Pulmonary Vasodilator and Inodilator Drugs in Cardiac Surgery: A Systematic Review With Bayesian Network Meta-Analysis.

OBJECTIVE: The authors performed a systematic review to evaluate the effect of pharmacologic therapy on pulmonary hypertension in the perioperative setting of elective cardiac surgery (PROSPERO CRD42023321041). DESIGN: Systematic review of randomized controlled trials with a Bayesian network meta-analysis. SETTING: The authors searched biomedical databases for randomized controlled trials on the perioperative use of inodilators and pulmonary vasodilators in adult cardiac surgery, with in-hospital mortality as the primary outcome and duration of ventilation, length of stay in the intensive care unit, stage 3 acute kidney injury, cardiogenic shock requiring mechanical support, and change in mean pulmonary artery pressure as secondary outcomes. PARTICIPANTS: Twenty-eight studies randomizing 1,879 patients were included. INTERVENTIONS: Catecholamines and noncatecholamine inodilators, arterial pulmonary vasodilators, vasodilators, or their combination were considered eligible interventions compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS: Ten studies reported in-hospital mortality and assigned 855 patients to 12 interventions. Only inhaled prostacyclin use was supported by a statistically discernible improvement in mortality, with a number-needed-to-treat estimate of at least 3.3, but a wide credible interval (relative risk 1.26 × 10-17 - 0.7). Inhaled prostacyclin and nitric oxide were associated with a reduction in intensive care unit stay, and none of the included interventions reached a statistically evident difference compared to usual care or placebo in the other secondary clinical outcomes. CONCLUSIONS: Inhaled prostacyclin was the only pharmacologic intervention whose use is supported by a statistically discernible improvement in mortality in the perioperative cardiac surgery setting as treatment of pulmonary hypertension. However, available evidence has significant limitations, mainly the low number of events and imprecision.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Exercise in Older Adults to Prevent Depressive Symptoms at the Time of Covid-19: Results of a Randomized Controlled Trial with Follow-Up.

Background: This study aimed to verify, through a randomized controlled trial, whether a medium-intensity mixing/aerobic/anaerobic exercise (accessible to older adults even with mild chronic diseases) can effectively counteract depressive episodes. A characteristic of the trial was that the follow-up coincided (unscheduled) with the lockdown due to Covid-19. Methods: Participants (N=120) were randomized into an intervention group, performing physical exercise, and a control group. Participants, aged 65 years and older, belonged to both genders, living at home, and cleared a medical examination, were evaluated with a screening tool to detect depressive episodes, the PHQ9, at pre-treatment, end of the trial (12-week), and follow-up (48-week). Results: A decrease in the frequency of depressive episodes after the trial (T1) was found in both groups; however, a statistically significant difference was observed only in the control group (p=0.0039). From T1 to follow-up (conducted during the lockdown), the frequency of depressive episodes increased in the control group, reaching a frequency equal to the time of study entry (p=0.788). In the experimental group, the frequency of depressive episodes did not change at the end of the trial but reached a statistically significant difference compared to the start of the study (p = 0.004) and was higher than the control group (p=0.028). Conclusion: Moderate-intensity physical exercise can be conducted safely, benefitting older adults even suffering from mild chronic disorders. Physical exercise seems to guarantee a long-term preventive effect towards depressive symptoms, especially in serious stressful situations such as the lockdown due to the Covid-19 pandemic.

Moderate Exercise Improves Cognitive Function in Healthy Elderly People: Results of a Randomized Controlled Trial.

BACKGROUND: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment. OBJECTIVE: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance. DESIGN: RCT with parallel and balanced large groups. SETTING: Academic university hospital and Olympic gyms. SUBJECTS: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity. METHODS: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of "life movements", strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales. RESULTS: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046). CONCLUSION: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes.Clinical Trials Registration No: NCT03858114.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality.

OBJECTIVE: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: Two hundred fifty-one physicians from 46 countries. INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality.

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.

Healthcare-associated respiratory infections in intensive care unit can be reduced by a hand hygiene program: A multicenter study.

PURPOSE: Healthcare-associated respiratory tract infections are common and markedly affect the quality of life and mortality, as well as increasing costs for health systems due to prolonged hospitalisation. This study aimed to assess the change in both level and trend of respiratory tract infections after a specific hand hygiene program for intensive care unit (ICU) staff. MATERIALS AND METHODS: The infection data collection was carried out from January 2013 to August 2014. The hand hygiene program started in December 2013. To analyse the change in level and trend of infections after the intervention, the Interrupted Time Series method was used. Chi-square test was used to compare the incidence of respiratory tract infections before and after the intervention. RESULTS: A total of 825 patients were hospitalised in three Italian ICUs. The infection level was significantly decreased by 36.3 infections per 1000 device-days after the intervention. The infection trend was also decreased of about 1 infection per month. CONCLUSIONS: After the hand hygiene program a decreased level of infection was found. Continuous performance feedback should be provided to promote a long-term adherence to the guidelines. Organisational and individual risk factors must be individuated and correctly managed to increase quality of practice.

Randomized Evidence for Reduction of Perioperative Mortality: An Updated Consensus Process.

OBJECTIVE: Of the 230 million patients undergoing major surgical procedures every year, more than 1 million will die within 30 days. Thus, any nonsurgical interventions that help reduce perioperative mortality might save thousands of lives. The authors have updated a previous consensus process to identify all the nonsurgical interventions, supported by randomized evidence, that may help reduce perioperative mortality. DESIGN AND SETTING: A web-based international consensus conference. PARTICIPANTS: The study comprised 500 clinicians from 61 countries. INTERVENTIONS: A systematic literature search was performed to identify published literature about nonsurgical interventions, supported by randomized evidence, showing a statistically significant impact on mortality. A consensus conference of experts discussed eligible papers. The interventions identified by the conference then were submitted to colleagues worldwide through a web-based survey. MEASUREMENTS AND MAIN RESULTS: The authors identified 11 interventions contributing to increased survival (perioperative hemodynamic optimization, neuraxial anesthesia, noninvasive ventilation, tranexamic acid, selective decontamination of the gastrointestinal tract, insulin for tight glycemic control, preoperative intra-aortic balloon pump, leuko-depleted red blood cells transfusion, levosimendan, volatile agents, and remote ischemic preconditioning) and 2 interventions showing increased mortality (beta-blocker therapy and aprotinin). Interventions then were voted on by participating clinicians. Percentages of agreement among clinicians in different countries differed significantly for 6 interventions, and a variable gap between evidence and clinical practice was noted. CONCLUSIONS: The authors identified 13 nonsurgical interventions that may decrease or increase perioperative mortality, with variable agreement by clinicians. Such interventions may be optimal candidates for investigation in high-quality trials and discussion in international guidelines to reduce perioperative mortality.

Outcome of cardiac surgery in patients with low preoperative ejection fraction.

BACKGROUND: In patients undergoing cardiac surgery, a reduced preoperative left ventricular ejection fraction (LVEF) is common and is associated with a worse outcome. Available outcome data for these patients address specific surgical procedures, mainly coronary artery bypass graft (CABG). Aim of our study was to investigate perioperative outcome of surgery on patients with low pre-operative LVEF undergoing a broad range of cardiac surgical procedures. METHODS: Data from patients with pre-operative LVEF ≤40 % undergoing cardiac surgery at a university hospital were reviewed and analyzed. A subgroup analysis on patients with pre-operative LVEF ≤30 % was also performed. RESULTS: A total of 7313 patients underwent cardiac surgery during the study period. Out of these, 781 patients (11 %) had a pre-operative LVEF ≤40 % and were included in the analysis. Mean pre-operative LVEF was 33.9 ± 6.1 % and in 290 patients (37 %) LVEF was ≤30 %. The most frequently performed operation was CABG (31 % of procedures), followed by mitral valve surgery (22 %) and aortic valve surgery (19 %). Overall perioperative mortality was 5.6 %. Mitral valve surgery was more frequent among patients who did not survive, while survivors underwent more frequently CABG. Post-operative myocardial infarction occurred in 19 (2.4 %) of patients, low cardiac output syndrome in 271 (35 %). Acute kidney injury occurred in 195 (25 %) of patients. Duration of mechanical ventilation was 18 (12-48) hours. Incidence of complications was higher in patients with LVEF ≤30 %. Stepwise multivariate analysis identified chronic obstructive pulmonary disease, pre-operative insertion of intra-aortic balloon pump, and pre-operative need for inotropes as independent predictors of mortality among patients with LVEF ≤40 %. CONCLUSIONS: We confirmed that patients with low pre-operative LVEF undergoing cardiac surgery are at higher risk of post-operative complications. Cardiac surgery can be performed with acceptable mortality rates; however, mitral valve surgery, was found to be associated with higher mortality rates in this population. Accurate selection of patients, risk/benefit evaluation, and planning of surgical and anesthesiological management are mandatory to improve outcome.

Mortality in Multicenter Critical Care Trials: An Analysis of Interventions With a Significant Effect.

OBJECTIVES: We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians' opinion and usual practice for the selected interventions. DATA SOURCES: MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. STUDY SELECTION: We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. DATA EXTRACTION: For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. DATA SYNTHESIS: We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. CONCLUSIONS: We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.

Preoperative intra-aortic balloon pump to reduce mortality in coronary artery bypass graft: a meta-analysis of randomized controlled trials.

INTRODUCTION: The intra-aortic balloon pump is routinely used in cardiac surgery; however, its impact on outcome is still a matter of debate and several randomized trials have been published recently. We perform an updated meta-analysis of randomized controlled trials that investigated the use of preoperative intra-aortic balloon pump in adult patients undergoing coronary artery bypass grafting. METHODS: Potentially eligible trials were identified by searching the Medline, Embase, Scopus, ISI Web of Knowledge and The Cochrane Library. Searches were not restricted by language or publication status and were updated in August 2014. Randomized controlled trials on preoperative intra-aortic balloon pump in patients undergoing coronary artery bypass grafting either with or without cardiopulmonary bypass were identified. The primary end point was mortality at the longest follow-up available and the secondary end point was 30-day mortality. RESULTS: The eight included randomized clinical trials enrolled 625 patients (312 to the intra-aortic balloon pump group and 313 to control). The use of intra-aortic balloon pump was associated with a significant reduction in the risk of mortality (11 of 312 (3.5%) versus 33 of 313 (11%), risk ratio = 0.38 (0.20 to 0.73), P for effect = 0.004, P for heterogeneity = 0.7, I-square = 0%, with eight studies included). The benefit on mortality reduction was confirmed restricting the analysis to trials with low risk of bias, to those reporting 30-day follow-up and to patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. CONCLUSIONS: Preoperative intra-aortic balloon pump reduces perioperative and 30-day mortality in high-risk patients undergoing elective coronary artery bypass grafting.

Patients with carotid atherosclerosis who underwent or did not undergo carotid endarterectomy: outcome on mood, cognition and quality of life.

BACKGROUND: To compare the six-month outcome on mood, cognition and quality of life (QoL) in patients with severe carotid atherosclerosis (CA) who underwent carotid endarterectomy (CEA) with subjects who refused treatment. METHODS: Cohort study on consecutive inpatients with CA (stenosis ≥ 50 %) (N = 46; age 72.56 ± 7.26; male 65.2 %). Intervention cohort: subjects who decided to undergo CEA (N = 35); Control cohort patients who refused CEA (N = 11). DSM-IV-Psychiatric diagnosis made by clinicians using interviews, QoL measured by Short Form Health Survey (SF-12); cognitive performance by WAIS Intelligent Coefficient (IC). RESULTS: The study showed a better improvement during six months in Overall IC, Performance IC and Verbal IC in the group that underwent CEA. QoL in the two cohorts did not reach statistical significance. Percentages of patients who improved in the CEA group were significantly higher with regard to Overall and Verbal IC scores, and at the limits of statistical significance in Performance IC. The differences of subject with improvement in SF-12 score in the two groups did not reach statistical significance. Ages below 68 were found to be determinant of a good outcome in Overall IC score. Limit: study conducted with a small sample size. CONCLUSIONS: Patients with severe carotid atherosclerosis who underwent CEA enhanced their cognitive performance.

Cardiac surgery in 260 octogenarians: a case series.

BACKGROUND: The elderly undergo cardiac surgery more and more frequently, often present multiple comorbidities, assume chronic therapies, and present a unique physiology. Aim of our study was to analyze the experience of a referral cardiac surgery center with all types of cardiac surgery interventions performed in patients ≥80 years old over a six years' period. METHODS: A retrospective observational study performed in a university hospital. 260 patients were included in the study (3.5% of the patients undergoing cardiac surgery in the study period). RESULTS: Mean age was 82 ± 1.8 years. Eighty-five percent of patients underwent elective surgery, 15% unplanned surgery and 4.2% redo surgery. Intervention for aortic valve pathology and coronary artery bypass grafting were performed in 51% and 46% of the patients, respectively. Interventions involving the mitral valve were the 26% of the total, those on the tricuspid valve were 13% and those on the ascending aortic arch the 9.6%. Postoperative low output syndrome was identified in 44 patients (17%). Mortality was 3.9% and most of the patients (91%) were discharged from hospital in good clinical conditions. Hospital mortality was lower in planned vs unplanned surgery: 3.8% vs 14% respectively. Chronic obstructive pulmonary disease (OR 9.106, CI 2.275 - 36.450) was the unique independent predictor of mortality. CONCLUSIONS: Clinicians should be aware that cardiac surgery can be safely performed at all ages, that risk stratification is mandatory and that hemodynamic treatment to avoid complications is expected.

Depression and cerebrovascular disease: could vortioxetine represent a valid treatment option?

INTRODUCTION: Depression and cerebrovascular atherosclerosis often occur in comorbidity showing neuropsychological impairment and poor response to antidepressant treatment. Objective is to evaluate if new antidepressant vortioxetine may be a potential treatment option. Mechanism of Action : Vortioxetine has 5-HT3, 5-HT7 and 5-HT1D antagonists, 5-HT1B partial agonist and a 5-HT1A agonist and serotonin transporter inhibitor property. Efficacy and safety in Major Depressive Disorders and in cognitive impairment : The majority of trials (one of them in older people) showed efficacy for vortioxetine against placebo and no differences against other active treatments. The Adverse Effects ranged from 15.8% more to 10.8% less than placebo. In the elderly, only nausea was found higher than placebo. Effects on arterial blood pressure and cardiac parameters including the ECG-QT segment were similar to placebo. Elderly depressive patients on vortioxetine showed improvement versus placebo and other active comparators in Auditory Verbal Learning Test and Digit Symbol Substitution Test scores. The inclusion criteria admitted cases with middle cerebrovascular disease. Conclusion : The mechanism of action, the efficacy on depression and safety profile and early data on cognitive impairment make Vortioxetine a strong candidate for use in depression associated with cerebrovascular disease. This information must be supported by future randomized controlled trials.

Reducing mortality in acute kidney injury patients: systematic review and international web-based survey.

OBJECTIVE: To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting. DESIGN AND SETTING: Systematic literature review and international web-based survey. PARTICIPANTS: More than 300 physicians from 62 countries. INTERVENTIONS: Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality. MEASUREMENTS AND MAIN RESULTS: Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions. CONCLUSION: The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics.

Exploring Outcome Priorities and Real-Life Management of Chemotherapy-Induced Peripheral Neurotoxicity: A Survey of the Italian Association for the Study of Pain members.

Introduction: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and neuropathic pain. The Desirability of Outcome Ranking (DOOR) framework is proposed as a better way to assess preventive or therapeutic interventions for CIPN. Methods: A survey was conducted among Italian healthcare professionals and researchers affiliated to the Italian Chapter of the International Association for the Study of Pain (AISD) to identify the most important outcomes in clinical management and research. Results: Among the 73 respondents, 61 qualified for the survey, with an overall response rate of 1.2%. The vast majority were physicians (77%), most of whom were anesthesiologists (47.5%). The results showed that pain, survival, sensory impairment, motor impairment, and quality of life were consistently ranked as the most important outcomes, but there was significant disagreement in the outcomes relative ranking, making it difficult to develop a DOOR algorithm. The study also revealed that clinicians commonly use structured interviews to evaluate patients with CIPN, and the most prescribed drugs or supplements were palmitoylethanolamide, pregabalin, gabapentin and alpha lipoic acid as preventive agents and pregabalin, palmitoylethanolamide, duloxetine, gabapentin, and amitriptyline as therapeutic agents. However, many of these drugs have not been clinically proven to be effective for CIPN. Discussion: This study suggests that the implementation of a DOOR framework for CIPN using healthcare professionals is more difficult than expected, given the significant disagreement in our respondents' ranking of outcomes. Our work provides interesting topics for future research in CIPN, but its limitations include a small sample size, a low response rate, and a possible selection bias.

Randomized evidence for reduction of perioperative mortality.

OBJECTIVE: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence. DESIGN AND SETTING: A web-based international consensus conference. PARTICIPANTS: More than 1,000 physicians from 77 countries participated in this web-based consensus conference. INTERVENTIONS: Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials. MEASUREMENTS AND MAIN RESULTS: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality. CONCLUSIONS: Future research and health care funding should be directed toward studying and evaluating these interventions.

Metabolomics and Microbiomics: New Potential Strategies in Chronic Pain Syndrome.

Chronic pain affects almost 20% of the European adult population and it significantly reduces patients' quality of life. Chronic pain is considered a multidimensional experience determined by the interaction of several genetic and environmental factors. The effect of specific genetic contributions is often unclear, and the interpretation of the results from studies focused on genetic influences on pain has been complicated by the existence of multiple pain phenotypes. A step forward from genetics could be given by the application of metabolomics and microbiomics tools. Metabolomics is a powerful approach for hypothesis generation in biology, and it aims to analyze low molecular weight compounds, either metabolic intermediates or metabolic end-products, resulting from human or microbial metabolism. Microbiomics is a fast-growing field in which all the microbes are examined together, and as a result, its perturbation may indicate the development of chronic diseases. By applying these methodologies for the study of chronic pain, several differences have been identified. The alteration of the choline-PAF pathway is an intriguing finding recognized by several groups. In our opinion, metabolomics and microbiomics techniques will allow significant progress into the medical field. Patients may benefit from the possibility of being stratified and classified based on their metabolic and microbial profile, which, in the next future, may lead to personalized therapy.

Effect of a Low-Moderate Exercise Program on Dysmetabolism in Older Adults: Results of a Randomized Controlled Trial.

Physical exercise has been shown to improve dysmetabolism in older adults, reducing cardiovascular risk, while its role in preventing dysmetabolism is less known. Moreover, most of the trials use exercise programs that are difficult to put into daily practice. The purpose of this Randomized Controlled Trial (RCT) was to evaluate the effectiveness of a 3-month moderate exercise program in improving or preventing dysmetabolism in 120 older adults, randomly selected for the exercise program (experimental group) or cultural activities (control group). None of the subjects were following a hypocaloric diet, and all of them reported healthy eating habits. Anthropometric (Body Mass Index (BMI) and Waist Circumference (WC)) and metabolic variables (fasting plasma glucose (FPG), High-Density Lipoprotein Cholesterol (HDL-C), and triglycerides (TG)) were assessed at baseline (T0) and at the end of the trial (T1). Dysmetabolism was defined by the presence of an increased WC plus at least two metabolic alterations. At T0, the two groups did not differ by sex, age, education, BMI, WC, FPG, HDL-C levels, and prevalence of dysmetabolism. The mean BMI value indicated overweight, and WC values were higher than the cut-off. At T1, a slight reduction in the number of people with dysmetabolism was found only in the experimental group. However, none of the individuals without dysmetabolism at T0 in the experimental group developed it at T1, while 11.4% developed it in the control group (p = 0.032). This study highlights that a moderate exercise program, accessible in daily practice, can prevent dysmetabolism in older adults, even while being overweight, while if dysmetabolism is already present, more prolonged combined nutritional and exercise interventions will be needed.