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PURPOSE: To assess direct costs and risks associated with revision operations for distal junctional kyphosis/failure (DJK) following thoracic posterior spinal instrumented fusions (TPSF) for adolescent idiopathic scoliosis (AIS). METHODS: Children who underwent TPSF for AIS by a single surgeon (2014-2020) were reviewed. Inclusion criteria were minimum follow-up of 2 years, thoracolumbar posterior instrumented fusion with a lower instrumented vertebra (LIV) cranial to L2. Patients who developed DJK requiring revision operations were identified and compared with those who did not develop DJK. RESULTS: Seventy-nine children were included for analysis. Of these, 6.3% developed DJK. Average time to revision was 20.8 ± 16.2 months. Comparing index operations, children who developed DJK had significantly greater BMIs, significantly lower thoracic kyphosis postoperatively, greater post-operative lumbar Cobb angles, and significantly more LIVs cranial to the sagittal stable vertebrae (SSV), despite having statistically similar pre-operative coronal and sagittal alignment parameters and operative details compared with non-DJK patients. Revision operations for DJK, when compared with index operations, involved significantly fewer levels, longer operative times, greater blood loss, and longer hospital lengths of stay. These factors resulted in significantly greater direct costs for revision operations for DJK ($76,883 v. $46,595; p < 0.01). CONCLUSIONS: In this single-center experience, risk factors for development of DJK were greater BMI, lower post-operative thoracic kyphosis, and LIV cranial to SSV. As revision operations for DJK were significantly more costly than index operations, all efforts should be aimed at strategies to prevent DJK in the AIS population.
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Cifose , Reoperação , Escoliose , Fusão Vertebral , Vértebras Torácicas , Humanos , Escoliose/cirurgia , Fusão Vertebral/economia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Cifose/cirurgia , Adolescente , Feminino , Reoperação/economia , Reoperação/estatística & dados numéricos , Masculino , Vértebras Torácicas/cirurgia , Criança , Estudos Retrospectivos , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Bromodomain and extra-terminal domain proteins (BET proteins) are epigenetic reader proteins that have been implicated in regulating gene expression through binding to chromatin and interaction with transcription factors. These proteins are located in the nucleus and are responsible for recognizing acetylated lysine residues on histones, reading epigenetic messages, recruiting key transcription factors, and thereby regulating gene expression. BET proteins control the transcription of genes responsible for maladaptive effects in inflammation, cancer, and renal and cardiovascular diseases. Given the multifaceted role of BET proteins in the pathogenesis of various diseases, several small molecule inhibitors of BET proteins have been developed as potential therapeutic targets for treating different diseases in recent years. However, while many nonselective BET inhibitors are indicated for the treatment of cancer, a selective BET inhibitor, apabetalone, is the only oral BET inhibitor in phase III clinical trials for the treatment of cardiovascular diseases and others. Thus, this review aims to present and discuss the preclinical and clinical evidence for the beneficial effects and mechanism of action of apabetalone for treating various diseases.
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Purpose: To analyze the annual use of hip arthroscopy (HA) and Bernese periacetabular osteotomy (PAO) for the treatment of hip dysplasia (HD), as well as postoperative outcomes, including ipsilateral reoperations. Methods: International Classification of Diseases, Ninth and Tenth Revision, codes were used to query the PearlDiver Mariner database from January 2010 through January 2022 to identify patients aged 10 to 59 years who had a presenting diagnosis of HD and subsequently underwent (1) HA; (2) PAO; or (3) combined HA and PAO (HA-PAO, defined as PAO on the same day or within 28 days after HA). We analyzed annual rates for each treatment, as well as rates of postoperative emergency visits, readmissions, and 5-year ipsilateral secondary operations (determined via Kaplan-Meier analysis). Results: There were 32,068 patients who underwent surgical treatment of HD. For HA, PAO, and HA-PAO, there were 29,700, 2,083, and 285 patients, respectively. All operations had the greatest percent-increase from 2015 to 2016. HA and HA-PAO peaked in 2021, whereas PAO peaked in 2019. For HA, PAO, and HA-PAO, most cases were performed in female patients and patients aged 30 to 49 years, 10 to 19 years, and 10 to 29 years, respectively. The 5-year incidence of ipsilateral secondary operations, which include revision HA, PAO, or conversion to total hip arthroplasty, was 9.2% (95% confidence interval 8.6%-9.8%) in the HA group and 6.5% (95% confidence interval 4.1%-8.8%) in the PAO group. Combining HA with PAO resulted in so few secondary operations that Kaplan-Meier analysis was infeasible. The PAO cohort had the greatest 30-day emergency visit and 90-day readmission rates, with infection as the most common cause for readmission. Conclusions: HA is more frequently performed than PAO for hip dysplasia. HA-PAO is increasing at the greatest rate, demonstrating fewer complications and reoperations. Level of Evidence: Level III, retrospective comparative trial.
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BACKGROUND: Few theoretically-based, qualitative studies have explored determinants of antimicrobial prescribing behaviour in hospitals. Understanding these can promote successful development and implementation of behaviour change interventions (BCIs). OBJECTIVE: (s): To use the Theoretical Domains Framework (TDF) to explore determinants of clinicians' antimicrobial prescribing behaviour, identifying barriers (i.e., impediments) and facilitators to appropriate antimicrobial practice. METHODS: Semi-structured interviews with purposively-sampled doctors and pharmacists with a wide range of specialties and expertise in Hamad Medical Corporation hospitals in Qatar. Interviews based on previous quantitative research and the TDF were audio-recorded, transcribed and independently analysed by two researchers using the TDF as an initial coding framework. RESULTS: Data saturation was achieved after interviewing eight doctors and eight pharmacists. Inter-related determinants of antimicrobial prescribing behaviour linked to ten TDF domains were identified as barriers and facilitators that may contribute to inappropriate or appropriate antimicrobial prescribing. The main barriers identified were around hospital guidelines and electronic system deficiencies (environmental context and resources); knowledge gaps relating to guidelines and appropriate prescribing (knowledge); restricted roles/responsibilities of microbiologists and pharmacists (professional role and identity); challenging antimicrobial prescribing decisions (memory, attention and decision processes); and professional hierarchies and poor multidisciplinary teamworking (social influences). Key facilitators included guidelines compliance (goals and intentions), and participants' beliefs about the consequences of appropriate or inappropriate prescribing. Further education and training, and some changes to guidelines including their accessibility were also considered essential. CONCLUSIONS: Antimicrobial prescribing behaviour in hospitals is a complex process influenced by a broad range of determinants including specific barriers and facilitators. The in-depth understanding of this complexity provided by this work may support the development of an effective BCI to promote appropriate antimicrobial stewardship.
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Anti-Infecciosos , Médicos , Humanos , Farmacêuticos , Anti-Infecciosos/uso terapêutico , Pesquisa Qualitativa , Prescrição InadequadaRESUMO
STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare patient-reported physical activity between anterior thoracic vertebral body tethering and posterior lumbar spine tethering (ATVBT/PLST) and posterior spinal instrumentation and fusion (PSIF) with minimum 2 year follow-up. METHODS: Consecutive skeletally immature patients with idiopathic scoliosis and a thoracic and lumbar curve magnitude ≥40° who underwent either ATVBT/PLST or PSIF from 2015-2019 were included. The primary outcome was rate of returning to sport. Secondary outcomes included ability to bend and satisfaction with sport performance as well as weeks until return to sport, school, physical education (PE) classes, and running. RESULTS: Ten patients underwent ATVBT/PLST and 12 underwent PSIF. ATVBT/PLST patients reported significantly faster return to sport (13.5 weeks vs 27.9 weeks, P = .04), running (13.3 weeks vs 28.8 weeks, P = .02), and PE class (12.6 weeks vs 26.2 weeks, P = .04) compared to PSIF patients. ATVBT/PLST patients reported that they had to give up activities due to their ability to bend at lower rates than PSIF patients while reporting "no changes" in their ability to bend after surgery at higher rates than PSIF patients (0% vs 4% giving up activities and 70% vs 0% reporting no changes in bending ability for ATVBT/PLST and PSIF, respectively, P = .01). Compared to PSIF patients, ATVBT/PLST patients experienced less main thoracic and thoracolumbar/lumbar curve correction at most recent follow-up (thoracic: 41 ± 19% vs 69 ± 18%, P = .001; thoracolumbar/lumbar: 59 ± 25% vs 78 ± 15%, P = .02). No significant differences in the number of revision surgeries were observed between ATVBT/PLST and PSIF patients (4 (40%) and 1 (8%) for ATVBT/PLST and PSIF, respectively, P = .221). CONCLUSIONS: ATVBT/PLST patients reported significantly faster rates of returning to sport, running, and PE. In addition, ATVBT/PLST patients were less likely to have to give up activities due to bending ability after surgery and reported no changes in their ability to bend after surgery more frequently than PSIF patients. However, the overall rate of return to the same or higher level of sport participation was high amongst both groups, with no significant difference observed between ATVBT/PLST and PSIF patients.