Italian national consensus statement on management and pharmacological treatment of phenylketonuria

Background Phenylketonuria (PKU) is a rare inherited metabolic disorder caused by defects in the phenylalanine-hydroxylase gene (PAH), the enzyme catalyzing the conversion of phenylalanine to tyrosine. PAH impairment causes phenylalanine accumulation in the blood and brain, with a broad spectrum of pathophysiological and neurological consequences for patients. Prevalence of disease varies, with peaks in some regions and countries, including Italy. A recent expert survey described the real-life of clinical practice for PKU in Italy, revealing inhomogeneities in disease management, particularly concerning approach to pharmacotherapy with sapropterin hydrochloride, analogous of the natural PAH co-factor, allowing disease control in a subset of patients. Therefore, the purpose of this paper is to continue the work initiated with the expert survey paper, to provide national guidances aiming to harmonize and optimize patient care at a national level. Participants The Consensus Group, convened by 10 Steering Committee members, consisted of a multidisciplinary crowd of 46 experts in the management of PKU in Italy. Consensus process The Steering Committee met in a series of virtual meeting in order to discuss on clinical focuses to be developed and analyzed in guidance statements, on the basis of expert practice based evidence, large systematic literature review previously performed in the expert survey paper, and evidence based consensus published. Statements were re-discussed and refined during consensus conferences in the widest audience of experts, and finally submitted to the whole consensus group for a modified-Delphi voting. Results Seventy three statements, divided in two main clinical areas, PKU management and Pharmacotherapy, achieved large consensus in a multidisciplinary group of expert in different aspects of disease. Importantly, these statements involve guidances for the use of sapropterin dihydrochloride, still not sufficiently implemented in Italy, and a set of good practice to approach the use of novel enzyme replacement treatment pegvaliase. Conclusions This evidence-based consensus provides a minimum set of guidances for disease management to be implemented in all PKU centers. Moreover, these guidances represent the first statement for sapropterin dihydrochloride use, implementation and standardization in Italy, and a guide for approaching pegvaliase treatment at a national level on a consistent basis.

The revision partial knee classification system: understanding the causative pathology and magnitude of further surgery following partial knee arthroplasty

Aims Joint registries classify all further arthroplasty procedures to a knee with an existing partial arthroplasty as revision surgery, regardless of the actual procedure performed. Relatively minor procedures, including bearing exchanges, are classified in the same way as major operations requiring augments and stems. A new classification system is proposed to acknowledge and describe the detail of these procedures, which has implications for risk, recovery, and health economics. Methods Classification categories were proposed by a surgical consensus group, then ranked by patients, according to perceived invasiveness and implications for recovery. In round one, 26 revision cases were classified by the consensus group. Results were tested for inter-rater reliability. In round two, four additional cases were added for clarity. Round three repeated the survey one month later, subject to inter- and intrarater reliability testing. In round four, five additional expert partial knee arthroplasty surgeons were asked to classify the 30 cases according to the proposed revision partial knee classification (RPKC) system. Results Four classes were proposed: PR1, where no bone-implant interfaces are affected; PR2, where surgery does not include conversion to total knee arthroplasty, for example, a second partial arthroplasty to a native compartment; PR3, when a standard primary total knee prosthesis is used; and PR4 when revision components are necessary. Round one resulted in 92% inter-rater agreement (Kendall’s W 0.97; p < 0.005), rising to 93% in round two (Kendall’s W 0.98; p < 0.001). Round three demonstrated 97% agreement (Kendall’s W 0.98; p < 0.001), with high intra-rater reliability (interclass correlation coefficient (ICC) 0.99; 95% confidence interval 0.98 to 0.99). Round four resulted in 80% agreement (Kendall’s W 0.92; p < 0.001). Conclusion The RPKC system accounts for all procedures which may be appropriate following partial knee arthroplasty. It has been shown to be reliable, repeatable and pragmatic. The implications for patient care and health economics are discussed. Cite this article: Bone Jt Open 2021;2(8):638–645.

Proof-of-Reputation: An Alternative Consensus Mechanism for Blockchain Systems

Blockchains combine other technologies, such as cryptography, networking, and incentive mechanisms, to enable the creation, validation, and recording of transactions between participating nodes. A consensus algorithm is used in a blockchain system to determine the shared state among distributed nodes. An important component underlying any blockchain-based system is its consensus mechanism, which principally determines the performance and security of the overall system. As the nature of peer-topeer(P2P) networks is open and dynamic, the security risk within that environment is greatly increased mostly because nodes can join and leave the network at will. Thus, it is important to have a system that can check against malicious behaviour. In this work, we propose a reputation-based consensus mechanism for blockchain-based systems, Proof-of-Reputation(PoR) where the nodes with the highest reputation values eventually become part of a consensus group that determines the state of the blockchain.

An Interrater Reliability Study on the Gothenburg Obstetric Triage System- a New Obstetric Triage System

Background Triage, identifying patients with critical and time-sensitive disorders, is an integrated process in general emergency medicine. Obstetric triage is more specialised, requiring assessment of both woman, fetus and labour status. Failure to identify severely ill obstetric patients has repeatedly led to maternal morbidity and mortality. Reliable triage systems, adapted to obstetric patients as well as local conditions, are thus essential. The study aims to assess the interrater reliability (IRR) of the Gothenburg Obstetric Triage System (GOTS). Methods Midwives (n=6) and registered nurses with no experience in managing obstetric patients (n=7), assessed 30 paper cases based on actual real-life cases, using the GOTS. Furthermore, a consensus group consisting of two midwives and two obstetricians, with extensive experience in obstetric care, determined the correct triage level in order to enable analysis of over- and undertriage. IRR was assessed, both with percentage of absolute agreement and with intra-class correlation coefficients (ICC) with 95% confidence intervals (CI). Results A total of 418 assessments were performed, comprising all five levels of acuity in the GOTS. Absolute agreement was found in 69.6% of the assessments. The overall IRR was good, with a Kappa value of 0.78 (0.69 – 0.87, 95% CI) for final triage level. Comparison with consensus group assessments established that over- and undertriage had occurred in 9% and 21% of the cases, respectively. The main reasons for undertriage were “not acknowledging abnormal vital sign parameters” and “limitations in study design”. Conclusion The GOTS is a reliable tool for triaging obstetric patients. It enables a standardized triage process unrelated to the assessors’ level of experience in assessing and managing obstetric patients and is applicable for triaging obstetric patients presenting for emergency care at obstetric or emergency units.

Innovative collaborative instructional strategies: it’s effect on secondary school students’ achievement in biology as moderated by verbal ability

Education is changing rapidly. Schools are gradually shifting away from the traditional mode of instruction and toward a more active model of learning, in which students are collaborating on projects in small groups and then sharing their work with the class. Africa cannot afford to be left behind in this change. Though collaborative teaching and learning are quite popular in Africa, its variants/forms, consensus group and cooperative reflective journal writing are not. The effect of collaborative instructional strategies (consensus group and cooperative reflective journal writing) on students' achievement in biology as moderated by verbal ability was determined in this study. Three hundred five senior secondary school II students from two local governments' area within Ibadan Metropolis participated in the study. The Students' Biology Achievement Test (SBAT) and the Students' Verbal Ability Test (SVAT) were the main data collection tools used for this study. Data generated were analysed using Analysis of Covariance (ANCOVA) and Bonferonni post hoc test. Results show that both forms of collaborative instructional strategies improved students' achievement in biology. Results showed that students exposed to the cooperative reflective journal writing achieved more in biology followed by students in the consensus group strategy. Collaborative strategy can be a feasible alternative approach to teaching biology as it fairly addresses issues of interaction in the classroom. This has helped students develop their communication and also improve their socialisation skills in the classroom and beyond.