The Effects of Pain and Analgesic Medications on Blood Pressure.

PURPOSE OF REVIEW: To review the blood pressure (BP) effects of pain and analgesic medications and to help interpret BP changes in people suffering from acute or chronic pain. RECENT FINDINGS: Acute pain evokes a stress response which prompts a transient BP increase. Chronic pain is associated with impaired regulation of cardiovascular and analgesia systems, which may predispose to persistent BP elevation. Also analgesics may have BP effects, which vary according to the drug class considered. Data on paracetamol are controversial, while multiple studies indicate that non-steroidal anti-inflammatory drugs may increase BP, with celecoxib showing a lesser impact. Hypotension has been reported with opioid drugs. Among adjuvants, tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors could be pro-hypertensive due to potentiation of adrenergic transmission. Pain and analgesics may induce a clinically significant BP destabilization. The implications on hypertension incidence and BP control remain unclear and should be explored in future studies.

Blood pressure and long-term mortality in older patients: results of the Fiesole Misurata Follow-up Study.

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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. CONCLUSIONS: 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.

Evaluation of renal function in the elderly, not as easy as it seems: a review.

In the elderly assessment of renal function by glomerular filtration rate estimation is crucial for diagnostic, therapeutic and prognostic purposes. Our aim is to illustrate the different formulas available and their respective advantages and disadvantages.

Effects of the implementation of the dynamic silver code in the emergency department.

BACKGROUND: Older persons accessing the Emergency Department (ED) spend more time and are at increased risk of poor outcomes. The Dynamic Silver Code (DSC), based on administrative data, predicts mortality of 75+ subjects visiting the ED. OBJECTIVE: To evaluate the effects of the implementation of the DSC in the ED. METHODS: A pre-post comparison was conducted in the ED of a community hospital in Florence, Italy before and after the DSC was fully implemented. In the post-DSC phase, a clinical decision tree was applied: patients at low-mild risk (DSC class I and II) were assigned to Internal Medicine, those at moderate risk (class III) to Geriatrics, and those at high risk (class IV) required geriatric consultation before assignment. Outcome measures were ED length of stay (LOS) and, in patients admitted to Geriatrics, weight of the Diagnosis Related Groups (DRG), hospital LOS, and mortality. RESULTS: 7,270 patients were enrolled in the pre-DSC and 4,725 in the post-DSC phase. ED LOS decreased from a median of 380 [206, 958] in the pre-DSC to 318 [178, 655] min in the post-DSC period (p<0.001). Class III represented the largest share of admissions to Geriatrics in the post-DSC period (57.7 % vs. 38.3 %; p<0.001). In patients admitted to Geriatrics, hospital LOS decreased by one day (p = 0.006) between the two study periods, with greater DRG weight and comparable mortality. CONCLUSIONS: Application of the DSC seemed to ease patient flow and to reduce LOS of older patients in the ED and increased appropriateness of admissions to Geriatrics.

Screening for cognitive impairment in older adults with hypertension: the HYPER-COG study.

Hypertension is a major risk factor for dementia. Yet, the most suitable cognitive screening test for hypertensive patients has yet to be identified. This study investigated cognitive impairment in hypertensive older adults and compared the discriminative ability of the most widely used cognitive screening tests. The study involved hypertensive patients aged 65+ without prior diagnosis of cognitive impairment, from the Hypertension Clinic of Careggi Hospital, Florence, Italy. Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), MiniCog and Clock Drawing Test (CDT) were administered, using a comprehensive neuropsychological assessment as gold standard. The ROC curve analysis and the paired chi-square test were used to compare the discriminative ability, sensitivity and specificity for cognitive impairment of the different screening instruments. Cognitive impairment was diagnosed in 37% of 94 participants (mean age 76, 55% female), mainly involving attention and executive functions. The MoCA (AUC = 0.746), the MMSE (AUC = 0.689) and the MiniCog (AUC = 0.684) showed similar ability in detecting cognitive impairment, while the CDT had a poorer discriminative capacity (AUC = 0.535). The sensitivity of MoCA (80%) and of MMSE/MiniCog combination (74%) was higher in comparison with MiniCog alone (49%, p = 0.007 and 0.004, respectively), while MiniCog achieved the highest specificity (88%, p < 0.001 vs all). Cognitive impairment was detected in more than one-third of hypertensive older adults without prior diagnosis of dementia. MoCA, MMSE and MiniCog showed similar discriminative ability for cognitive impairment, with MoCa and MMSE showing greater sensitivity and MiniCog the highest specificity.

Towards Automated Assessment of Frailty Status Using a Wrist-Worn Device.

Wearable sensors potentially enable monitoring the user's physical activity in daily life. Therefore, they are particularly appealing for the evaluation of older subjects in their environment, to capture early signs of frailty and mobility-related problems. This study explores the use of body-worn accelerometers for automated assessment of frailty during walking activity. Experiments involved 34 volunteers aged 70+, who were initially screened by geriatricians for the presence of frailty according to Fried's criteria. After screening, the volunteers were asked to walk 60 m at preferred speed, while wearing two accelerometers, one positioned on the lower back and the other on the wrist. Sensor-derived signals were analyzed independently to compare the ability of the two signals (wrist vs. lower back) in frailty status assessment. A gait detection technique was applied to identify segments made of four gait cycles. These segments were then used as input to compute 25 features in time and time-frequency domains, the latter by means of the Wavelet Transform. Finally, five machine learning models were trained and evaluated to classify subjects as robust or non-robust (i.e., pre-frail or frail). Gaussian naive Bayes applied to the features derived from the wrist sensor signal identified non-robust subjects with 91% sensitivity and 82% specificity, compared to 87% sensitivity and 64% specificity achieved with the lower back sensor. Results demonstrate that a wrist-worn accelerometer provides valuable information for the recognition of frailty in older adults, and could represent an effective tool to enable automated and unobtrusive assessment of frailty.

COVID-19, Vulnerability, and Long-Term Mortality in Hospitalized and Nonhospitalized Older Persons.

OBJECTIVE: Studies suggesting that vulnerability increased short-term mortality in older patients with COVID-19 enrolled hospitalized patients and lacked COVID-negative comparators. Aim of this study was to examine the relationship between frailty and 1-year mortality in older patients with and without COVID-19, hospitalized and nonhospitalized. DESIGN: Cohort study. SETTING AND PARTICIPANTS: Patients over 75 years old accessing the emergency departments (ED) were identified from the ED archives in Florence, Italy. METHODS: Vulnerability status was estimated with the Dynamic Silver Code (DSC). COVID-19 hospital discharges (HC+) were compared with non-COVID-19 discharges (HC-). Linkage with a national COVID-19 registry identified nonhospitalized ED visitors with (NHC+) or without COVID-19 (NHC-). RESULTS: In 1 year, 48.4% and 33.9% of 1745 HC+ and 15,846 HC- participants died (P < .001). Mortality increased from 27.5% to 64.0% in HC+ and from 19.9% to 51.1% in HC- across DSC classes I to IV, with HC+ vs HC- hazard ratios between 1.6 and 2.2. Out of 1039 NHC+ and 18,722 NHC- participants, 18% and 8.7% died (P < .001). Mortality increased from 14.2% to 46.7% in NHC+ and from 2.9% to 26% in NHC- across DSC; NHC+ vs NHC- hazard ratios decreased from 5.3 in class I to 2.0 in class IV. CONCLUSIONS AND IMPLICATIONS: In hospitalized older patients, mortality increases with vulnerability similarly in the presence and in the absence of COVID-19. In nonhospitalized patients, vulnerability-associated excess mortality is milder in individuals with than in those without COVID-19. The disease reduces survival even when background risk is low. Thus, apparently uncomplicated patients deserve closer clinical monitoring than commonly applied.

Estimating Prognosis and Frailty in Persons Aged ≥75 Years in the Emergency Department: Further Validation of Dynamic Silver Code.

OBJECTIVES: To assess concurrent validity of the Dynamic Silver Code (DSC), a tool based on administrative data that predicts prognosis in older adults accessing the emergency department (ED), in terms of association with markers of poor functional and cognitive status. DESIGN: Cross-sectional. SETTING AND PARTICIPANTS: Data were obtained in the AIDEA study, which enrolled a cohort of ≥75-year-old patients, accessing the ED of 2 hospitals in Florence, Italy. METHODS: The DSC score and classes (I to IV, corresponding to an increasing risk of death) were obtained from administrative data. Information on health and functional status prior to ED access were collected from face-to-face, direct, or proxy interviews. The 4AT test was administered to screen for possible delirium. Bivariate comparisons of the prevalence of each functional and cognitive marker across 4 DSC classes were performed. Multinomial logistic regression was used to assess the multivariable risk of being in II, III, or IV DSC class vs I. RESULTS: Among 3358 participants (mean age 83 years, men 44%), 32.9%, 30.3%, 19.5%, and 17.2% were in DSC class I, II, III, and IV. Preadmission abnormal functional and cognitive conditions, and delirium in the ED, were increasingly more common from DSC class I through IV (P < .001). In particular, the prevalence of total inability to walk increased from 2.9% (class I) to 23.4% (class IV). In multivariable analyses, this was the strongest predictor of being in progressively worse DSC classes, whereas feeling of exhaustion, reporting of serious falls, weight loss, and severe memory loss or diagnosis of dementia gave some contribution. CONCLUSIONS AND IMPLICATIONS: The ability of the DSC to predict survival in older persons appears to rely on its prevailing association with markers of functional impairment. These results may support clinical use of the tool.

Long-term Survival After Hospital Admission in Older Italians: Comparison Between Geriatrics and Internal Medicine Across Different Discharge Diagnoses and Risk Status.

BACKGROUND: In randomized clinical trials, compared to Internal Medicine, admission to Geriatrics improved clinical outcomes of frail older patients accessing the Emergency Department (ED). Whether this advantage is maintained also in the "real world" is uncertain. We compared long-term survival of patients admitted to Geriatrics or Internal Medicine wards after stratification for background risk and across a variety of discharge diagnoses. METHOD: Data were derived from the "Silver Code National Project," an observational study of 180,079 unselected 75+ years old persons, admitted via the ED to Internal Medicine (n = 169,717, 94.2%) or Geriatrics (n = 10,362) wards in Italy. The Dynamic Silver Code (DSC), based on administrative data, was applied to balance for background risk between participants admitted to Geriatrics or Internal Medicine. RESULTS: One-year mortality was 33.7%, lower in participants discharged from Geriatrics (32.1%) than from Internal Medicine (33.8%; p < .001), and increased progressively across four DSC risk classes (p < .001). Admission to Geriatrics was associated with survival advantage in DSC class II to IV participants, with HR (95% CI) of 0.88 (0.83-0.94), 0.86 (0.80-0.92), and 0.92 (0.86-0.97), respectively. Cerebrovascular diseases, cognitive disorders, and heart failure were the discharge diagnoses with the widest survival benefit from admission to Geriatrics, which was mostly observed in DSC class III. CONCLUSIONS: Admission to Geriatrics may provide long-term survival benefit in subjects who, based on the DSC, may be considered at an intermediate risk. Specific clinical conditions should be considered in the ED to improve selection of patients to be targeted for Geriatrics admission.

Low Creatinine Potentially Overestimates Glomerular Filtration Rate in Older Fracture Patients: A Plea for an Extensive Use of Cystatin C?

AIM: 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. METHODS: 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. RESULTS: 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 (p<0.001), while cystatin C remained stable. According to creatinine-based formulas, eGFR was < 60 mL/min/1.73 m2 in 29-30% at baseline and only in 17% participants in the post-operative period. Conversely, according to equations including cystatin C, eGFR was < 60 mL/min/1.73 m2 in half to three-quarters of the sample at all assessments. CONCLUSIONS: In 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.

Renal function and delirium in older fracture patients: different information from different formulas?

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).

Clavaminols A-F, novel cytotoxic 2-amino-3-alkanols from the ascidian Clavelina phlegraea.

The chemical investigation of the Mediterranean ascidian Clavelina phlegraea has led to the isolation of six new 2-amino-3-alkanol derivatives, clavaminols A-F (1-6). Their stereostructures were established by analysis of spectroscopic data and chemical conversion. Clavaminols A, B, C, and F were tested for their cytotoxic and pro-apoptotic properties and clavaminol A was shown to be the more potent cytotoxic compound of this series inducing cell death through activation of the apoptotic machinery.

Damipipecolin and damituricin, novel bioactive bromopyrrole alkaloids from the Mediterranean sponge Axinella damicornis.

Two new bromopyrrole alkaloids, damipipecolin (1) and damituricin (2), have been isolated from the Mediterranean sponge Axinella damicornis, and their structures established through spectroscopic methods. Compounds 1 and 2 extend the structural variety of the so far known pyrrole alkaloids; in these compounds, the 4-bromopyrrole 2-carboxylic acid is directly condensed with a non-protein cyclic alpha-amino acid, the (2R, 4R)-trans-4-hydroxypipecolic acid and (2R, 4R)-cis-N,N'-dimethyl-4-hydroxyproline (D-turicine) in 1 and 2, respectively. Compounds 1 and 2 were found to display a modulating effect of the serotonin receptor activity in vitro.