Cushing syndrome from an ACTH-producing pheochromocytoma or paraganglioma: structured review of 94 cases.

Adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas are rare neuroendocrine tumors that co-secrete excess catecholamines and adrenocorticotropic hormone, resulting in Cushing syndrome (CS). This review aims to summarize important patient characteristics, investigations, and outcomes in all cases reported in the English literature. A literature search was conducted to identify all English-language case reports and case series describing adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas. Relevant characteristics were systematically recorded. Cases that did not provide definitive evidence of an adrenocorticotropin (ACTH)-producing pheochromocytoma/paraganglioma were excluded. Our search strategy identified 93 published cases that met the inclusion criteria. We additionally reported one patient for a total of 94 cases. Details related to patient characteristics, laboratory data, and outcomes were commonly underreported. The median age was 47 years, and females accounted for 72% of cases. A cushingoid appearance was reported in 82% of patients, and hypertension in 86%. Infections were reported in 23% of patients. Urinary metanephrines were elevated at least three-fold above normal in 74% of cases. ACTH levels were high in 88% of patients and inappropriately normal in 12%. The median 24-hour urinary cortisol was 21-fold the upper limit of normal. Adrenalectomy was performed in nearly all patients, with 88% achieving a cure for both catecholamine and glucocorticoid excess. A total of 11 patients died. Metastases were uncommon (6%). Adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas are associated with considerable morbidity and mortality. It should be considered in the diagnostic workup of all patients with ectopic CS. Surgical cure is achieved in most patients, and infections are the leading cause of peri-operative mortality.

Sex-Specific Associations of Aldosterone and Renin with Body Composition: A Population-Based Cohort Study.

CONTEXT: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood. OBJECTIVE: To investigate the associations of aldosterone and renin with body composition according to sex in the general population. DESIGN: Population-based cohort study. SETTING: Québec (Canada). PARTICIPANTS: Adults aged 40-69 years enrolled to CARTaGENE between 2009 and 2010 (N=3,687). EXPOSURES: Plasma aldosterone and renin concentrations. MAIN OUTCOME MEASURES: Body composition assessed via anthropometrics (waist circumference and waist-to-hip ratio), bioelectrical impedance (lean body mass, fat mass, and muscle mass), and cardiac magnetic resonance imaging (epicardial and pericardial adipose tissue volumes). RESULTS: The mean (SD) age and body mass index were 55 (8) years and 27.3 (4.8) kg/m2, respectively. Among males, higher aldosterone and renin were associated with increased waist circumference, increased waist-to-hip ratio, increased fat mass, decreased lean body mass, and decreased muscle mass (p<0.05). Aldosterone (p=0.02), but not renin (p=0.43), was associated with increased ectopic cardiac adiposity in males. In contrast, higher renin (p<0.05), but not aldosterone (p≥0.05), was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity in females. Among females, higher renin and aldosterone were associated with increased fat mass (p<0.05) but were not associated with lean body mass or muscle mass (p≥0.05). All aforementioned associations were independent of body weight. CONCLUSIONS: Independent of body weight, increased RAAS activity is associated with unfavorable differences in body composition; however, the strength and pattern of association varies by sex.

Measurements of Postmenopausal Serum Estradiol Levels and Cardiovascular Events: A Systematic Review.

Background: Cardiovascular disease (CVD) is the leading cause of death among female patients and its likelihood increases following menopause. However, whether estradiol levels are related to CVD remains unknown. We aimed to determine the association between serum estradiol levels and cardiovascular (CV) events in postmenopausal females. Methods: Electronic databases (MEDLINE, Embase) were searched systematically from inception to October 2022. Studies were eligible for inclusion if they included the following: (i) postmenopausal females; (ii) examination of the association between total serum estradiol levels and CV events (CV mortality, CVD, coronary heart disease, myocardial infarction, stroke, venous thromboembolism, heart failure, and CV hospitalization); (iii) original data (randomized controlled trial, quasi-experimental, cohort, case-control, or cross-sectional study). A narrative synthesis was completed because the data were not amenable to meta-analysis. Results: Of the 9026 citations retrieved, 8 articles were included, representing a total of 5635 women. The risk-of-bias was fair, and considerable heterogeneity was present. In those not using menopausal hormone therapy, 3 studies demonstrated mixed results between estradiol levels and risk of coronary heart disease, and 1 study showed that higher estradiol levels were associated with an increased risk of myocardial infarction. No significant associations were present between estradiol levels and the remaining events (ie, CV mortality, heart failure, CVD, and stroke). Conclusions: The association between serum estradiol levels and CV events in postmenopausal females remains unclear. Further studies assessing this association are warranted, given the elevated CVD risk in this population.

Contexte: Les maladies cardiovasculaires (MCV) sont la principale cause de décès chez les femmes et leur probabilité augmente après la ménopause. Cependant, on ne sait pas encore si le taux d'estradiol est lié aux MCV. Nous avons tenté d'établir le lien entre le taux d'estradiol sérique et les événements cardiovasculaires (CV) chez les femmes post-ménopausées. Méthodologie: Nous avons consulté systématiquement des bases de données électroniques (MEDLINE, Embase) de leur création jusqu'en octobre 2022. Les études admissibles devaient comprendre les éléments suivants : i) femmes post-ménopausées; ii) examen du lien entre le taux total d'estradiol sérique et les événements CV (décès d'origine CV, MCV, coronaropathie, infarctus du myocarde, accident vasculaire cérébral (AVC), thromboembolie veineuse, insuffisance cardiaque et hospitalisation pour une cause CV); iii) données originales (essai contrôlé randomisé; études quasi expérimentales, de cohorte, cas-témoins ou transversales). Une synthèse narrative a été réalisée parce que les données ne se prêtaient pas à une méta-analyse. Résultats: Parmi les 9 026 citations relevées, 8 articles ont été retenus, représentant un total de 5 635 femmes. Le risque de biais était raisonnable, et une très grande hétérogénéité était présente. Chez les femmes qui ne suivaient pas d'hormonothérapie ménopausique, trois études ont affiché des résultats variables quant au lien entre le taux d'estradiol et le risque de coronaropathie, et une étude a montré que des taux élevés d'estradiol étaient associés à un risque accru d'infarctus du myocarde. Aucun lien notable n'a été observé entre le taux d'estradiol et les autres événements (c.-à-d. décès d'origine CV, insuffisance cardiaque, MCV et AVC). Conclusions: Le lien entre le taux d'estradiol sérique et les événements CV chez les femmes post-ménopausées n'a pas été élucidé. D'autres études sont nécessaires pour évaluer ce lien en raison du risque élevé de MCV au sein de cette population.

Biomarkers to Guide Medical Therapy in Primary Aldosteronism.

Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed.

Time to Benefit of Surgery vs Targeted Medical Therapy for Patients With Primary Aldosteronism: A Meta-analysis.

CONTEXT: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, but the comparative outcomes of targeted treatment remain unclear. OBJECTIVE: To compare the clinical outcomes in patients treated for primary aldosteronism over time. METHODS: Medline and EMBASE were searched. Original studies reporting the incidence of mortality, major adverse cardiovascular outcomes (MACE), progression to chronic kidney disease, or diabetes following adrenalectomy vs medical therapy were selected. Two reviewers independently abstracted data and assessed study quality. Standard meta-analyses were conducted using random-effects models to estimate relative differences. Time to benefit meta-analyses were conducted by fitting Weibull survival curves to estimate absolute risk differences and pooled using random-effects models. RESULTS: 15 541 patients (16 studies) with PA were included. Surgery was consistently associated with an overall lower risk of death (hazard ratio [HR] 0.34, 95% CI 0.22-0.54) and MACE (HR 0.55, 95% CI 0.36-0.84) compared with medical therapy. Surgery was associated with a significantly lower risk of hospitalization for heart failure (HR 0.48 95% CI 0.34-0.70) and progression to chronic kidney disease (HR 0.62 95% CI 0.39-0.98), and nonsignificant reductions in myocardial infarction and stroke. In absolute terms, 200 patients would need to be treated with surgery instead of medical therapy to prevent 1 death after 12.3 (95% CI 3.1-48.7) months. CONCLUSION: Surgery is associated with lower all-cause mortality and MACE than medical therapy for PA. For most patients, the long-term surgical benefits outweigh the short-term perioperative risks.

Multiple radiologist review of adrenal CT still frequently misses lateralized surgical primary aldosteronism.

Patients with primary aldosteronism (PA) have increased morbidity and mortality compared to those with essential hypertension. Accurate detection of lateralized PA is important so that affected patients can receive potentially curative adrenalectomy. However, around 40% of patients with lateralized PA have "normal" adrenal glands on computed tomography (CT). Additional independent review of imaging has been shown to improve diagnostic accuracy in many areas of imaging. Therefore, the authors sought to establish if multi-reader re-assessment of previously reported normal CT scans would result in increased detection of surgically remediable disease. The authors found that re-assessment of CT imaging by one, two, or three additional radiologists (or a combination thereof) slightly increased the detection of lateralized disease, but these differences were not statistically significant (p > .05). Readers had low inter-observer agreement (kappa = 0.17). If detection of a discrete nodule on CT was made a prerequisite for adrenal vein sampling (AVS), a second read by another reviewer would still result in an excess of missed cases (84.2%, 36.8%, and 65.8%, respectively, for each of the three independent reviewers). Therefore, a "normal" CT does not preclude the possibility of lateralized PA. Adrenal vein sampling should still be strongly considered wherever available and whenever surgery is considered for treatment of PA, irrespective of CT findings.

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Use of Epic Electronic Health Record System for Health Care Research: Scoping Review.

BACKGROUND: Electronic health records (EHRs) enable health data exchange across interconnected systems from varied settings. Epic is among the 5 leading EHR providers and is the most adopted EHR system across the globe. Despite its global reach, there is a gap in the literature detailing how EHR systems such as Epic have been used for health care research. OBJECTIVE: The objective of this scoping review is to synthesize the available literature on use cases of the Epic EHR for research in various areas of clinical and health sciences. METHODS: We used established scoping review methods and searched 9 major information repositories, including databases and gray literature sources. To categorize the research data, we developed detailed criteria for 5 major research domains to present the results. RESULTS: We present a comprehensive picture of the method types in 5 research domains. A total of 4669 articles were screened by 2 independent reviewers at each stage, while 206 articles were abstracted. Most studies were from the United States, with a sharp increase in volume from the year 2015 onwards. Most articles focused on clinical care, health services research and clinical decision support. Among research designs, most studies used longitudinal designs, followed by interventional studies implemented at single sites in adult populations. Important facilitators and barriers to the use of Epic and EHRs in general were identified. Important lessons to the use of Epic and other EHRs for research purposes were also synthesized. CONCLUSIONS: The Epic EHR provides a wide variety of functions that are helpful toward research in several domains, including clinical and population health, quality improvement, and the development of clinical decision support tools. As Epic is reported to be the most globally adopted EHR, researchers can take advantage of its various system features, including pooled data, integration of modules and developing decision support tools. Such research opportunities afforded by the system can contribute to improving quality of care, building health system efficiencies, and conducting population-level studies. Although this review is limited to the Epic EHR system, the larger lessons are generalizable to other EHRs.

Revising the Roles of Aldosterone in Vascular Physiology and Pathophysiology: From Electocortin to Baxdrostat.

Aldosterone was initially identified as a hormone primarily related to regulation of fluid and electrolyte homeostasis. However, over the past 20 years there has been an increasing appreciation of its role in regulation of vascular function and pathophysiology in the setting of hypertension, atherosclerosis, and heart failure. This review highlights recent advances in our understanding the biology of aldosterone as it relates to the pathophysiology and the management of vascular disease-especially related to hypertension. The review focuses on 3 key areas: 1) advances in our understanding of the cellular mechanisms by which aldosterone mediates its cellular effects, 2) identification of the hidden epidemic of aldosteronism as a mediator of hypertension, and 3) appreciating new therapeutic advances in the clinical pharmacology of aldosterone inhibition in cardiovascular and renal disease.

Small for gestational age preterm infants and later adiposity and height: A systematic review and meta-analysis.

BACKGROUND: Overweight and obesity and their consequent morbidities are important worldwide health problems. Some research suggests excess adiposity origins may begin in fetal life, but unknown is whether this applies to infants born preterm. OBJECTIVE: The objective of the study was to assess the association between small for gestational age (SGA) birth and later adiposity and height among those born preterm. DATA SOURCES: MEDLINE, EMBASE and CINAHL until October 2022. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they reported anthropometric (adiposity measures and height) outcomes for participants born preterm with SGA versus non-SGA. Screening, data extraction and risks of bias assessments were conducted in duplicate by two reviewers. SYNTHESIS: We meta-analysed across studies using random-effects models and explored potential heterogeneity sources. RESULTS: Thirty-nine studies met the inclusion criteria. In later life, preterm SGA infants had a lower body mass index (-0.66 kg/m2 , 95% CI -0.79, -0.53; 32 studies, I2 = 16.7, n = 30,346), waist circumference (-1.20 cm, 95% CI -2.17, -0.23; 13 studies, I2 = 19.4, n = 2061), lean mass (-2.62 kg, 95% CI -3.45, 1.80; 7 studies, I2 = 0, n = 205) and height (-3.85 cm, 95% CI -4.73, -2.96; 26 studies, I2 = 52.6, n = 4174) compared with those preterm infants born non-SGA. There were no differences between preterm SGA and preterm non-SGA groups in waist/hip ratio, body fat, body fat per cent, truncal fat per cent, fat mass index or lean mass index, although power was limited for some analyses. Studies were rated at high risk of bias due to potential residual confounding and low risk of bias in other domains. CONCLUSIONS: Compared to their preterm non-SGA peers, preterm infants born SGA have lower BMI, waist circumference, lean body mass and height in later life. No differences in adiposity were observed between SGA preterm infants and non-SGA preterm infants.

20-year trends in multimorbidity by race/ethnicity among hospitalized patient populations in the United States.

BACKGROUND: The challenges presented by multimorbidity continue to rise in the United States. Little is known about how the relative contribution of individual chronic conditions to multimorbidity has changed over time, and how this varies by race/ethnicity. The objective of this study was to describe trends in multimorbidity by race/ethnicity, as well as to determine the differential contribution of individual chronic conditions to multimorbidity in hospitalized populations over a 20-year period within the United States. METHODS: This is a serial cross-sectional study using the Nationwide Inpatient Sample (NIS) from 1993 to 2012. We identified all hospitalized patients aged ≥ 18 years old with available data on race/ethnicity. Multimorbidity was defined as the presence of 3 or more conditions based on the Elixhauser comorbidity index. The relative change in the proportion of hospitalized patients with multimorbidity, overall and by race/ethnicity (Black, White, Hispanic, Asian/Pacific Islander, Native American) were tabulated and presented graphically. Population attributable fractions were estimated from modified Poisson regression models adjusted for sex, age, and insurance type. These fractions were used to describe the relative contribution of individual chronic conditions to multimorbidity over time and across racial/ethnic groups. RESULTS: There were 123,613,970 hospitalizations captured within the NIS between 1993 and 2012. The prevalence of multimorbidity increased in all race/ethnic groups over the 20-year period, most notably among White, Black, and Native American populations (+ 29.4%, + 29.7%, and + 32.0%, respectively). In both 1993 and 2012, Black hospitalized patients had a higher prevalence of multimorbidity (25.1% and 54.8%, respectively) compared to all other race/ethnic groups. Native American populations exhibited the largest overall increase in multimorbidity (+ 32.0%). Furthermore, the contribution of metabolic diseases to multimorbidity increased, particularly among Hispanic patients who had the highest population attributable fraction values for diabetes without complications (15.0%), diabetes with complications (5.1%), and obesity (5.8%). CONCLUSIONS: From 1993 to 2012, the secular increases in the prevalence of multimorbidity as well as changes in the differential contribution of individual chronic conditions has varied substantially by race/ethnicity. These findings further elucidate the racial/ethnic gaps prevalent in multimorbidity within the United States. PRIOR PRESENTATIONS: Preliminary finding of this study were presented at the Society of General Internal Medicine (SGIM) Annual Conference, Washington, DC, April 21, 2017.

The impact of updated clinical blood pressure guidelines on hypertension prevalence among children and adolescents.

Background: To date, population estimates of hypertension prevalence among children and adolescents in Canada have been based on clinical guidelines in the National High Blood Pressure Education Program's 2004 Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (NHBPEP 2004). In 2017, the American Academy of Pediatrics published updated guidelines in Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents (AAP 2017), followed by Hypertension Canada in 2020 with its publication of Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children (HC 2020). This study compares national child and adolescent hypertension prevalence estimates based on NHBPEP 2004, AAP 2017 and HC 2020. Data and methods: Six cycles of data spanning 2007 to 2019 from the Canadian Health Measures Survey were used to compare blood pressure (BP) categories and the prevalence of hypertension by sex and age group under all sets of guidelines for children and adolescents aged 6 to 17. The impact of applying AAP 2017 across time and selected characteristics, the resulting reclassification into a higher BP category under AAP 2017, and differences in hypertension prevalence resulting from applying HC 2020 versus AAP 2017 were examined. Results: Prevalence of Stage 1 hypertension was higher among children and adolescents aged 6 to 17 under AAP 2017 and HC 2020 than under NHBPEP 2004. Overall hypertension prevalence was also higher, and obesity was a major factor associated with being reclassified into a higher BP category under AAP 2017. Interpretation: Implementation of AAP 2017 and HC 2020 is associated with significant changes in the epidemiology of hypertension. Understanding the impact of applying updated clinical guidelines may help inform population surveillance efforts to track hypertension prevalence among Canada's children and adolescents.

Screening for Primary Aldosteronism Among Hypertensive Adults with Obstructive Sleep Apnea: A Retrospective Population-Based Study.

BACKGROUND: Hypertension plus obstructive sleep apnea (OSA) is recommended in some guidelines as an indication to screen for primary aldosteronism (PA), yet prior data has brought the validity of this recommendation into question. Given this context, it remains unknown whether this screening recommendation is being implemented into clinical practice. METHODS: We conducted a population-based retrospective cohort study of all adult Ontario (Canada) residents with hypertension plus OSA from 2009 to 2020 with follow-up through 2021 utilizing provincial health administrative data. We measured the proportion of individuals who underwent PA screening via the aldosterone-to-renin ratio by year. We further examined screening rates among patients with hypertension plus OSA by the presence of concurrent hypokalemia and resistant hypertension. Clinical predictors associated with screening were assessed via Cox regression modeling. RESULTS: The study cohort included 53,130 adults with both hypertension and OSA, of which only 634 (1.2%) underwent PA screening. Among patients with hypertension, OSA, and hypokalemia, the proportion of eligible patients screened increased to 2.8%. Among patients ≥65 years with hypertension, OSA, and prescription of ≥4 antihypertensive medications, the proportion of eligible patients screened was 1.8%. Older age was associated with a decreased likelihood of screening while hypokalemia and subspecialty care with internal medicine, cardiology, endocrinology, or nephrology were associated with an increased likelihood of screening. No associations with screening were identified with sex, rural residence, cardiovascular disease, diabetes, or respirology subspecialty care. CONCLUSIONS: The population-level uptake of the guideline recommendation to screen all patients with hypertension plus OSA for PA is exceedingly low.

Small for date preterm infants and risk of higher blood pressure in later life: A systematic review and meta-analysis.

BACKGROUND: Historical reports suggest that infants born small for gestational age (SGA) are at increased risk for high blood pressure (BP) at older ages after adjustment for later age body size. Such adjustment may be inappropriate since adiposity is a known cause of cardiovascular and metabolic disease. OBJECTIVES: To assess the association between SGA births and later BP among preterm births, considering potential background confounders and over-adjustment for later body size. METHODS: A database search of studies up to October 2022 included MEDLINE, EMBASE and CINAHL. Studies were included if they reported BP (systolic [SBP] or diastolic [DBP]) (outcomes) for participants born preterm with SGA (exposure) or non-SGA births. All screening, extraction steps, and risk of bias (using the Risk of Bias In Non-randomised Studies of Interventions [ROBINS-I] tool) were conducted in duplicate by two reviewers. Data were pooled in meta-analysis using random-effects models. We explored potential sources of heterogeneity. RESULTS: We found no meaningful difference in later BP between preterm infants with and without SGA status at birth. Meta-analysis of 25 studies showed that preterm SGA, compared to preterm non-SGA, was not associated with higher BP at age 2 and older with mean differences for SBP 0.01 mmHg (95% CI -0.10, 0.12, I2  = 59.8%, n = 20,462) and DBP 0.01 mm Hg (95% CI -0.10, 0.12), 22 studies, (I2  = 53.0%, n = 20,182). Adjustment for current weight did not alter the results, which could be due to the lack of differences in later weight status in most of the included studies. The included studies were rated to be at risk of bias due to potential residual confounding, with a low risk of bias in other domains. CONCLUSIONS: Evidence indicates that preterm infants born SGA are not at increased risk of developing higher BP as children or as adults as compared to non-SGA preterm infants.

A comparison of machine learning algorithms and traditional regression-based statistical modeling for predicting hypertension incidence in a Canadian population.

Risk prediction models are frequently used to identify individuals at risk of developing hypertension. This study evaluates different machine learning algorithms and compares their predictive performance with the conventional Cox proportional hazards (PH) model to predict hypertension incidence using survival data. This study analyzed 18,322 participants on 24 candidate features from the large Alberta's Tomorrow Project (ATP) to develop different prediction models. To select the top features, we applied five feature selection methods, including two filter-based: a univariate Cox p-value and C-index; two embedded-based: random survival forest and least absolute shrinkage and selection operator (Lasso); and one constraint-based: the statistically equivalent signature (SES). Five machine learning algorithms were developed to predict hypertension incidence: penalized regression Ridge, Lasso, Elastic Net (EN), random survival forest (RSF), and gradient boosting (GB), along with the conventional Cox PH model. The predictive performance of the models was assessed using C-index. The performance of machine learning algorithms was observed, similar to the conventional Cox PH model. Average C-indexes were 0.78, 0.78, 0.78, 0.76, 0.76, and 0.77 for Ridge, Lasso, EN, RSF, GB and Cox PH, respectively. Important features associated with each model were also presented. Our study findings demonstrate little predictive performance difference between machine learning algorithms and the conventional Cox PH regression model in predicting hypertension incidence. In a moderate dataset with a reasonable number of features, conventional regression-based models perform similar to machine learning algorithms with good predictive accuracy.

Selective treatment of nonsevere clinical mastitis does not adversely affect cure, somatic cell count, milk yield, recurrence, or culling: A systematic review and meta-analysis.

Treatment of clinical mastitis (CM) contributes to antimicrobial use on dairy farms. Selective treatment of CM based on bacterial diagnosis can reduce antimicrobial use, as not all cases of CM will benefit from antimicrobial treatment, e.g., mild and moderate gram-negative infections. However, impacts of selective CM treatment on udder health and culling are not fully understood. A systematic search identified 13 studies that compared selective versus blanket CM treatment protocols. Reported outcomes were synthesized with random-effects models and presented as risk ratios or mean differences. Selective CM treatment protocol was not inferior to blanket CM treatment protocol for the outcome bacteriological cure. Noninferiority margins could not be established for the outcomes clinical cure, new intramammary infection, somatic cell count, milk yield, recurrence, or culling. However, no differences were detected between selective and blanket CM treatment protocols using traditional analyses, apart from a not clinically relevant increase in interval from treatment to clinical cure (0.4 d) in the selective group and higher proportion of clinical cure at 14 d in the selective group. The latter occurred in studies co-administering nonsteroidal anti-inflammatories only in the selective group. Bias could not be ruled out in most studies due to suboptimal randomization, although this would likely only affect subjective outcomes such as clinical cure. Hence, findings were supported by a high or moderate certainty of evidence for all outcome measures except clinical cure. In conclusion, this review supported the assertion that a selective CM treatment protocol can be adopted without adversely influencing bacteriological and clinical cure, somatic cell count, milk yield, and incidence of recurrence or culling.

The impact of surgeon operative volume on risk of reoperation within 5 years of mid-urethral sling: a systematic review.

INTRODUCTION AND HYPOTHESIS: Undesired outcomes after mid-urethral sling (MUS), such as mesh exposure or surgical failure, can necessitate further procedures. The objective of this review is to evaluate the association between surgeon operative volume and the risk of reoperation after MUS. METHODS: Eligible studies were selected through an electronic literature search from database and references of the studies included. Databases were searched for original studies reporting on the MUS procedure, reoperation, and operative volume. Random effects models were used to estimate the pooled OR of reoperation according to surgeon volume. Outcomes were divided into two categories: mesh removal and/or revision and subsequent surgery for treatment of SUI. RESULTS: A total of 2,304 abstracts were screened, and 51 studies were assessed through full-text reading. Seven studies were included in the systematic review. High-volume and low-volume surgeons were defined differently in various studies. The odds ratio of the mesh removal/revision procedure was 1.26 (95%CI 1.03-1.53) among those who received their surgery from a low-volume surgeon compared with those who received their surgery from a high-volume surgeon as defined by the studies. The odds ratio of repeated incontinence procedures was 1.18 (95% CI 1.01-1.37). CONCLUSIONS: The odds of a repeat incontinence procedure appear higher if the surgery is performed by a low-volume surgeon, although these results need to be interpreted with caution as the definition of low-volume vs high-volume surgeon varied between studies. As such, operative volume should be included in surgical reporting, and future research should utilize surgical volume as either a continuous exposure or a standardized value of low- vs high-volume MUS surgeons.

Detecting Anxiety in Long-Term Care Residents: A Systematic Review.

Anxiety is common in long-term care (LTC), but it is unclear which anxiety detection tools are accurate when compared to a reference standard for residents of LTC. Four databases and grey literature sources were searched using the search concepts "anxiety" and "LTC". Included studies evaluated the diagnostic accuracy of an anxiety detection tool compared to a reference standard in LTC residents. Diagnostic accuracy measures were extracted. Four articles out of 4,620 met the inclusion criteria. Despite limited evidence and poorly reported study procedures and characteristics, the Geriatric Anxiety Inventory (sensitivity: 90.0%, specificity: 86.2%) and the Hospital Anxiety and Depression Scale-Anxiety (sensitivity: 90.0%, specificity: 80.6%) had the best performance when detecting generalized anxiety disorder. We identified four anxiety detection tools appropriate for use in LTC; a critical first step to diagnosing and managing anxiety in residents of LTC. Non-generalized anxiety disorders and tool feasibility must be further evaluated.

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.

Personalized prediction of incident hospitalization for cardiovascular disease in patients with hypertension using machine learning.

BACKGROUND: Prognostic information for patients with hypertension is largely based on population averages. The purpose of this study was to compare the performance of four machine learning approaches for personalized prediction of incident hospitalization for cardiovascular disease among newly diagnosed hypertensive patients. METHODS: Using province-wide linked administrative health data in Alberta, we analyzed a cohort of 259,873 newly-diagnosed hypertensive patients from 2009 to 2015 who collectively had 11,863 incident hospitalizations for heart failure, myocardial infarction, and stroke. Linear multi-task logistic regression, neural multi-task logistic regression, random survival forest and Cox proportional hazard models were used to determine the number of event-free survivors at each time-point and to construct individual event-free survival probability curves. The predictive performance was evaluated by root mean squared error, mean absolute error, concordance index, and the Brier score. RESULTS: The random survival forest model has the lowest root mean squared error value at 33.94 and lowest mean absolute error value at 28.37. Machine learning methods provide similar discrimination and calibration in the personalized survival prediction of hospitalizations for cardiovascular events in patients with hypertension. Neural multi-task logistic regression model has the highest concordance index at 0.8149 and lowest Brier score at 0.0242 for the personalized survival prediction. CONCLUSIONS: This is the first personalized survival prediction for cardiovascular diseases among hypertensive patients using administrative data. The four models tested in this analysis exhibited a similar discrimination and calibration ability in predicting personalized survival prediction of hypertension patients.