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Abstract Background Pyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Case presentation We report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap. Conclusion This case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available.

Abstract Background There are approximately 8,000 different rare diseases that affect roughly 400 million people worldwide. Many of them suffer from delayed diagnosis. Ciliopathies are rare monogenic disorders characterized by a significant phenotypic and genetic heterogeneity that raises an important challenge for clinical diagnosis. Diagnosis support systems (DSS) applied to electronic health record (EHR) data may help identify undiagnosed patients, which is of paramount importance to improve patients’ care. Our objective was to evaluate three online-accessible rare disease DSSs using phenotypes derived from EHRs for the diagnosis of ciliopathies. Methods Two datasets of ciliopathy cases, either proven or suspected, and two datasets of controls were used to evaluate the DSSs. Patient phenotypes were automatically extracted from their EHRs and converted to Human Phenotype Ontology terms. We tested the ability of the DSSs to diagnose cases in contrast to controls based on Orphanet ontology. Results A total of 79 cases and 38 controls were selected. Performances of the DSSs on ciliopathy real world data (best DSS with area under the ROC curve = 0.72) were not as good as published performances on the test set used in the DSS development phase. None of these systems obtained results which could be described as “expert-level”. Patients with multisystemic symptoms were generally easier to diagnose than patients with isolated symptoms. Diseases easily confused with ciliopathy generally affected multiple organs and had overlapping phenotypes. Four challenges need to be considered to improve the performances: to make the DSSs interoperable with EHR systems, to validate the performances in real-life settings, to deal with data quality, and to leverage methods and resources for rare and complex diseases. Conclusion Our study provides insights into the complexities of diagnosing highly heterogenous rare diseases and offers lessons derived from evaluation existing DSSs in real-world settings. These insights are not only beneficial for ciliopathy diagnosis but also hold relevance for the enhancement of DSS for various complex rare disorders, by guiding the development of more clinically relevant rare disease DSSs, that could support early diagnosis and finally make more patients eligible for treatment.

Abstract Background Amid the current burden of non-communicable (NCD) diseases in Malaysia, there is a growing demand for more efficient service delivery of primary healthcare. A complex intervention is proposed to improve NCD management in Malaysia. This exploratory study aimed to assess primary healthcare providers’ receptiveness towards change prior to implementation of the proposed complex intervention. Method This study was conducted using an exploratory qualitative approach on purposely selected healthcare providers at primary healthcare clinics. Twenty focus group discussions and three in-depth interviews were conducted using a semi-structured interview guide. Consent was obtained prior to interviews and for audio-recordings. Interviews were transcribed verbatim and thematically analysed, guided by the Consolidated Framework for Implementation Research (CFIR), a framework comprised of five major domains promoting implementation theory development and verification across multiple contexts. Results The study revealed via CFIR that most primary healthcare providers were receptive towards any proposed changes or intervention for the betterment of NCD care management. However, many challenges were outlined across four CFIR domains—intervention characteristics, outer setting, inner setting, and individual characteristics—that included perceived barriers to implementation. Perception of issues that triggered proposed changes reflected the current situation, including existing facilitating aspects that can support the implementation of any future intervention. The importance of strengthening the primary healthcare delivery system was also expressed. Conclusion Understanding existing situations faced at the primary healthcare setting is imperative prior to implementation of any intervention. Healthcare providers’ receptiveness to change was explored, and using CFIR framework, challenges or perceived barriers among healthcare providers were identified. CFIR was able to outline the clinics’ setting, individual behaviour and external agency factors that have direct impact to the organisation. These are important indicators in ensuring feasibility, effectiveness and sustainability of any intervention, as well as future scalability considerations.