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Background Nursing home (NH) residents have been dramatically affected by COVID-19, with extremely high rates of hospitalization and mortality. Aims To describe the features and impact of an assistance model involving an intermediate care mobile medical specialist team (GIROT, Gruppo Intervento Rapido Ospedale Territorio) aimed at delivering “hospital-at-nursing home” care to NH residents with COVID-19 in Florence, Italy. Methods The GIROT activity was set-up during the first wave of the pandemic (W1, March–April 2020) and became a structured healthcare model during the second (W2, October 2020–January 2021). The activity involved (1) infection transmission control among NHs residents and staff, (2) comprehensive geriatric assessment including prognostication and geriatric syndromes management, (3) on-site diagnostic assessment and protocol-based treatment of COVID-19, (4) supply of nursing personnel to understaffed NHs. To estimate the impact of the GIROT intervention, we reported hospitalization and infection lethality rates recorded in SARS-CoV-2-positive NH residents during W1 and W2. Results The GIROT activity involved 21 NHs (1159 residents) and 43 NHs (2448 residents) during W1 and W2, respectively. The percentage of infected residents was higher in W2 than in W1 (64.5% vs. 38.8%), while both hospitalization and lethality rates significantly decreased in W2 compared to W1 (10.1% vs 58.2% and 23.4% vs 31.1%, respectively). Discussion Potentiating on-site care in the NHs paralleled a decrease of hospital admissions with no increase of lethality. Conclusions An innovative “hospital-at-nursing home” patient-centred care model based on comprehensive geriatric assessment may provide a valuable contribution in fighting COVID-19 in NH residents.

Over recent years, managing hypertension in older people has gained increasing attention, with reference to very old, frailer individuals. In these patients, hypertension treatment may be challenging due to a higher risk of hypotension-related adverse events which commonly overlaps with a higher cardiovascular risk. Additionally, frailer older adults rarely satisfy inclusion criteria of randomized clinical trials, which determines a substantial lack of scientific data. Although limited, available evidence suggests that the association between blood pressure and adverse outcomes significantly varies at advanced age according to frailty status. In particular, the negative prognostic impact of hypertension seems to attenuate or even revert in individuals with older biological age, e.g., patients with disability, cognitive impairment, and poor physical performance. Consequently, "one size does not fit all" and personalized treatment strategies are needed, customized to individuals' frailty and functional status. Similar to other cardiovascular diseases, hypertension management in older people should be characterized by a geriatric approach based on biological rather than chronological age and a geriatric comprehensive evaluation including frailty assessment is required to provide the most appropriate treatment, tailored to patients' prognosis and health care goals. The aim of this review was to illustrate the importance of a patient-centered geriatric approach to hypertension management in older people with the final purpose to promote a wider implementation of frailty assessment in routine practice.

Muscle mass is frequently reduced in older patients experiencing injurious falls and may further reduce during hospitalization for bone fracture. In these patients, renal function may be overestimated, because it is usually calculated using serum creatinine, which is strictly related to muscle mass. We evaluated if creatinine levels change during hospitalization in older patients with fracture. We also assessed the role of cystatin C as a more appropriate marker of renal function, comparing estimated glomerular filtration rate (eGFR) according to different formulas based on creatinine and/or cystatin C levels.Patients aged 65+ years, consecutively hospitalized for fracture, were enrolled in a prospective cohort study. Creatinine and cystatin C levels were measured at baseline and in the post-operative period; eGFR was calculated using six equations based on creatinine and/or cystatin C.425 patients were enrolled (mean age 84 years, mean creatinine 0.97 mg/dL, mean cystatin C 1.53 mg/L). Creatinine levels significantly decreased after surgery (p0.001), while cystatin C remained stable. According to creatinine-based formulas, eGFR was60 mL/min/1.73 mIn older fractured patients, creatinine levels decline during hospital stay and may possibly overestimate renal function, whereas cystatin C remains stable. Whether cystatin C is a more reliable marker of renal function in this specific population should be further investigated.

Background We hypothesized that cardiovascular physiology differs in reflex syncope patients compared with the general population, predisposing such individuals to vasovagal reflex. Methods In this multicohort cross-sectional study, we compared aggregate data of resting SBP, DBP, pulse pressure (PP) and heart rate (HR), collected from six community-based cohort studies (64 968 observations) with those from six databases of reflex syncope patients (6516 observations), subdivided by age decades and sex. Results Overall, in male individuals with reflex syncope, SBP (-3.4 mmHg) and PP (-9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages above 60 years. In female individuals, PP (-6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with male individuals, SBP in female individuals exhibited slower increase until age 40 years, and then demonstrated steeper increase that continued throughout remaining life. Conclusion The patients prone to reflex syncope demonstrate a different resting cardiovascular haemodynamic profile as compared with a general population, characterized by lower SBP and PP, reflecting reduced venous return and lower stroke volume, and a higher HR and DBP, suggesting the activation of compensatory mechanisms. Our data contribute to a better understanding why some individuals with similar demographic characteristics develop reflex syncope and others do not. Video abstract http://links.lww.com/HJH/B580.

Hypertension and hypotension are strictly related phenomena, that frequently coexist within the spectrum of cardiovascular autonomic dysfunction, especially at advanced age. Indeed, antihypertensive treatment may predispose to orthostatic and postprandial hypotension, while intensive blood pressure lowering may be responsible for systemic hypotension. Over recent years, systemic and orthostatic hypotension have emerged as important although often neglected risk factors for adverse outcomes, paralleling the widely recognized arterial hypertension. Both hypertension and hypotension are associated with detrimental effects on target organs and survival, thus significantly impacting patients' prognosis, functional autonomy, and Quality of Life. Balancing low and high blood pressure requires accurate diagnostic assessment of blood pressure values and patients' hypotensive susceptibility, which allow for the development of customized treatment strategies based on individual hypo/hypertensive risk profile. The present review illustrates the complex interrelationship between hypotension and hypertension and discusses the relevant prognostic role of these conditions. Additionally, it provides an overview on hypotension detection and treatment in patients with hypertension, focusing on customized diagnostic and therapeutic strategies.

Hypertension management is challenging in frail older adults. The balance between treatment risks and benefits may be difficult to achieve due to an increased vulnerability to treatment-related adverse events, and limited evidence is available to support clinical decisions. The effects of frailty on blood pressure are unclear, as well as its impact on antihypertensive treatment benefits. Appropriate blood pressure targets in frail patients are debated and the frailty measure which best inform clinical decisions in hypertensive patients has yet to be identified. Therefore, hypertension management in frail older adults still represents a 'gap in evidence'. Knowledge of currently available literature is a fundamental prerequisite to develop future research and may help to implement frailty assessment and improve hypertension management in this vulnerable population. Given these premises, we present a narrative review illustrating the most relevant issues that are a matter of debate and that should be addressed in future studies.

Aims Indications, methodology, and diagnostic criteria for carotid sinus massage (CSM) and tilt testing (TT) have been standardized by the 2018 Guidelines on Syncope of the European Society of Cardiology. Aim of this study was to assess their effectiveness in a large cohort which reflects the performance under ‘real-world’ conditions. Methods and results We analysed all patients who had undergone CSM and TT in the years 2003–2019 for suspected reflex syncope. Carotid sinus massage was performed according to the ‘Method of Symptoms’. Tilt testing was performed according to the ‘Italian protocol’ which consists of a passive phase followed by a sublingual nitroglycerine phase. For both tests, positive test was defined as reproduction of spontaneous symptoms in the presence of bradycardia and/or hypotension. Among 3293 patients (mean age 73 ± 12 years, 48% males), 2019 (61%) had at least one test positive. A bradycardic phenotype was found in 420 patients (13%); of these, 60% were identified by CSM, 37% by TT, and 3% had both test positive. A hypotensive phenotype was found in 1733 patients (53%); of these, 98% were identified by TT and 2% had both TT and CSM positive. Conclusion The overall diagnostic yield of the tests in patients >40-year-old with suspected reflex syncope was 61%. Both CSM and TT are useful for identifying those patients with a bradycardic phenotype, whereas CSM has a limited value for identifying the hypotensive phenotype. Since the overlap of responses between tests is minimal, both CSM and TT should be performed in every patient over 40 years receiving investigation for unexplained but possible reflex syncope.

Orthostatic hypotension (OH) is an abnormal blood pressure response to standing, which is associated with an increased risk of adverse outcomes such as syncope, falls, cognitive impairment, and mortality. Medical therapy is one the most common causes of OH, since numerous cardiovascular and psychoactive medications may interfere with the blood pressure response to standing, leading to drug-related OH. Additionally, hypotensive medications frequently overlap with other OH risk factors (e.g., advanced age, neurogenic autonomic dysfunction, and comorbidities), thus increasing the risk of symptoms and complications. Consequently, a medication review is recommended as a first-line approach in the diagnostic and therapeutic work-up of OH, with a view to minimizing the risk of drug-related orthostatic blood pressure impairment. If symptoms persist after the review of hypotensive medications, despite adherence to non-pharmacological interventions, specific drug treatment for OH can be considered. In this narrative review we present an overview of drugs acting on the cardiovascular and central nervous system that may potentially impair the orthostatic blood pressure response and we provide practical suggestions that may be helpful to guide medical therapy optimization in patients with OH. In addition, we summarize the available strategies for drug treatment of OH in patients with persistent symptoms despite non-pharmacological interventions.

Managing hypertension in syncope patients requires the accurate balancing of hypotensive and cardiovascular risks. On the basis of the available literature, this study analyses the complex inter-relationship between these clinical problems and presents an algorithm strategy to guide hypertension management in patients affected by syncope episodes. A SBP target of 120 mmHg is recommended in patients with a low syncope risk and a high cardiovascular risk. In patients with a high syncope risk and a low cardiovascular risk, and in older (70+) frail individuals, a less intensive treatment is advisable, targeting SBP of 140 mmHg. SBP values up to 160 mmHg can be tolerated in severe frailty or disability.Patients with hypertension and syncope may benefit from team-based care by a 'Blood Pressure Team' including experts on hypertension and syncope and a geriatrician. The team should carry out a multidimensional assessment to balance syncope and cardiovascular risk and develop therapeutic strategies customized to individuals' frailty and functional status.

Fear of falling (FoF) is common in older people and may lead to physical decline, disability, poor quality of life, and falls. Several risk factors for FoF have been identified in cross-sectional studies, but evidence on predictors of its incidence is scarce. We investigated the latter in community-dwelling older people undergoing a comprehensive geriatric assessment at baseline and after a 2-year follow-up.Longitudinal study.Convenience sample of community-dwelling people aged ≥60 years evaluated in an Irish university hospital.Participants were evaluated at baseline (August 2007-May 2009) and after a 2-year follow-up. FoF was measured using the Modified Falls Efficacy Scale. Predictors of incident FoF at 2 years were investigated.At baseline, there were 563 participants (69% female, mean age 73 years). Among individuals that were not fearful at baseline, 105 (18.7%) developed FoF (incident FoF) after a median follow-up of 2.1 years. Individuals reporting incident FoF were older at baseline (P .001), had worse performance in balance and physical function tests, and more frequently needed a walking aid (P .001). Anxiety (P = .012) and depressive symptoms (P .001) were more prevalent, as well as self-reported previous falls (P .001). In multivariate analysis, older age, walking aid use, and a higher burden of depressive symptoms at baseline were predictors of incident FoF.Almost a fifth of older adults using a walking aid and reporting depressive symptoms at baseline developed FoF after 2 years. These identifiable prodromal factors could help design FoF prevention strategies.

Objectives the association between renal function and delirium has not been investigated in older fracture patients. Creatinine is frequently low in these subjects, which may influence the association between delirium and renal function as estimated with creatinine-based formulas. Cystatin C could be a more reliable filtration marker in these patients. Aim to confirm the association between renal function and delirium in older fracture patients comparing creatinine- and cystatin-based estimated glomerular filtration rate (eGFR) Methods patients aged 65+ requiring surgery for traumatic bone fractures were included. Six equations were used to calculate eGFR, based on serum creatinine and/or cystatin C obtained within 24 h of admission: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPIcr, CKD-EPIcys, CKD-EPIcr-cys) and Berlin Initiative Study equations (BIS-1, BIS-2). Delirium was identified with a chart-based method. Results 571 patients (mean age 83) were enrolled. Delirium occurred in the 34% and was associated with a lower eGFR regardless of the equation used. In a multivariable model, the association between moderate renal impairment (eGFR 30–60 ml/min/1.73 m2) and delirium remained significant in patients aged 75–84 and only when estimated with cystatin-based or BIS-1 equations. Only dementia was significantly associated with delirium in subjects 85+. Conclusions in older fracture patients, moderate renal impairment was independently associated with delirium only among subjects aged 75–84, when eGFR was estimated with cystatin-based or BIS 1 equations, and not with the most commonly used equations (MDRD, CKD-EPIcr).

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk.

Background Frailty has been recognized as a major risk factor for adverse perioperative and oncological outcomes in patients with genitourinary malignancies. Yet, the evidence supporting such an association in patients with renal cell carcinoma (RCC) is still sparse. Herein we provide an updated comprehensive overview of the impact of frailty on perioperative and oncologic outcomes in patients undergoing surgery or ablation for RCC. Evidence acquisition A systematic review of the English-language literature was conducted using the MEDLINE (Via PubMed), Web of Science and the Cochrane Library databases according to the principles highlighted by the EAU Guidelines Office and the PRISMA statement recommendations. The review protocol was registered on PROSPERO (CRD42021242516). The overall quality of evidence was assessed according to GRADE recommendations. Evidence synthesis Overall, 18 studies were included in the qualitative analysis. Most of these were retrospective single-centre series including patients undergoing surgery for non-metastatic RCC. The overall quality of evidence was low. A variety of measures were used for frailty assessment, including the Canadian Study of Health and Aging Frailty Index, the five-item frailty index, the Modified Rockwood's Clinical Frailty Scale Score, the Hopkins Frailty score, the Groningen Frailty Index, and the Geriatric nutritional risk index. Sarcopenia was defined based on the Lumbar skeletal muscle mass at cross-sectional imaging, the skeletal muscle index, the total psoas area, or the psoas muscle index. Overall, available studies point to frailty and sarcopenia as potential independent risk factors for worse perioperative and oncological outcomes after surgery or ablation for different RCC stages. Increased patient's frailty was indeed associated with higher risk of perioperative complications, healthcare resources utilization, readmission rates and longer hospitalization periods, as well as potentially lower cancer specific or overall survival. Conclusions Frailty has been consistently associated with worse outcomes after surgery for RCC, reinforcing the value of preoperative frailty assessment in carefully selected patients. Given the low quality of the available evidence (especially in the setting of tumour ablation), prospective studies are needed to standardize frailty assessments and to identify patients who are expected to benefit most from preoperative geriatric evaluation, aiming to optimize decision-making and postoperative outcomes in patients with RCC.

Syncope is a frequent event in the general population. Approximately 1%-2% of all emergency department admissions are due to syncope and at least one third of all people experience fainting in their life. Although consequences of cardiac syncope are generally feared, non-cardiac syncope is much more common and may be associated with severe injuries and quality of life impairment, particularly in older adults. Various diagnostic and therapeutic strategies have been created and implemented over decades, leading to significant improvements in diagnostic accuracy and treatment effectiveness. In recent years, diagnosis and treatment have further evolved according to an innovative approach focused on the hemodynamic mechanism underlying syncope, based upon the assumption that knowledge of syncope mechanism is a prerequisite for effective syncope prevention and treatment. Therefore, a new classification of syncope has been proposed, which defines two main syncope phenotypes with different predominant mechanisms: the hypotensive phenotype, where hypotension or vasodepression prevails, and the bradycardic phenotype, where cardioinhibition prevails. Identification of syncope phenotype - bradycardic or hypotensive/vasodepressive - represents the first step towards a personalized management of syncope, characterized by customized interventions for prevention. The present review is aimed at illustrating these new developments in diagnosis and therapy of non-cardiac syncope within a mechanism-based perspective. Diagnosis and therapy of bradycardic and hypotensive phenotypes are discussed, with a focus on recent evidence.

Background Syncope is a common clinical problem with a sharp rise in the incidence after 70 years. In older patients, syncope is often a diagnostic challenge. It is unclear whether the age at which patients experience syncope for the first time impacts the results of syncope investigation. Purpose To study the influence of early-onset vs. mature-onset syncope on clinical characteristics and final head-up tilt (HUT) diagnosis in a large sample of unexplained syncope patients. Methods Consecutive patients (n=1928) with unexplained syncope after initial evaluation examined with a standard HUT protocol in a syncope unit were stratified into age groups below and above 60 years. Clinical characteristics and the final HUT diagnosis were analysed in relation to self-reported age at first syncope and age at investigation. The distribution of age at first syncope was bimodal with peaks at 15 and 70 years (Figure 1). In the present analysis, patients aged >60 years (n=836) with early-onset (60 years) syncope were compared. Results Vasovagal syncope (VVS) was more common in early-onset syncope, 39% vs 19% (p60 years.Complex syncope etiology (findings suggesting overlap between VVS, OH and/or CSS) was more common among patients with early-onset syncope, 37% vs 26% (p=0.023). No definite HUT-derived diagnosis was more common in mature-onset syncope, 23% vs 13% (p=0.023). Heart failure, 9% vs 2% (p=0.024) and atrial fibrillation, 20% vs 9% (p=0.013) were more common in mature-onset syncope. Prodromes were less common in mature-onset syncope, 26% vs 52% (p Conclusions Mature-onset syncope was more often associated with absence of prodromes, orthostatic hypotension, inconclusive HUT findings and presence of heart failure and atrial fibrillation suggesting cardiac syncope to be the likely cause. Early-onset syncope was associated with presence of prodromes, vasovagal reflex mechanism and complex syncope diagnosis. Lifelong and mature-onset unexplained syncope may have different pathophysiological mechanisms in older patients and aetiologies other than vasovagal syncope should be carefully considered in patients with first-ever syncope in later life. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish heart and lung foundationCrafoord foundation

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents.

Aims Syncope without prodromes in subjects with normal heart and normal electrocardiogram (ECG) is classified as non-classical neurally mediated syncope and is characterized by low adenosine plasma levels (APLs) and frequent asystolic syncope. We assessed the efficacy of theophylline, a non-selective adenosine receptor antagonist, in preventing syncopal events. Methods and results Participants received an implantable cardiac monitor, underwent APL measurement, and received oral theophylline at maximum tolerated dose (starting dose 300 mg b.i.d.). They were compared with a historical cohort of untreated patients with implantable cardiac monitor who had the same inclusion criteria and were balanced with the propensity score (PS) method as regard age, sex, lifetime syncopal episodes, APL, and antihypertensive drugs. Primary endpoint was time to first syncopal recurrence at 24 months. There were 76 patients in the theophylline group and 58 in the control group. Syncope recurred in 25 (33%) patients in the theophylline group and in 27 (47%) patients in the control group, with an estimated 2-year recurrence rate of 33% and 60%, respectively, and a hazard ratio of 0.53 [95% confidence interval (CI), 0.30–0.95; P = 0.034]. Most of the benefit of theophylline is derived from reduction of syncope due to asystolic atrioventricular (AV) block (hazard ratio of 0.13; 95% CI, 0.03–0.58; P = 0.008). Thirty (39%) patients discontinued theophylline after a median of 6.4 (interquartile range 1.7–13.8) months due to side effects. Conclusion Theophylline was effective in preventing recurrences in patients with syncope without prodromes, normal heart, and normal ECG. The benefit was greater in patients with syncope due to asystolic AV block. ClinicalTrials.gov Identifier NCT03803215.

Background Psychogenic pseudosyncope (PPS), a conversion disorder and syncope mimic, accounts for a large proportion of ‘unexplained syncope’. PPS is diagnosed by reproduction of patients’ symptoms during head-up tilt (HUT). Electroencephalogram (EEG), a time consuming and resource intensive technology, is used during HUT to demonstrate absence of cerebral hypoperfusion during transient loss of consciousness (TLOC). Near-infrared spectroscopy (NIRS) is a simple, non-invasive technology for continuous monitoring of cerebral perfusion. We present a series of patients for whom PPS diagnosis was supported by NIRS during HUT. Methods Eight consecutive patients with suspected PPS referred to a syncope unit underwent evaluation. During HUT, continuous beat-to-beat blood pressure (BP), heart rate (HR) and NIRS-derived tissue saturation index (TSI) were measured. BP, HR and TSI at baseline, time of first symptom, presyncope and apparent TLOC were measured. Patients were given feedback and followed for symptom recurrence. Results Eight predominantly female patients (6/8, 75%) aged 31 years (16–54) were studied with (5/8, 63%) having comorbid psychiatric diagnoses, and (5/8, 63%) presenting with frequent episodes of prolonged TLOC with eyes closed (6/8, 75%). All patients experienced reproduction of typical events during HUT. Systolic BP (mmHg) increased from baseline (129.7 (interquartile range [IQR] 124.9–133.4)) at TLOC (153.0 (IQR 146.7–159.0)) (P-value = 0.012). HR (bpm) increased from baseline 78 (IQR 68.6–90.0) to 115.7 (IQR 93.5–127.9) (P-value = 0.012). TSI (%) remained stable throughout, 71.4 (IQR 67.5–72.9) at baseline vs. 71.0 (IQR 68.2–73.0) at TLOC (P-value = 0.484). Conclusions NIRS provides a non-invasive surrogate of cerebral perfusion during HUT. We propose HUT incorporating NIRS monitoring in the diagnostic algorithm for patients with suspected PPS.

Background Older people taking benzodiazepines (BDZs) have higher risk of falling, which is mainly attributed to unfavorable drug-related effects on cognition and psychomotor functioning. BDZs may also have hypotensive effects, but evidence concerning the relationship between BDZs and orthostatic blood pressure (BP) behaviour in older people is scarce. We investigated the effects of BDZs on BP response to an orthostatic active stand test. Methods We performed a retrospective analysis of data from an outpatient research clinic in an Irish university hospital, where people aged 60 or older underwent a comprehensive geriatric assessment between August 2007 and May 2009. Non-invasive beat-to-beat orthostatic BP was measured during active stand, with systolic BP assessed at each 10-second interval. Information on regular BDZs use was collected. Factors independently associated with orthostatic systolic BP were investigated using multiple linear regression. Results Of 624 community-dwelling people who underwent a clinic assessment, orthostatic active stand data was collected in 541. Information on regular BDZs use was available in 538 people. Of 538 participants, mean age was 72.7±7.2, 67.7% were female and 33 (6.1%) reported regular use of BDZs. History of falls (p=0.027) and fear of falling (p Conclusion BDZs may confer higher risk of an immediate systolic BP drop after standing in older people, which may contribute to their known falls risk. BDZ should be avoided in older people at risk of falling.

The rate of syncope in the Emergency Department ranges between 0.9 and 1.7%. Syncope is mostly related to a underlying reflex or orthostatic mechanism. A bradycardic or a hypotensive phenotype, may be identified. The latter is the most common and could be constitutional or drug induced. Consequently, obtaining an accurate drug history is an important step of the initial assessment of syncope. As anti-hypertensive medication might be responsible for orthostatic hypotension, managing hypertension in patients with syncope requires finding an ideal balance between hypotensive and cardiovascular risks. The choice of anti-hypertensive molecule as well as the therapeutic regimen and dosage, influences the risk of syncope. Not only could anti-hypertensive drugs have a hypotensive effect but opioids and psychoactive medications may also be involved in the mechanism of syncope. Proper drug management could reduce syncope recurrences and their consequences.

Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders. Results: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively. Conclusion: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Aims Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P Conclusion This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.

This article aims to give advice on how to identify and manage patients with syncope who are at risk of severe outcomes, that is, at risk of trauma, potentially life-threatening episodes or frequent recurrences reducing quality of life. The first step of syncope diagnostic assessment is to identify patients with cardiac syncope, and once established, these patients must receive the adequate mechanism-specific treatment. If cardiac syncope is unlikely, reflex (neurally mediated) syncope and orthostatic hypotension are the most frequent causes of transient loss of consciousness. For these presentations, efficacy of therapy is largely determined by the mechanism of syncope rather than its aetiology or clinical features. The identified mechanism of syncope should be carefully assessed and assigned either to hypotensive or bradycardic phenotype, which will determine the choice of therapy (counteracting hypotension or counteracting bradycardia). The results of recent trials indicate that ‘mechanism-specific therapy’ is highly effective in preventing recurrences. Established mechanism-specific treatment strategies include withdrawal of hypotensive drugs, applying fludrocortisone and midodrine for the hypotensive phenotype and cardiac pacing in the bradycardic phenotype.

BACKGROUNDWe hypothesized that cardiovascular physiology differs in reflex syncope patients compared with general population, predisposing such subjects to vasovagal reflex.METHODSIn this multicohort cross-sectional study, we compared resting systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and heart rate (HR), collected from 6 community-based cohort studies (64,968 observations) with those from 6 databases of reflex syncope patients (6516 observations), subdivided by age decades and sex.RESULTSOverall, in males with reflex syncope, SBP (−3.4 mmHg) and PP (−9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages >60 years. In females, PP (−6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with males, SBP in females exhibited slower increase until age 40, and then demonstrated steeper increase that continued throughout life.CONCLUSIONThe patients prone to reflex syncope demonstrate a different resting cardiovascular hemodynamic profile characterized by reduced venous return and stroke volume, evidenced by lower SBP and PP, and compensatory increase in HR and vascular resistance, the latter expressed by elevated DBP. The data presented here contribute to our understanding why some subjects with similar demographic characteristics develop reflex syncope and others not.

Introduction Why some individuals with similar demographic characteristics develop syncope during tilt testing (TT) and others do not is unknown and low test sensitivity is claimed. We sought an alternative explanation; resting cardiovascular physiology differs in patients with positive and negative TT. Methods We analyzed age, gender, systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) using three large syncope patient databases comparing tilt-positive with tilt-negative results after excluding orthostatic hypotension. Positive tilt-response, confirming reflex syncope, was defined as reproduction of spontaneous symptoms with characteristic bradycardia and/or hypotension. Impact of demographic, hemodynamic parameters and prevalent hypertension on TT positivity were assessed using logistic regression models. Results Records of 5236 patients (45% males; mean age, 60±22 years; 32% on antihypertensive therapy) were analyzed. TT was positive in 3129 (60%) and tilt-positive patients had lower SBP (127.2±17.9 vs 129.7±18.0 mmHg, p

Aims Tilt testing (TT) is recognized to be a valuable contribution to the diagnosis and the pathophysiology of vasovagal syncope (VVS). This study aimed to assess the influence of age on TT responses by examination of a large patient cohort. Methods and results Retrospective data from three experienced European Syncope Units were merged to include 5236 patients investigated for suspected VVS by the Italian TT protocol. Tilt testing-positivity rates and haemodynamics were analysed across age-decade subgroups. Of 5236 investigated patients, 3129 (60%) had a positive TT. Cardioinhibitory responses accounted for 16.5% of positive tests and were more common in younger patients, decreasing from the age of 50–59 years. Vasodepressor (VD) responses accounted for 24.4% of positive tests and prevailed in older patients, starting from the age of 50–59. Mixed responses (59.1% of cases) declined slightly with increasing age. Overall, TT positivity showed a similar age-related trend (P = 0.0001) and was significantly related to baseline systolic blood pressure (P Conclusions Age significantly impacts the haemodynamic pattern of TT responses, starting from the age of 50. Conversely, TT phase—passive or TNG-potentiated—does not significantly influence the type of response, when age-adjusted. Vagal hyperactivity dominates in younger patients, older patients show tendency to vasodepression.

A structured four-step bedside algorithm, named SponTAneous Nystagmus, Direction, head Impulse test, standiNG (STANDING), has been proposed to differentiate central from peripheral acute vestibulopathy in the Emergency Department (ED). We aimed to evaluate the effective application of STANDING in the management of vertigo in the ED and to define its role in deciding the patient’s pathway after discharge. We retrospectively analysed data from 131 consecutive patients (65% female, mean age 56) undergoing ED visits for a vertigo complaint between April and May 2016. Our study showed that the STANDING algorithm is underused, being performed only in the 18% of patients. The positivity of the STANDING did not influence the choice of the following pathway (e.g. outpatient fast track or discharge). Moreover, a small percentage of patients had a non-audiological diagnosis (mainly presyncope), for which no defined pathways were yet foreseen. Our study emphasized the need for continuous updating with appropriate training courses and the importance of a multidisciplinary assessment of vertigo in the ED.

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21–1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146–2.97]; P P

Optimal blood pressure (BP) control can prevent major adverse health events, but target values are still controversial, especially in older patients with comorbidities, frailty and disability. To evaluate mortality according to BP values in a cohort of older adults enrolled in the Fiesole Misurata Study, after a 6-year follow-up. Living status as of December 31, 2016 was obtained in 385 subjects participating in the Fiesole Misurata Study. Patients' characteristics were analysed to detect predictors of mortality. At baseline, all participants had undergone office BP measurement and a comprehensive geriatric assessment. After a 6-year follow-up, 97 participants had died (25.2%). After adjustment for comorbidities and comprehensive geriatric assessment, mortality was significantly lower for SBP 140–159 mmHg as compared with 120–139 mmHg (HR 0.54, 95% CI 0.33–0.89). This result was also confirmed in patients aged 75 + (HR 0.49, 95% CI 0.29–0.85), and in those with disability (HR 0.36, 95% CI 0.15–0.86) or taking antihypertensive medications (HR 0.49, 95% CI 0.28–0.86). An intensive BP control may lead to greater harm than benefit in older adults. Indeed, the European guidelines recommend caution in BP lowering in older patients, especially if functionally compromised, to minimize the risk of hypotension-related adverse events. After a 6-year follow-up, mortality risk was lower in participants with SBP 140–159 mmHg as compared with SBP 120–139 mmHg, in the overall population and in the subgroups of subjects aged 75 + , with a disability or taking anti-hypertensive medications.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Background Cardiac pacing is the treatment of choice for cardioinhibitory carotid sinus syndrome (CSS), but syncope recurrence occurs in up to 20% of patients within 3 years. The present study aims at assessing incidence and identifying predictors of syncope recurrence in patients receiving pacing therapy for CSS. Methods The Syncope Clinics of two large regional hospitals in Northern Italy, both following European Syncope Guidelines, combined to perform this study. Retrospective analysis of 3127 consecutive patients undergoing carotid sinus massage (CSM) was performed 2004–2014. Ten-second supine and standing CSM was systematically assessed in patients aged >40 years with suspected reflex syncope as part of the initial evaluation. Syncope recurrence was investigated in those paced for CSS having >6 months' available follow-up. Data were collected from clinical records and patient interviews. Results CSS was diagnosed in 261 patients (8.3%). Pacemakers were implanted in 158, with follow-up data available in 112: 19 (17%) experienced 73 syncope recurrences during a mean follow-up of 89 ± 42 months, yielding an incidence of 0.5 episodes per patient/year. Prodrome, predisposing situations preceding syncope and chronic nitrate therapy were more frequent in patients reporting recurrence. Prodrome and predisposing situations remained independent predictors of post-implantation recurrence on multivariable analysis. Conclusions CSS is a frequent cause of syncope, if CSM is performed during the initial evaluation. Most patients treated by pacing remain asymptomatic during long-term follow-up. In those who have recurrence, its incidence is very low. Prodrome and predisposing situations are predictors of post-implantation recurrence, suggesting presence of hypotensive susceptibility.

Background Psychogenic pseudosyncope (PPS) is a conversion disorder that often mimics syncope, is commonly referred to cardiology clinics and accounts for a large proportion of patients admitted with “unexplained syncope”. Unlike syncope, PPS is characterized by normal blood pressure (BP) and heart rate (HR) values at TLOC inferring the absence of cerebral hypoperfusion. The current gold standard for the diagnosis of PPS is the reproduction of patients' symptoms during a head-up tilt test (HUTT) with concurrent electroencephalogram (EEG) monitoring showing normal haemodynamic and brainwave measurements. However, EEG is time consuming, resource intensive and many syncope units lack ready access, thereby solely relying on absence of peripheral haemodynamic changes to diagnose PPS. Purpose Near-infrared spectroscopy (NIRS) is a non-invasive technology used for continuous monitoring of cerebral oxygenation. Measuring adequacy of tissue oxygenation is an appropriate surrogate for cerebral perfusion. In this study, we present a case series of patients for whom the diagnosis of PPS was confirmed by NIRS during TLOC. We propose use of NIRS in routine clinical assessment of suspected PPS. Methods We describe nine consecutive patients with suspected PPS referred to a dedicated syncope unit for investigation of recurrent unexplained syncope. All patients underwent evaluation in accordance with European Society of Cardiology guidelines including HUTT. Continuous beat-to-beat BP and HR measurements were recorded using finger plethysmography. In addition, continuous NIRS-derived tissue saturation index (TSI) - a measure of percentage oxygenation - was recorded using an optical sensor applied to the left lateral forehead to assess cerebral perfusion. Absolute values of BP, HR and TSI at baseline, time of first symptom onset, presyncope and apparent TLOC were recorded. The evaluation was diagnostic for PPS when apparent TLOC occurred in the absence of typical haemodynamic or cerebral perfusion changes. Results The median age was 35 years (range 14–54). Clinical features were consistent with those previously described in PPS literature - female preponderance, comorbid psychiatric diagnosis, frequent attack history, with prolonged TLOC and eyes closed during events. During HUTT, all patients experienced an apparent TLOC which they recognised as reproductive of typical events. BP and HR measurements increased significantly at time of TLOC. There was no significant change in TSI at any of the time points throughout HUTT. (Figure 1 shows averaged absolute values of systolic and diastolic BP, HR and TSI with median values represented by thickened lines.) Figure 1. Measurements during HUTT Conclusion NIRS is readily available, easily accessible and provides an appropriate surrogate measure of cerebral perfusion during HUTT. We propose that HUTT incorporating concurrent NIRS monitoring will enhance diagnostic yield and patient management providing important biofeedback.

Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study “Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives”. This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.

Older people taking benzodiazepines (BDZs) have higher risk of falling, which is mainly attributed to cognitive and psychomotor effects. BDZs may also have hypotensive effects. We investigated the association between BDZs and orthostatic blood pressure behaviour in older people.We retrospectively analysed data from an outpatient clinic where people aged 60 or older underwent a geriatric assessment. Non-invasive beat-to-beat orthostatic systolic blood pressure (SBP) was assessed at regular time intervals before and after an active stand test. We compared clinical characteristics between BDZs users and non-users and also investigated if BDZs use was an independent predictor of baseline SBP. Factors associated with SBP change were investigated using a repeated measures general linear model.Of 538 participants (67.7% female, mean age 72.7), 33 (6.1%) reported regular BDZs use. BDZ users had lower baseline SBP (149 versus 161 mmHg, P 0.05). Multiple linear regression confirmed BDZs use as independent predictor of baseline SBP in N = =538. At 10 s post-stand, the SBP difference between BDZs use groups became maximum (21 mmHg); at this point, SBP still seemed to be decreasing in BDZ-users, whereas in controls it seemed to be recovering. After adjustment (age, sex, hypertension, frailty, comorbidity, antihypertensives), BDZs were associated with greater SBP reduction between baseline and 10 s post-stand (P 0.05).Older people taking BDZs may have a higher risk of orthostatic hypotension, perhaps due to an exaggerated immediate BP drop. This adds to other BDZ-related falls risks. BDZs should be avoided in older people at risk of falling.

Background Patients affected by syncope without or with very short (≤5 s) prodrome with normal heart and normal ECG have been seen to present low plasma adenosine levels. We investigated whether chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, results in clinical benefit. Methods In a consecutive case-series of 16 patients (mean age 47 ± 25 years, 9 females) who had ECG documentation of asystolic syncope, we compared the incidence of syncopal recurrence during a period without and a period with tailored theophylline therapy. Results During a median of 60 months before ECG documentation of the index episode, the patients had a median of 2 syncopes per year. During the 6 months of the study phase without therapy, the patients had a median of 2.6 syncopes per year, p = 0.63. During the 23 months of the study phase with theophylline, the patients had a median of 0.4 syncopes per year, p = 0.005 vs history and p = 0.005 vs no therapy. In the 13 patients who had an implantable loop recorder during both study phases, the incidence of asystolic episodes > 3 s decreased from 9.6 per year to 1.1 per year, p = 0.0007. During theophylline treatment, syncope recurred in 1/5 (20%) patients who had an idiopathic atrioventricular block as the index event versus 9/11 (81%) patients who had a sinus arrest, p = 0.005. Conclusion Theophylline is effective in reducing syncopal burden in patients with syncope without prodromes with normal heart and normal ECG. Its efficacy is greater in those with idiopathic atrioventricular block.

To evaluate the characteristics of patients referred for dizziness to a Syncope Unit. This is a retrospective study. Of 491 patients referred to the Syncope Unit of Careggi Hospital in 2015, 198 (40.3%) who experienced dizziness alone or associated with a history of transient loss of consciousness were enrolled. All the patients underwent an initial evaluation according to the European Society of Cardiology guidelines on syncope. We compared the clinical characteristics and final diagnosis of patients referred for dizziness alone (n = 64) to those of patients with dizziness and history of transient loss of consciousness (n = 134). The study population had a mean age of 62 ± 20 years (range 16–96 years) and 101 (51%) were female. A final diagnosis of pre-syncope was made in about the 80% of the patients without a previous history of transient loss of consciousness. In this group, other diagnoses were benign paroxysmal positional vertigo (6.3%), transient ischemic attack (4.7%) or psychogenic dizziness (7.8%). Syncope was diagnosed in the 82.7% of the patients with dizziness and history of transient loss of consciousness. Dizziness was the main reason for referral to the Syncope Unit in almost one-third of the patients, in whom pre-syncope was the most frequent final diagnosis. Otological, neurological and psychiatric disorders should be also considered as differential diagnosis, highlighting the importance of a multidisciplinary approach.

Thirty years ago Tilt Testing (TT) was described as a tool in the diagnostic work-up of vasovagal syncope; after its initial success, some flaws have become evident. The concept of hypotensive susceptibility has provided the test a new relevance, shifting from diagnosis only, to therapeutic management. Carotid Sinus Massage (CSM) was introduced at the beginning of the XX century; the technique has evolved over years, whereas the concept of carotid sinus syndrome (CSS) has remained unchanged and uncontested for more than half a century. Nowadays, CSS is a matter of debate, with new classifications and criteria coming on the scene. Recently, a common central etiological mechanism has been hypothesized for reflex syncope, manifesting as CSS, vasovagal syncope or both. In this context, TT and CSM acquire an important role in clinical practice, being essential for a complete diagnosis and treatment. Recalling their historical background, the present paper illustrates an actual interpretation of TT and CSM.

In cardio-inhibitory Carotid Sinus Syndrome (CI-CSS), syncopal recurrence is expected to occur in up to the 20% of patients after pacing therapy. The present study analyzes post-implantation syncopal recurrence in CI-CSS, to identify predictors of recurrence. We retrieved electronic records