaluate whether physical therapy or spinal surgery can improve sitting posture and QOL, especially for those with high SVA or PT

Influence of Spino-Pelvic and Postural Alignment Parameters on Gait Kinematics

Introduction: Postural alignment is altered with spine deformities that might occur with age. Alteration of spino-pelvic and postural alignment parameters are known to affect daily life activities such as gait. It is still unknown how spino-pelvic and postural alignment parameters are related to gait kinematics. Research question: To assess the relationships between spino-pelvic/postural alignment parameters and gait kinematics in asymptomatic adults. Methods: 134 asymptomatic subjects (aged 18-59 years) underwent 3D gait analysis, from which kinematics of the pelvis and lower limbs were extracted in the 3 planes. Subjects then underwent full-body biplanar X-rays, from which skeletal 3D reconstructions and spino-pelvic and postural alignment parameters were obtained such as sagittal vertical axis (SVA), center of auditory meatus to hip axis plumbline (CAM-HA), thoracic kyphosis (TK) and radiologic pelvic tilt (rPT). In order to assess the influence of spino-pelvic and postural alignment parameters on gait kinematics a univariate followed by a multivariate analysis were performed. Results: SVA was related to knee flexion during loading response (β = 0.268); CAM-HA to ROM pelvic obliquity (β = -0.19); rPT to mean pelvic tilt (β = -0.185) and ROM pelvic obliquity (β = -0.297); TK to ROM hip flexion/extension in stance (β = -0.17), mean foot progression in stance (β = -0.329), walking speed (β = -0.19), foot off (β = 0.223) and step length (β = -0.181). Significance: This study showed that increasing SVA, CAM-HA, TK and rPT, which is known to occur in adults with spinal deformities, could alter gait kinematics. Increases in these parameters, even in asymptomatic subjects, were related to a retroverted pelvis during gait, a reduced pelvic obliquity and hip flexion/extension mobility, an increased knee flexion during loading response as well as an increase in external foot progression angle. This was associated with a decrease in the walking pace: reduced speed, step length and longer stance phase

Toward understanding the underlying mechanisms of pelvic tilt reserve in adult spinal deformity: the role of the 3D hip orientation

Purpose: To explore 3D hip orientation in standing position in subjects with adult spinal deformity (ASD) presenting with different levels of compensatory mechanisms. Methods: Subjects with ASD (n = 159) and controls (n = 68) underwent full-body biplanar X-rays with the calculation of 3D spinopelvic, postural and hip parameters. ASD subjects were grouped as ASD with knee flexion (ASD-KF) if they compensated by flexing their knees (knee flexion ≥ 5°), and ASD with knee extension (ASD-KE) otherwise (knee flexion < 5°). Spinopelvic, postural and hip parameters were compared between the three groups. Univariate and multivariate analyses were then computed between spinopelvic and hip parameters. Results: ASD-KF had higher SVA (67 ± 66 mm vs. 2 ± 33 mm and 11 ± 21 mm), PT (27 ± 14° vs. 18 ± 9° and 11 ± 7°) and PI-LL mismatch (20 ± 26° vs − 1 ± 18° and − 13 ± 10°) when compared to ASD-KE and controls (all p < 0.05). ASD-KF also had a more tilted (34 ± 11° vs. 28 ± 9° and 26 ± 7°), anteverted (24 ± 6° vs. 20 ± 5° and 18 ± 4°) and abducted (59 ± 6° vs. 57 ± 4° and 56 ± 4°) acetabulum, with a higher posterior coverage (100 ± 6° vs. 97 ± 7° for ASD-KE) when compared to ASD-KE and controls (all p < 0.05). The main determinants of acetabular tilt, acetabular abduction and anterior acetabular coverage were PT, SVA and LL (adjusted R² [0.12; 0.5]). Conclusions: ASD subjects compensating with knee flexion have altered hip orientation, characterized by increased posterior coverage (acetabular anteversion, tilt and posterior coverage) and decreased anterior coverage which can together lead to posterior femoro-acetabular impingement, thus limiting pelvic retroversion. This underlying mechanism could be potentially involved in the hip-spine syndrome

Gait kinematic alterations in subjects with adult spinal deformity and their radiological determinants

Background: Adults with spinal deformity (ASD) are known to have postural malalignment affecting their quality of life. Classical evaluation and follow-up are usually based on full-body static radiographs and health related quality of life questionnaires. Despite being an essential daily life activity, formal gait assessment lacks in clinical practice. Research Question: What are the main alterations in gait kinematics of ASD and their radiological determinants? Methods: 52 ASD and 63 control subjects underwent full-body 3D gait analysis with calculation of joint kinematics and full-body biplanar X-rays with calculation of 3D postural parameters. Kinematics and postural parameters were compared between groups. Determinants of gait alterations among postural radiographic parameters were explored. Results: ASD had increased sagittal vertical axis (SVA:34 ± 59 vs −5 ± 20 mm), pelvic tilt (PT:19 ± 13 vs 11 ± 6°) and frontal Cobb (25 ± 21 vs 4 ± 6°) compared to controls (all p < 0.001). ASD displayed decrease walking speed (0.9 ± 0.3 vs 1.2 ± 0.2 m/s), step length (0.58 ± 0.11 vs 0.64 ± 0.07 m) and increased single support (0.45 ± 0.05 vs 0.42 ± 0.04 s). ASD walked with decreased hip extension in stance (−3 ± 10 vs −7 ± 8°), increased knee flexion at initial contact and in stance (10 ± 11 vs 5 ± 10° and 19 ± 7 vs 16 ± 8° respectively), and decreased knee flexion/extension ROM (55 ± 9 vs 59 ± 7°). ASD had increased trunk flexion (12 ± 12 vs 6 ± 11°) and reduced dynamic lumbar lordosis (−11 ± 12 vs −15 ± 7°, all p < 0.001). Sagittal knee ROM, walking speed and step length were negatively determined by SVA; lack of lumbar lordosis during gait was negatively determined by radiological lumbar lordosis. Significance: Static compensations in ASD persist during gait, where they exhibit a flexed attitude at the trunk, hips and knees, reduced hip and knee mobility and loss of dynamic lordosis. ASD walked at a slower pace with increased single and double support times that might contribute to their gait stability. These dynamic discrepancies were strongly related to static sagittal malalignment

Alterations of gait kinematics depend on the deformity type in the setting of adult spinal deformity

Purpose : To evaluate 3D kinematic alterations during gait in Adult Spinal Deformity (ASD) subjects with different deformity presentations. Methods : One hundred nineteen primary ASD (51 ± 19y, 90F), age and sex-matched to 60 controls, underwent 3D gait analysis with subsequent calculation of 3D lower limb, trunk and segmental spine kinematics as well as the gait deviation index (GDI). ASD were classified into three groups: 51 with sagittal malalignment (ASD-Sag: SVA > 50 mm, PT > 25°, and/or PI-LL > 10°), 28 with only frontal deformity (ASD-Front: Cobb > 20°) and 40 with only hyperkyphosis (ASD-HyperTK: TK > 60°). Kinematics were compared between groups. Results ASD-Sag had a decreased pelvic mobility compared to controls with a decreased ROM of hips (38 vs. 45°) and knees (51 vs. 61°). Furthermore, ASD-Sag exhibited a decreased walking speed (0.8 vs. 1.2 m/s) and GDI (80 vs. 95, all p < 0.05) making them more prone to falls. ASD-HyperTK showed similar patterns but in a less pronounced way. ASD-Front had normal walking patterns. GDI, knee flex/extension and walking speed were significantly associated with SVA and PT (r = 0.30–0.65). Conclusion Sagittal spinal malalignment seems to be the driver of gait alterations in ASD. Patients with higher GT, SVA, PT or PI-LL tended to walk slower, with shorter steps in order to maintain stability with a limited flexibility in the pelvis, hips and knees. These changes were found to a lesser extent in ASD with only hyperkyphosis but not in those with only frontal deformity. 3D gait analysis is an objective tool to evaluate functionality in ASD patients depending on their type of spinal deformity

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial

Background: The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. / Methods: We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7–10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. / Findings: Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60–68). Median follow-up was 4·9 years (IQR 3·0–6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81–1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58–1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3–4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). / Interpretation: These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. / Funding: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs