Optimizing paediatric specialist referrals for short stature in an era of multiple growth hormone indications.

The assessment of growth during infancy and childhood is an essential component of paediatric medicine, as atypical growth may point to the existence of an underlying health condition. To reduce morbidity, it is vital that treatment for growth disorders is provided in a timely fashion. However, although there are guidelines regarding referral criteria for short stature in Europe and the USA, there are no such guidelines in Canada. To address this, a series of consultations and workshops with paediatricians, paediatric endocrinologists, family physicians and nurses were held, with the aim of developing a consensus-based set of recommendations for children in Canada showing atypical growth and to identify red flags for children who might benefit from early referral. To achieve this, a referral algorithm and referral form for primary care providers were developed to ensure timely and appropriate referrals, and transmission of the most relevant details to the secondary care consultant.

Long-term symptom severity and clinical biomarkers in post-COVID-19/chronic fatigue syndrome: results from a prospective observational cohort.

Background: Post-COVID-19 syndrome (PCS) is characterised by a wide range of symptoms, primarily fatigue and exertion intolerance. While disease courses in the early months post-infection have been well-described, the long-term health consequences for patients with PCS with disabling fatigue remain unclear. Methods: In this prospective observational cohort study, we evaluated symptom severity and various biomarkers, including hand grip strength (HGS), cardiovascular function, and laboratory parameters, in 106 patients with PCS with moderate to severe fatigue and exertion intolerance at three time points after infection (3-8, 9-16, and 17-20 months). The study was conducted at the Charité's Fatigue Centre and the Charité's outpatient clinic for neuroimmunology at Berlin, Germany from July 16, 2020, to February 18, 2022. A subset of patients (PCS-ME/CFS) met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome according to the Canadian Consensus Criteria (CCC). The aim was to determine differences in the disease course between the two patient groups (i.e., PCS vs PCS-ME/CFS) and identify correlating biomarkers. Findings: Patients with PCS-ME/CFS reported persistently high severity of most symptoms up to 20 months after infection, while patients with PCS showed overall health improvement. Although fatigue and post-exertional malaise (PEM), hallmarks of post-infectious fatigue syndromes, were still evident in both groups, they remained more pronounced in PCS-ME/CFS. Inflammatory biomarkers decreased in both groups, but not antinuclear antibodies. Lower HGS at onset correlated with symptom persistence, particularly in patients with PCS-ME/CFS. Interpretation: Our findings suggest that PCS can persist beyond 20 months post-infection and encompass the full scope of post-infectious ME/CFS as defined by the CCC. Sub-classifying patients with PCS based on the CCC can assist in the management and monitoring of patients with PCS-ME/CFS due to their persistently higher symptom severity. Funding: C. S. was supported by a grant from the Weidenhammer-Zoebele Foundation. F. K. was supported by the Volkswagen Foundation.

Updated Canadian Expert Consensus on Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease.

PURPOSE: The purpose of this article is to update the previously published consensus recommendations from March 2017 discussing the optimal management of adult patients with autosomal dominant polycystic kidney disease (ADPKD). This document focuses on recent developments in genetic testing, renal imaging, assessment of risk regarding disease progression, and pharmacological treatment options for ADPKD. SOURCES OF INFORMATION: Published literature was searched in PubMed, the Cochrane Library, and Google Scholar to identify the latest evidence related to the treatment and management of ADPKD. METHODS: All pertinent articles were reviewed by the authors to determine if a new recommendation was required, or if the previous recommendation needed updating. The consensus recommendations were developed by the authors based on discussion and review of the evidence. KEY FINDINGS: The genetics of ADPKD are becoming more complex with the identification of new and rarer genetic variants such as GANAB. Magnetic resonance imaging (MRI) and computed tomography (CT) continue to be the main imaging modalities used to evaluate ADPKD. Total kidney volume (TKV) continues to be the most validated and most used measure to assess disease progression. Since the publication of the previous consensus recommendations, the use of the Mayo Clinic Classification for prognostication purposes has been validated in patients with class 1 ADPKD. Recent evidence supports the benefits of a low-osmolar diet and dietary sodium restriction in patients with ADPKD. Evidence from the Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trial supports the use of ADH (antidiuretic hormone) receptor antagonism in patients with ADPKD 18 to 55 years of age with eGFR (estimated glomerular filtration rate) of 25 to 65 mL/min/1.73 m2 or 56 to 65 years of age with eGFR of 25 to 44 mL/min/1.73 m2 with historical evidence of a decline in eGFR >2.0 mL/min/1.73 m2/year. LIMITATIONS: Available literature was limited to English language publications and to publications indexed in PubMed, the Cochrane Library, and Google Scholar. IMPLICATIONS: Advances in the assessment of the risk of disease progression include the validation of the Mayo Clinic Classification for patients with class 1 ADPKD. Advances in the pharmacological management of ADPKD include the expansion of the use of ADH receptor antagonism in patients 18 to 55 years of age with eGFR of 25 to 65 mL/min/1.73 m2 or 56 to 65 years of age with eGFR of 25 to 44 mL/min/1.73 m2 with historical evidence of a decline in eGFR >2.0 mL/min/1.73 m2/year, as per the results of the REPRISE study.

MOTIF: L'objet de cet article est de faire une mise à jour des recommandations consensuelles publiées en mars 2017 traitant de la prise en charge des patients adultes atteints de la maladie polykystique autosomique dominante (MPAD). Ce document s'intéresse aux développements récents en matière de dépistage génétique, d'imagerie rénale, d'évaluation des risques de progression de la maladie et des options de traitement pharmacologique de la MPAD. SOURCES: Les plus récents développements liés à la prise en charge et au traitement de la MPAD ont été colligés à partir des articles publiés sur le sujet dans PubMed, la bibliothèque Cochrane et Google Scholar. MÉTHODOLOGIE: Les auteurs ont relu tous les articles pertinents pour déterminer si de nouvelles recommandations étaient requises ou si les recommandations ultérieures nécessitaient une mise à jour. Les recommandations consensuelles ont été élaborées par les auteurs à partir de la discussion et de la révision des données probantes. PRINCIPAUX RÉSULTATS: Les caractéristiques génétiques de la MPAD deviennent de plus en plus complexes avec l'identification de nouvelles et de plus rares variantes telles que GANAB. L'IRM et la tomodensitométrie demeurent les principales modalités d'imagerie utilisées pour le diagnostic et l'évaluation de la MPAD. Le volume rénal total (VRT) continue d'être la mesure la mieux validée et la plus employée pour évaluer la progression de la maladie. Depuis la publication des précédentes recommandations consensuelles, le recours à la classification de la Clinique Mayo a été validé à des fins pronostiques chez les patients atteints de MPAD de type 1. Des données récentes soutiennent les bienfaits d'une diète à faible osmolarité et des restrictions alimentaires pour le sodium chez les patients atteints de la MPAD. Les résultats de l'essai REPRISE (Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD) viennent appuyer le recours à des antagonistes des récepteurs de l'ADH chez les patients atteints de la MPAD âgés de 18 à 55 ans et dont le DFGe se situe entre 25 et 65 mL/min/1,73 m2 ou chez ceux qui sont âgés de 56 à 65 ans et dont le DFGe se situe entre 25 et 44 mL/min/1,73 m2 et dont les antécédents montrent un déclin du DFGe supérieur à 2,0 mL/min/1,73 m2 par année. LIMITES: La recherche s'est limitée aux publications en anglais et indexées sur PubMed, Google Scholar et dans la bibliothèque Cochrane. IMPLICATIONS: Les avancées dans l'évaluation du risque de progression de la maladie incluent la validation de la classification de la clinique Mayo pour les patients atteints de MPAD de type 1. Les développements dans la prise en charge pharmacologique de la MPAD incluent les résultats obtenus lors de l'essai REPRISE; soit l'élargissement de l'utilisation des antagonistes des récepteurs de l'ADH aux patients âgés de 18 à 25 ans dont le DFGe se situe entre 25 et 65 mL/min/1,73 m2 ou à ceux âgés de 56 à 65 ans dont le DFGe se situe entre 25 et 44 mL/min/1,73 m2 et dont les antécédents montrent un déclin du DFGe supérieur à 2,0 mL/min/1,73 m2 par année.

Diagnosis and management of gastrointestinal neuroendocrine tumors: An evidence-based Canadian consensus.

The majority of neuroendocrine tumors originate in the digestive system and incidence is increasing within Canada and globally. Due to rapidly evolving evidence related to diagnosis and clinical management, updated guidance on the diagnosis and treatment of gastrointestinal neuroendocrine tumors (GI-NETs) are of clinical importance. Well-differentiated GI-NETs may exhibit indolent clinical behavior and are often metastatic at diagnosis. Some NET patients will develop secretory disease requiring symptom control to optimize quality of life and clinical outcomes. Optimal management of GI-NETs is in a multidisciplinary environment and is multimodal, requiring collaboration between medical, surgical, imaging and pathology specialties. Clinical application of advances in pathological classification and diagnostic technologies, along with evolving surgical, radiotherapeutic and medical therapies are critical to the advancement of patient care. We performed a systematic literature search to update our last set of published guidelines (2010) and identified new level 1 evidence for novel therapies, including telotristat etiprate (TELESTAR), lanreotide (CLARINET), everolimus (RADIANT-2; RADIANT-4) and peptide receptor radionuclide therapy (PRRT; NETTER-1). Integrating these data with the clinical knowledge of 16 multi-disciplinary experts, we devised consensus recommendations to guide state of the art clinical management of GI-NETs.

Ending overly broad HIV criminalization: Canadian scientists and clinicians stand for justice.

In Canada, people living with HIV who do not disclose their HIV status prior to sexual acts risk prosecution for aggravated sexual assault even if they have sex with a condom or while having a low (or undetectable) viral load, they had no intent to transmit HIV, and no transmission occurred. In 2013, six distinguished Canadian HIV scientists and clinicians took ground-breaking action to advance justice by co-authoring the "Canadian consensus statement on HIV and its transmission in the context of the criminal law." This effort was born out of the belief that the application of criminal law to HIV non-disclosure was being driven by a poor appreciation of the science of HIV. More than 75 HIV scientists and clinicians Canada-wide have now endorsed the statement, agreeing that "[they] have a professional and ethical responsibility to assist those in the criminal justice system to understand and interpret current medical and scientific evidence regarding HIV." As some 61 countries have adopted laws that specifically allow for HIV criminalization, and prosecutions for HIV non-disclosure, exposure and transmission have been reported in at least 49 countries, the authors hope that others around the world will take similar action.

Diagnosis and management of Alzheimer's disease: past, present and future ethical issues.

There is great interest in the ethical issues associated with Alzheimer's disease (AD) and related dementias given the prevalence of AD and the evolving neuroscience landscape in matters of diagnoses and therapeutics. Much of the ethics discussion arises in the tension between the principle of not doing harm (principle of non-maleficence) in this vulnerable population and the development of effective treatments (principle of beneficence). Autonomy and capacity issues are also numerous, wide-ranging, and concern (1) day to day affairs such as driving safely and spending money wisely, (2) life-time events such as designating a legal representative in case of incapacity, making a will, (3) consenting to treatment and diagnostic procedures, (4) participating in research. The latter issue is particularly thorny and illustrates well the complexity of tackling concerns related to capacity. The impetus to protect AD patients has partly led to ethics regulation and policies making research on inapt patients more difficult because of stringent requirements for signed informed consent or for showing the value of the research to this specific patient population. New issues are arising that relate to earlier diagnosis using biomarkers and (possibly soon) the use of drugs that modify disease progression. We here summarize and discuss the different ethical issues associated with AD from a historical perspective, with emphasis on diagnostic and treatments issues.

Consensus recommendations for the use of anti-egfr therapies in metastatic colorectal cancer.

In January 2010, a panel of Canadian oncologists with particular expertise in colorectal cancer (crc) gathered to develop a consensus guideline on the use of therapies against the epidermal growth factor receptor (egfr) in the management of metastatic crc (mcrc). This paper uses a case-based approach to summarize the consensus recommendations developed during that meeting.These are the consensus recommendations:Testing for the KRAS status of the tumour should be performed as soon as an egfr inhibitor is being considered as an option for treatment.Anti-egfr therapies are not recommended for the treatment of patients with tumours showing mutated KRAS status.For a patient with wild-type KRAS and an Eastern Cooperative Oncology Group status of 0-2, whose mcrc has previously been treated with a fluoropyrimidine, irinotecan, and oxaliplatin, switching to an egfr inhibitor is a recommended strategy.Cetuximab, cetuximab plus irinotecan, and panitumumab are all options for third-line therapy in patients with wild-type KRAS, provided that tolerability is acceptable.