Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope.

Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. Management of patients with PH and kidney failure is also extremely challenging. However, in the past few years, several new developments, including new outcome data from patients with infantile oxalosis, from transplanted patients with type 1 PH (PH1) and from patients with the rarer PH types 2 and 3, have emerged. In addition, two promising therapies based on RNA interference have been introduced. These developments warrant an update of existing guidelines on PH, based on new evidence and on a broad consensus. In response to this need, a consensus development core group, comprising (paediatric) nephrologists, (paediatric) urologists, biochemists and geneticists from OxalEurope and the European Rare Kidney Disease Reference Network (ERKNet), formulated and graded statements relating to the management of PH on the basis of existing evidence. Consensus was reached following review of the recommendations by representatives of OxalEurope, ESPN, ERKNet and ERA, resulting in 48 practical statements relating to the diagnosis and management of PH, including consideration of conventional therapy (conservative therapy, dialysis and transplantation), new therapies and recommendations for patient follow-up.

Recommendations of the International Medical Informatics Association (IMIA) on Education in Biomedical and Health Informatics: Second Revision.

BACKGROUND: The purpose of educational recommendations is to assist in establishing courses and programs in a discipline, to further develop existing educational activities in the various nations, and to support international initiatives for collaboration and sharing of courseware. The International Medical Informatics Association (IMIA) has published two versions of its international recommendations in biomedical and health informatics (BMHI) education, initially in 2000 and revised in 2010. Given the recent changes to the science, technology, the needs of the healthcare systems, and the workforce of BMHI, a revision of the recommendations is necessary. OBJECTIVE: The aim of these updated recommendations is to support educators in developing BMHI curricula at different education levels, to identify essential skills and competencies for certification of healthcare professionals and those working in the field of BMHI, to provide a tool for evaluators of academic BMHI programs to compare and accredit the quality of delivered programs, and to motivate universities, organizations, and health authorities to recognize the need for establishing and further developing BMHI educational programs. METHOD: An IMIA taskforce, established in 2017, updated the recommendations. The taskforce included representatives from all IMIA regions, with several having been involved in the development of the previous version. Workshops were held at different IMIA conferences, and an international Delphi study was performed to collect expert input on new and revised competencies. RESULTS: Recommendations are provided for courses/course tracks in BMHI as part of educational programs in biomedical and health sciences, health information management, and informatics/computer science, as well as for dedicated programs in BMHI (leading to bachelor's, master's, or doctoral degree). The educational needs are described for the roles of BMHI user, BMHI generalist, and BMHI specialist across six domain areas - BMHI core principles; health sciences and services; computer, data and information sciences; social and behavioral sciences; management science; and BMHI specialization. Furthermore, recommendations are provided for dedicated educational programs in BMHI at the level of bachelor's, master's, and doctoral degrees. These are the mainstream academic programs in BMHI. In addition, recommendations for continuing education, certification, and accreditation procedures are provided. CONCLUSION: The IMIA recommendations reflect societal changes related to globalization, digitalization, and digital transformation in general and in healthcare specifically, and center on educational needs for the healthcare workforce, computer scientists, and decision makers to acquire BMHI knowledge and skills at various levels. To support education in BMHI, IMIA offers accreditation of quality BMHI education programs. It supports information exchange on programs and courses in BMHI through its Working Group on Health and Medical Informatics Education.

Speed of facial affect intensity recognition as an endophenotype of first-episode psychosis and associated limbic-cortical grey matter systems.

BACKGROUND: Psychotic disorders are highly heritable such that the unaffected relatives of patients may manifest characteristics, or endophenotypes, that are more closely related to risk genes than the overt clinical condition. Facial affect processing is dependent on a distributed cortico-limbic network that is disrupted in psychosis. This study assessed facial affect processing and related brain structure as a candidate endophenotype of first-episode psychosis (FEP). METHOD: Three samples comprising 30 FEP patients, 30 of their first-degree relatives and 31 unrelated healthy controls underwent assessment of facial affect processing and structural magnetic resonance imaging (sMRI) data. Multivariate analysis (partial least squares, PLS) was used to identify a grey matter (GM) system in which anatomical variation was associated with variation in facial affect processing speed. RESULTS: The groups did not differ in their accuracy of facial affect intensity rating but differed significantly in speed of response, with controls responding faster than relatives, who responded faster than patients. Within the control group, variation in speed of affect processing was significantly associated with variation of GM density in amygdala, lateral temporal cortex, frontal cortex and cerebellum. However, this association between cortico-limbic GM density and speed of facial affect processing was absent in patients and their relatives. CONCLUSIONS: Speed of facial affect processing presents as a candidate endophenotype of FEP. The normal association between speed of facial affect processing and cortico-limbic GM variation was disrupted in FEP patients and their relatives.

Computerized cognitive remediation training for schizophrenia: an open label, multi-site, multinational methodology study.

A recent single-site study (Fisher et al., 2009. Am J Psychiatry. 166 (7) 805-11) showed that repeated training with the Brain Fitness Program (BFP) improved performance on a battery of neuropsychological tasks. If replicated these data suggest an important non-pharmacological method for ameliorating cognitive impairment in schizophrenia. Our study evaluated the BFP training effects in an open-label, multi-site, multinational clinical trial. Fifty-five stable adult patients with schizophrenia on regular antipsychotic medication completed ≥ 32 BFP training sessions over 8-10 weeks. Training effects on cognitive performance and functional capacity outcome measures were measured using CogState® schizophrenia battery, UCSD Performance based Skills Assessment (UPSA-2) and Cognitive Assessment Interview (CAI). BFP training showed a large and significant treatment effect on a training exercise task (auditory processing speed), however this effect did not generalize to improved performance on independent CogState® assessment. There were no significant effects on UPSA-2 or CAI scores. Our study demonstrated the feasibility of implementing BFP training in a multi-site study. However, BFP training did not show significant treatment effects on cognitive performance or functional capacity outcome measures despite showing large and significant effects on a training exercise.

Colorectal cancer patients' attitudes towards involvement in decision making.

OBJECTIVES: To design and administer an attitude rating scale, exploring colorectal cancer patients' views of involvement in decision making. To examine the impact of socio-demographic and/or treatment-related factors on decision making. To conduct principal components analysis to determine if the scale could be simplified into a number of factors for future clinical utility. METHODS: An attitude rating scale was constructed based on previous qualitative work and administered to colorectal cancer patients using a cross-sectional survey approach. RESULTS: 375 questionnaires were returned (81.7% response). For patients it was important to be informed and involved in the decision-making process. Information was not always used to make decisions as patients placed their trust in medical expertise. Women had more positive opinions on decision making and were more likely to want to make decisions. Written information was understood to a greater degree than verbal information. The scale could be simplified to a number of factors, indicating clinical utility. CONCLUSION: Few studies have explored the attitudes of colorectal cancer patients towards involvement in decision making. This study presents new insights into how patients view the concept of participation; important when considering current policy imperatives in the UK of involving service users in all aspects of care and treatment.

An unusual N-terminal deletion of the laminin alpha3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome.

Laryngo-onycho-cutaneous (LOC or Shabbir) syndrome (OMIM 245660) is an autosomal recessive epithelial disorder confined to the Punjabi Muslim population. The condition is characterized by cutaneous erosions, nail dystrophy and exuberant vascular granulation tissue in certain epithelia, especially conjunctiva and larynx. Genome-wide homozygosity mapping localized the gene to a 2 Mb region on chromosome 18q11.2 with an LOD score of 19.8 at theta=0. This region includes the laminin alpha3 gene (LAMA3), in which loss-of-expression mutations cause the lethal skin blistering disorder Herlitz junctional epidermolysis bullosa. Detailed investigation showed that this gene possesses a further 38 exons (76 exons in total) spanning 318 kb of genomic DNA, and encodes three distinct proteins, designated laminin alpha3a, alpha3b1 and alpha3b2. The causative mutation in 15 families was a frameshift mutation 151insG predicting a stop codon 7 bp downstream in an exon that is specific to laminin alpha3a. This protein is secreted only by the basal keratinocytes of stratified epithelia, implying that LOC is caused by dysfunction of keratinocyte-mesenchymal communication. Surprisingly, the 151insG mutation does not result in nonsense-mediated mRNA decay due to rescue of the transcript by an alternative translation start site 6 exons downstream. The resultant N-terminal deletion of laminin alpha3a was confirmed by immunoprecipitation of secreted proteins from LOC keratinocytes. These studies show that the laminin alpha3a N-terminal domain is a key regulator of the granulation tissue response, with important implications not only in LOC but in a range of other clinical conditions associated with abnormal wound healing.