PRESTO 2: An International Survey to Evaluate Patients' Injection Experiences with the Latest Devices/Formulations of Long-Acting Somatostatin Analog Therapies for Neuroendocrine Tumors or Acromegaly.

INTRODUCTION: Real-world data evaluating patients' injection experiences using the latest devices/formulations of the long-acting (LA) somatostatin analogs (SSAs) lanreotide Autogel/Depot (LAN; Somatuline®) and octreotide LA release (OCT; Sandostatin®) are limited. METHODS: PRESTO 2 was a 2020/2021 e-survey comparing injection experience of adults with neuroendocrine tumors (NETs) or acromegaly treated with LAN prefilled syringe versus OCT syringe for > 3 months in Canada, Ireland, the UK and the USA (planned sample size, 304). PRIMARY ENDPOINT: the proportion of patients with injection-site pain lasting > 2 days after their most recent injection, analyzed using a multivariate logistic regression model. Secondary endpoints included interference with daily life due to injection-site pain and technical injection problems in patients with current SSA use for ≥ 6 months. RESULTS: There were 304 respondents (acromegaly, n = 85; NETs, n = 219; LAN, n = 168; OCT, n = 136; 69.2% female; mean age, 59.6 years). Fewer patients had injection-site pain lasting > 2 days after the most recent injection with LAN (6.0%) than OCT (22.8%); the odds of pain lasting > 2 days were significantly lower for LAN than OCT, adjusted for disease subgroup and occurrence of injection-site reactions (odds ratio [95% confidence interval]: 0.13 [0.06-0.30]; p < 0.0001). Injection-site pain interfered with daily life "a little bit" or "quite a bit" in 37.2% and 3.8% (LAN) versus 52.5% and 7.5% (OCT) of patients, respectively. Among patients with ≥ 6 months' experience with current SSA (92.4% of patients), technical injection problems never occurred in 76.8% (LAN) and 42.9% (OCT) of patients. CONCLUSIONS: Compared with OCT, significantly fewer patients using LAN had injection-site pain lasting > 2 days after their most recent injection. Also, fewer LAN-treated patients experienced technical problems during injection. These findings demonstrate the importance of injection modality for overall LA SSA injection experience for patients with acromegaly or NETs.

Patients with neuroendocrine tumors or acromegaly often receive long-term monthly treatment with somatostatin analogs. These injectable drugs stop the body from making an excess of certain hormones. Understanding patients' experiences of these injections helps to provide better care. The PRESTO 2 online study surveyed 304 patients in Canada, Ireland, the UK and the USA with neuroendocrine tumors or acromegaly who were being treated with a somatostatin analog, either lanreotide Autogel/Depot (LAN) or octreotide long-acting release (OCT). The survey asked about injection experience, including injection-site pain lasting > 2 days and how it affected patients' lives, anxiety before injections and technical problems during injections (like syringe blockages). The survey showed fewer patients receiving LAN than OCT had injection-site pain that lasted > 2 days, and fewer said that the pain interfered with their daily lives. There were fewer technical injection problems with LAN than with OCT. However, more patients receiving LAN than OCT felt anxious before their injection. In some countries (including Canada, Ireland and the UK, but not the USA), the patient (or family member/friend) can inject LAN if they are on a stable dose, their doctor agrees, and they received training. A nurse/doctor must inject OCT. In PRESTO 2, about 40% of non-US patients who were eligible injected themselves (or were helped by a family member/friend). This may explain why more patients reported anxiety in the LAN group. PRESTO 2 provides important insights into patients' experiences of receiving somatostatin analogs and helps identify areas for improving patient care.

Characterizing Hypertension Specialist Care in Canada: A National Survey.

Background: The hypertension specialist often receives referrals of patients with young-onset, severe, difficult-to-control hypertension, patients with hypertensive emergencies, and patients with secondary causes of hypertension. Specialist hypertension care compliments primary care for these complex patients and contributes to an overall hypertension control strategy. The objective of this study was to characterize hypertension centres and the practice patterns of Canadian hypertension specialists. Methods: Adult hypertension specialists across Canada were surveyed to describe hypertension centres and specialist practice in Canada, including the following: the patient population managed by hypertension specialists; details on how care is provided; practice pattern variations; and differences in access to specialized hypertension resources across the country. Results: The survey response rate was 73.5% from 25 hypertension centres. Most respondents were nephrologists and general internal medicine specialists. Hypertension centres saw between 50 and 2500 patients yearly. A mean of 17% (± 15%) of patients were referred from the emergency department and a mean of 52% (± 24%) were referred from primary care. Most centres had access to specialized testing (adrenal vein sampling, level 1 sleep studies, autonomic testing) and advanced therapies for resistant hypertension (renal denervation). Considerable heterogeneity was present in the target blood pressure in young people with low cardiovascular risk and in the diagnostic algorithms for investigating secondary causes of hypertension. Conclusions: These results summarize the current state of hypertension specialist care and highlight opportunities for further collaboration among hypertension specialists, including standardization of the approach to specialist care for patients with hypertension.

Contexte: Le spécialiste de l'hypertension reçoit souvent des patients orientés pour une hypertension sévère, d'apparition précoce et difficile à maîtriser, pour une urgence hypertensive ou pour des causes secondaires de l'hypertension. Les soins spécialisés de l'hypertension complètent les soins primaires pour ces cas complexes et font partie d'une stratégie globale de maîtrise de l'hypertension. Cette étude avait pour objectif de caractériser les centres de traitement de l'hypertension et les habitudes de pratique des spécialistes canadiens qui traitent l'hypertension. Méthodologie: Un sondage a été mené auprès de spécialistes de l'hypertension adulte de l'ensemble du Canada afin de décrire les centres de traitement de l'hypertension et la pratique des spécialistes au Canada, notamment les éléments suivants : la population de patients prise en charge par des spécialistes de l'hypertension, les renseignements sur la façon dont les soins sont prodigués, les variations dans les habitudes de pratique ainsi que les différences relatives à l'accès aux ressources spécialisées en hypertension à l'échelle du pays. Résultats: Le taux de réponse au sondage a été de 73,5 % dans 25 centres de l'hypertension. La plupart des répondants étaient des néphrologues et des spécialistes en médecine interne générale. Les centres de l'hypertension recevaient entre 50 et 2500 patients par année. En moyenne, 17 % (± 15 %) des patients provenaient du service des urgences et 52 % (± 24 %) provenaient d'une unité de soins primaires. La plupart des centres avaient accès à des tests spécialisés (prélèvements veineux surrénaliens, études du sommeil de niveau 1, tests autonomes) et à des traitements avancés pour l'hypertension résistante (dénervation rénale). Une hétérogénéité considérable a été constatée en ce qui concerne la pression artérielle cible chez les jeunes présentant un faible risque cardiovasculaire et les algorithmes diagnostiques pour étudier les causes secondaires de l'hypertension. Conclusions: Ces résultats résument la situation actuelle des soins spécialisés de l'hypertension et font ressortir des occasions d'accroître la collaboration entre les spécialistes de l'hypertension, notamment en ce qui concerne une normalisation de l'approche des soins spécialisés pour les patients hypertendus.

Hypertension Canada's 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

PREDICTIVE MARKERS FOR POSTSURGICAL MEDICAL MANAGEMENT OF ACROMEGALY: A SYSTEMATIC REVIEW AND CONSENSUS TREATMENT GUIDELINE.

Objective: To clarify the selection of medical therapy following transsphenoidal surgery in patients with acromegaly, based on growth hormone (GH)/insulin-like growth factor 1 (IGF-1) response and glucometabolic control. Methods: We carried out a systematic literature review on three of the best studied and most practical predictive markers of the response to somatostatin analogues (SSAs): somatostatin receptor (SSTR) expression, tumor morphologic classification, and T2-weighted magnetic resonance imaging (MRI) signal intensity. Additional analyses focused on glucose metabolism in treated patients. Results: The literature survey confirmed significant associations of all three factors with SSA responsiveness. SSTR expression appears necessary for the SSA response; however, it is not sufficient, as approximately half of SSTR2-positive tumors failed to respond clinically to first-generation SSAs. MRI findings (T2-hypo-intensity) and a densely granulated phenotype also correlate with SSA efficacy, and are advantageous as predictive markers relative to SSTR expression alone. Glucometabolic control declines with SSA monotherapy, whereas GH receptor antagonist (GHRA) monotherapy may restore normoglycemia. Conclusion: We propose a decision tree to guide selection among SSAs, dopamine agonists (DAs), and GHRA for medical treatment of acromegaly in the postsurgical setting. This decision tree employs three validated predictive markers and other clinical considerations, to determine whether SSAs are appropriate first-line medical therapy in the postsurgical setting. DA treatment is favored in patients with modest IGF-1 elevation. GHRA treatment should be considered for patients with T2-hyperintense tumors with a sparsely granulated phenotype and/or low SSTR2 staining, and may also be favored for individuals with diabetes. Prospective analyses are required to test the utility of this therapeutic paradigm. Abbreviations: DA = dopamine agonist; DG = densely granulated; GH = growth hormone; GHRA = growth hormone receptor antagonist; HbA1c = glycated hemoglobin; IGF-1 = insulin-like growth factor-1; MRI = magnetic resonance imaging; SG = sparsely granulated; SSA = somatostatin analogue; SSTR = somatostatin receptor.

Tools for Enhancement and Quality Improvement of Peer Assessment and Clinical Care in Endocrinology and Metabolism.

Members of the College of Physicians and Surgeons of Ontario Endocrinology and Metabolism Peer Review Network have been involved in a quality improvement project to help standardize the peer assessment of physicians practicing in endocrinology and metabolism. This has included developing state-of-the-art summaries of common endocrine problems by Canadian experts in endocrinology and metabolism. These tools have been developed in response to the educational needs, as identified by peer reviewers, of practicing endocrinologists in Ontario. These pedagogical tools aim not only to standardize the documentation of the clinical performance of endocrinologists but also to make the process more transparent and to improve the quality of patient care in Ontario. This article summarizes the project and also provides the tools developed for the endocrinology and metabolism section of the College of Physicians and Surgeons of Ontario.

Spontaneous heparin-induced thrombocytopenia syndrome presenting as bilateral adrenal infarction after knee arthroplasty.

Adrenal gland infarction resulting from adrenal vein thrombosis is an infrequently recognised entity with a limited differential diagnosis. When bilateral, it can result in acute life-threatening adrenal failure. Heparin-induced thrombocytopenia (HIT) is an antibody-mediated, prothrombotic state that represents an important cause of adrenal vein thrombosis leading to associated infarction. Sometimes, the clinical picture of HIT-including the presence of HIT antibodies-occurs despite absence of proximate heparin exposure ('spontaneous HIT syndrome'). We report a case of nearly missed adrenal failure secondary to bilateral adrenal infarction that evolved during the second week following knee arthroplasty (a known trigger of spontaneous HIT syndrome). The combination of bilateral adrenal infarction, thrombocytopenia and presence of platelet-activating HIT antibodies not explainable by preceding heparin exposure led to a diagnosis of postknee arthroplasty spontaneous HIT syndrome. The case also highlights the clinical and laboratory findings associated with rapidly progressive acute adrenal failure.

Hypertension Canada's 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines are introduced, and 1 existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke is revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guideline-directed heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed.

The Potential Role of Primary Care in Case Detection/Screening of Primary Aldosteronism.

Endocrine hypertension, particularly primary aldosteronism (PA), was previously considered to account for less than 1% of all hypertension and was suspected only when patients presented with spontaneous hypokalemia. However, the last 20 years of PA research has now clearly shown that PA is not a rarity, but rather, may account for up to 13% of unselected hypertensive individuals and between 10% and 20% of those with resistant hypertension. Most of these patients do not have spontaneous hypokalemia. The population prevalence of PA likely far exceeds actual detection rates in routine clinical care. As PA represents one of the most common, potentially reversible causes of hypertension, and is associated with significant cardiovascular complications over the long term, it is clear that a pragmatic strategy for targeted case detection in primary care is needed.

Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension.

Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure. Also, although a serum lipid panel remains part of the routine laboratory testing for patients with hypertension, fasting and nonfasting collections are now considered acceptable. For individuals with secondary hypertension arising from primary hyperaldosteronism, adrenal vein sampling is recommended for those who are candidates for potential adrenalectomy. With respect to the treatment of hypertension, a new recommendation that has been added is for increasing dietary potassium to reduce blood pressure in those who are not at high risk for hyperkalemia. Furthermore, in selected high-risk patients, intensive blood pressure reduction to a target systolic blood pressure ≤ 120 mm Hg should be considered to decrease the risk of cardiovascular events. Finally, in hypertensive individuals with uncomplicated, stable angina pectoris, either a ß-blocker or calcium channel blocker may be considered for initial therapy. The specific evidence and rationale underlying each of these recommendations are discussed. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will continue to provide annual updates.

The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended. A standardized ambulatory blood pressure monitoring protocol and an update on automated office blood pressure are also presented. Several other recommendations on accurate measurement of blood pressure and criteria for diagnosis of hypertension have been reorganized. Two other new recommendations refer to smoking cessation: (1) tobacco use status should be updated regularly and advice to quit smoking should be provided; and (2) advice in combination with pharmacotherapy for smoking cessation should be offered to all smokers. The following recommendations were modified: (1) renal artery stenosis should be primarily managed medically; and (2) renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled hypertension. The rationale for these recommendation changes is discussed.

The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

Herein, updated evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in Canadian adults are detailed. For 2014, 3 existing recommendations were modified and 2 new recommendations were added. The following recommendations were modified: (1) the recommended sodium intake threshold was changed from ≤ 1500 mg (3.75 g of salt) to approximately 2000 mg (5 g of salt) per day; (2) a pharmacotherapy treatment initiation systolic blood pressure threshold of ≥ 160 mm Hg was added in very elderly (age ≥ 80 years) patients who do not have diabetes or target organ damage (systolic blood pressure target in this population remains at < 150 mm Hg); and (3) the target population recommended to receive low-dose acetylsalicylic acid therapy for primary prevention was narrowed from all patients with controlled hypertension to only those ≥ 50 years of age. The 2 new recommendations are: (1) advice to be cautious when lowering systolic blood pressure to target levels in patients with established coronary artery disease if diastolic blood pressure is ≤ 60 mm Hg because of concerns that myocardial ischemia might be exacerbated; and (2) the addition of glycated hemoglobin (A1c) in the diagnostic work-up of patients with newly diagnosed hypertension. The rationale for these recommendation changes is discussed. In addition, emerging data on blood pressure targets in stroke patients are discussed; these data did not lead to recommendation changes at this time. The Canadian Hypertension Education Program recommendations will continue to be updated annually.

Desmoplastic small round cell tumour in a 74 year old man: an uncommon cause of ascites (case report).

A rare case is provided of a 74 year old man who presented with ascites of unknown etiology. CT scan of the abdomen revealed extensive omental caking, and omental biopsy cytogenetics showed findings in keeping with a diagnosis of desmoplastic small round cell tumour (DSRCT). This case is unique in that it involves a significantly older patient, negative WT1 immunohistochemical staining, and negative cytology. Despite repeated paracenteses and fluid management, the patient died in hospital secondary to renal complications.

A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma.

BACKGROUND: Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. METHODS: We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. RESULTS: Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%-100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%-100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07). CONCLUSION: Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma.