National surveys to evaluate prescribing practices: Methodological considerations

With the changing healthcare landscape, evaluating the care provision in ambulatory settings is vital to understand outpatient care. The national surveys such as the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) are valuable resources to pharmacy researchers because of their availability and generalizability. With the recent focus on real-world data, the national surveys are critical in providing practice and policy evidence by evaluating ambulatory care, especially prescribing practices. The use of these surveys requires an understanding of the survey content, scope, complex sampling scheme, and analytical and research considerations. There are several methodological and practical considerations that make these national surveys useful to both novice and seasoned researchers. Although some generalized approaches are available for analyzing the national surveys, there is limited focus on the NAMCS and the NHAMCS. This paper provides an in-depth understanding of the NAMCS/NHAMCS, including methodological considerations for evaluating prescribing practices in ambulatory settings.     

Repurposing of parenterally administered active substances used to treat pain both systemically and locally

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.     

Correction results of atypical clubfeet managed with modified Ponseti technique: A meta-analysis of 354 feet

Background/purposeAtypical clubfeet are distinct from idiopathic clubfeet. It is resistant to correction by conventional casting methods and often requires a modification of Ponseti's casting technique. Although the initial correction rates are reasonable, relapse and complications are frequent. There is limited literature on the results of modified Ponseti casting of these feet. We conducted this meta-analysis to study a few important aspects of atypical/complex clubfeet treatment by the modified Ponseti technique.Research questionWhat are the results of atypical or complex clubfeet after treatment by the modified Ponseti technique?MethodologyFive electronic databases (PubMed, Embase, Scopus, Ovid, and Cochrane Library) were searched for articles reporting on the results of atypical/complex clubfeet treated by the modified Ponseti technique. Details of the number of casts required for correction, rate of percutaneous Achilles tenotomy (PAT), other soft tissue procedures required, complications, and relapse rates were extracted into spreadsheets, and meta-analysis was carried out using OpenMeta Analyst software.ResultsTen studies were included for analysis with a total of 240 patients with 354 clubfeet. The initial correction was achieved in all feet. A pooled analysis of the data showed that a mean of six casts was required for the initial correction. The rate of PAT was 98.3%. The overall complication rate was 16.8%. 7.2% required an additional soft tissue procedure apart from the PAT, and relapse of the deformity was observed in a mean of 19.8% cases.ConclusionModified Ponseti technique is effective in the initial management of atypical/complex clubfeet. Although the PAT rate is slightly higher in the Modified Ponseti technique, the remaining result parameters are comparable with the results of idiopathic clubfoot managed with the Ponseti method of casting. However, these children should be kept under follow-up for a longer duration to find the exact relapse rates.     

Practice developments supporting change implementation in Wellington,New Zealand (NZ) for ‘continuity of care when transitioning complex preterm infants from NICU to home’

The discussion paper will focus on continuity of care relating to previous NZ research, specifically to transitioning complex preterm infants from NICU to home based on parent experiences, and on the practice developments that have occurred, to ensure optimal health outcomes. Previous NZ research discovered parent desire a consistent service delivery for the entire transition journey from NICU and at home.An informative and comprehensive opportunity has occurred for reflective professional practice, evaluation, development and implementation which have transpired in positive change through innovative practice developments and support change implementation in Wellington, NZ. This has resulted in the articulation of a model of care that has both embraced and integrated parental desires for a continuity of care process for complex preterm infants. This has been achieved by having the same Discharge Facilitator/Key Case Manager present within the NICU and external to the NICU for Home-based infants for the entire transition journey.The paper will focus and emphasis additional practice development changes and furthermore, will present a real purpose, for other countries to learn of such practice developments that have exemplified a celebratory success for families of Wellington, NZ.     

COX20基因变异线粒体复合物Ⅳ缺乏症相关的遗传性周围神经病4例病例系列报告及文献复习

背景：原发性线粒体病具有高度的临床和遗传异质性，其中周围神经是线粒体病的常见受累器官之一。 目的：总结COX20基因变异相关周围神经病的临床表型及遗传学特征。 设计：病例系列报告。 方法：回顾性收集2018年5月至2020年5月复旦大学附属儿科医院诊治的COX20基因变异相关周围神经病患儿的临床资料，总结其临床表现、基因检测结果及治疗效果，并以“COX20”、“线粒体复合物Ⅳ缺乏症（Complex Ⅳ deficiency）”为关键词检索中英文数据库。检索时间均为从建库至2021年12月。总结已报道COX20基因变异与临床表型的关系。 主要结局指标：临床表型和COX20基因变异位点。 结果：4例患儿纳入分析，男、女各2例，其中3例自幼运动发育落后。4例均在儿童期起病，均以行走不稳为首发症状。肌电图均提示多发性周围神经损害改变，感觉神经轴索受累为主。4例患儿均携带COX20基因复合杂合变异，包括错义变异2个，无义变异和移码变异各1个，其中移码变异c.262delG(p.E88Kfs*35)尚未见报道。文献复习目前共报道COX基因变异18个家系22例患儿（包括本文病例）,起病中位年龄为5（1.0~17）岁，22例均以行走困难或步态不稳起病，11例（50.0%）有精神运动发育迟滞，病程中14例(63.6%)出现构音障碍，14例(63.6%)出现肌力下降和/或足部畸形，8例（36.4%）出现共济失调，6例(27.3%)出现肌张力障碍，5例（22.7%）存在认知倒退等。21例患儿行神经传导及肌电图检查，19例(90.5%)提示多发性周围神经病变。头颅（18例）及脊髓（10例）MR检查提示，脊髓萎缩4例（40%），小脑萎缩4例（22.2%）。9例患儿已无法独立行走，丧失独立行走能力中位年龄为10（7~21）岁。目前共报道9个变异位点，4种变异类型，其中错义变异5个，剪切变异2个，无义变异和移码变异各1个。 结论：COX20基因变异患者多早期起病，以周围神经系统病变为主要表现，可合并构音障碍、共济失调、肌张力障碍、认知倒退等，病情逐渐进展，致残率高。COX20基因变异类型以错义变异最常见。     

3D打印骨折模型在复杂骨盆骨折手术中的治疗方法及效果探讨

目的:探讨复杂骨盆骨折手术治疗中3D打印骨折模型的应用方法及效果。方法:选取医院收治的60例复杂骨盆骨折患者,按照随机数表法将其分为对照组和观察组,每组30例。对照组行传统CT指导下手术治疗,观察组行3D打印仿真骨盆模型体外模拟术后,应用腹直肌旁切口钢板内固定术治疗。比较两组手术时间、住院时间和骨折愈合时间,以及术中出血量、并发症发生率和骨盆功能恢复优良率。结果:观察组手术时间、住院时间及骨折愈合时间短于对照组,术中出血量少于对照组,差异有统计学意义(t=2.721,t=2.458,t=2.791,t=4.450;P<0.05);观察组和对照组并发症发生率分别为3.33%和10.00%,差异无统计学意义(x²=0.267,P>0.05);观察组和对照组骨盆功能恢复优良率分别为96.67%和73.33%,观察组明显高于对照组,差异有统计学意义(x²=4.705,P<0.05)。结论:复杂骨盆骨折手术中应用3D打印骨折模型可缩短手术时间、住院时间,减少出血量,促进骨折愈合,可改善骨盆功能且并发症少。     

Visual fixations and visually induced dizziness: An exploratory study

BackgroundVisually induced dizziness can develop as a sequala of a vestibular disorder and is characterized by symptoms of nausea, dizziness, and imbalance in rich visual environments such as supermarkets and shopping malls. To date the mechanisms underlying visually induced dizziness are poorly understood.Research questionWhat are the characteristics of visual fixations and postural sway in adults with visually induced dizziness compared to healthy adults when exposed to increasingly complex visual environments?MethodsWe recruited 20 adults with visually induced dizziness and 20 healthy adults to this cross-sectional exploratory study. Participants were instructed to maintain gaze on letters projected on a large screen with backgrounds of differing visual complexity. The number of visual refixations, movement of the centre of pressure, and movement of the head and body centres of mass were recorded.ResultsAdults with visually induced dizziness showed a significantly higher number of visual refixations (F= 10.592, p < 0.01), and increased mean velocity of head and body centres of mass movement (F= 14.034, p < 0.01 and F= 6.553, p < 0.05 respectively) compared to healthy adults.SignificanceAdults with visually induced dizziness exhibited visual fixational instability and increased postural and head sway compared to healthy adults. This was mainly observed in conditions with complex and moving backgrounds. This may account for reports from adults with visually induced dizziness of worsening symptoms in busy environments. The results from the study may assist in guiding intervention development to reduce symptoms of visually induced dizziness.     

Neuroimaging the pain network – Implications for treatment

In this chapter, we provide an overview of neuroimaging studies in chronic pain. We start with an introduction about the phenomenology of pain. In the following section, the application of functional and structural imaging techniques is shown in selected chronic pain syndromes (chronic back pain, fibromyalgia syndrome (FMS), phantom limb pain, and complex regional pain syndrome (CRPS)), and commonalities and peculiarities of imaging correlates across different types of chronic pain are discussed. We conclude this chapter with implications for treatments, with focus on behavioral interventions, sensory and motor trainings, and mirror and motor imagery trainings.     

A prognostic signature based on immune-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the fourth commonest female malignancy worldwide. CESC progresses in immune-microenvironment mainly composed of infiltrating immune and stromal cells. Here, we performed an integrated analysis incorporating the expression profiles from the Cancer Genome Atlas (TCGA) database and scores of immune and stromal cells calculated by Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm. A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC. Based on this signature, patients were divided into the high- and low-risk groups, and this signature showed good prognostic performance according to the results of Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis in train set and two validation sets. A nomogram was built for evaluating the clinical applicability of this signature. In addition, based on Tumor Immune Estimation Resource (TIMER) database, 2 hub genes showed negative correlations with tumor purity and positive correlations with infiltrating levels of immune filtrating cells. What’s more, we propose new treatment strategies for the two prognostic subtypes. Low- risk patients were found presenting with a higher level of immune checkpoint molecules and showing higher immunogenicity in immunophenoscore (IPS) analysis, which indicated a better response for immunotherapy. Meanwhile, estimated by Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk patients showed sensitive responses to five chemotherapy drugs. Finally, 10 candidate small-molecule drugs for CESC were defined. In summary, the CD1C-CD6 signature can accurately predict the prognosis of CESC.