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Papers by Annalisa Biffi

Therapeutic Advances in Musculoskeletal Disease

Background: Noncommunicable, chronic diseases need pharmacological interventions for long periods... more Background: Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a ‘medication holiday,’ should be planned by healthcare professionals. Objectives: We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines. Design: Systematic review. Data Sources and Methods: We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. ...

Background The application of non-invasive pelvic circumferential compression devices (PCCDs), in... more Background The application of non-invasive pelvic circumferential compression devices (PCCDs), including pelvic binders, has shown to improve the position and stability of some types of pelvic fractures. To date the clinical efficacy of PCCDs application is still scarce and of poor quality. We assessed the clinical efficacy of pelvic binder pre-hospital in the management of pelvic fracture. Methods We systematically searched MEDLINE (PubMed), EMBASE and Cochrane CENTRAL up to June 2022. Two authors independently extracted data and appraised risk of bias using the Newcastle Ottawa Scale for observational studies. The quality of evidence was assessed using the Grading of Recommendations Assessment (GRADE) approach. Results We included ten studies with a total of 2770 participants. None of the included studies showed a statistically significant difference in overall mortality, 48h or 30-day mortality in PCCD group compared to no PCCD, whereas a reduction of mortality was observed in fa...

Frontiers in Endocrinology, Apr 18, 2023

Hypertension

Background: Whether and to what extent the reported blood pressure (BP) lowering effects of renal... more Background: Whether and to what extent the reported blood pressure (BP) lowering effects of renal denervation (RDN) are associated with a central sympathoinhibition is controversial. We examined this issue by performing a meta-analysis of the microneurographic studies evaluating the BP and muscle sympathetic nerve activity (MSNA) responses to RDN in drug-resistant or uncontrolled hypertension (RHT). Methods: This analysis comprised 11 studies including a total of >400 RHT patients undergoing RDN and were followed up for 6 months. Evaluation was extended to the relationships of MSNA with clinic heart rate and BP changes associated with RDN. Results: MSNA showed a significant reduction after RDN (−4.78 bursts/100 heart beats; P <0.04), which was also accompanied by a significant systolic (−11.45 mm Hg; P <0.002) and diastolic (−5.24 mm Hg; P =0.0001) BP decrease. No significant quantitative relationship was found between MSNA and systolic (r=−0.96, P =0.19) or diastolic BP (r...

World Journal of Emergency Surgery

Background A structured approach involves systematic management of trauma patients. We aim to con... more Background A structured approach involves systematic management of trauma patients. We aim to conduct an overview of reviews about the clinical efficacy and safety of structured approach (i.e., primary and secondary survey) by guideline checklist compared to non-structured approach (i.e. clinical examination); moreover, routine screening whole-body computer tomography (WBCT) was compared to non-routine WBCT in patients with suspected major trauma. Methods We systematically searched MEDLINE (PubMed), EMBASE and Cochrane Database of Systematic Reviews up to 3 May 2022. Systematic reviews (SRs) that investigated the use of a structured approach compared to a non-structured approach were eligible. Two authors independently extracted data, managed the overlapping of primary studies belonging to the included SRs and calculated the corrected covered area (CCA). The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodo...

Additional file 1: Supplement A. Search strategies. Supplement B. Characteristics of included stu... more Additional file 1: Supplement A. Search strategies. Supplement B. Characteristics of included studies. Supplement C. Accuracy data of pre-hospital tools. Supplement D. Net clinical benefit curves. Supplement E. Quality assessment QUADAS 2. Supplement F. Summary of findings tables.

International Journal of Environmental Research and Public Health, 2021

Trauma is one of the leading causes of uncontrolled haemorrhage, death, and disability. Use of a ... more Trauma is one of the leading causes of uncontrolled haemorrhage, death, and disability. Use of a tourniquet can be considered an optimal anti-haemorrhagic resource, in pre-hospital and emergency settings, and its lifesaving effect is clinically contradictory. This review aims to assess the clinical efficacy of the tourniquet in the emergency pre-hospital care setting for the management of haemorrhage. We conducted the systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the PRISMA statement. We searched the following electronic databases: EMBASE, MEDLINE, and Cochrane-CENTRAL. All studies included were appraised for risk of bias. Prevalent primary outcomes were mortality and use of blood products. Secondary outcomes were related to adverse effects. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Four studies were involved (1762 trauma patients). The adjus...

Journal of Trauma and Acute Care Surgery, 2021

BACKGROUND Early detection of critical bleeding by accurate tools can help ensure rapid delivery ... more BACKGROUND Early detection of critical bleeding by accurate tools can help ensure rapid delivery of blood products to improve outcomes in major trauma patients. We conducted a systematic review to evaluate the accuracy of risk tools to predict critical bleeding in patients with major trauma. METHODS PubMed, Embase and CENTRAL were searched up to February 2021 for studies investigating risk tools to predict critical bleeding for major trauma people in pre-hospital and emergency department. We followed the PRISMA-DTA guidelines. Two independent authors included studies, extracted data, appraised the quality using the Quality Assessment of Diagnostic Accuracy Studies-2 and assessed the certainty of evidence using thee Grading of Recommendations Assessment, Development and Evaluation methodology. Sensitivity, specificity and the Receiver Operating Characteristics curve for all selected triage tools. RESULTS Eighty-nine observational studies for adults and 12 observational studies for children met our inclusion criteria. In adults, we found 23 externally validated and 28 un-validated tools; in children, 3 externally validated tools and 5 un-validated. In the externally validated tools, we identified those including clinical, laboratory and ultrasound assessments. Among tools including only a clinical assessment, the Shock Index showed high sensitivity and specificity with the Certainty of Evidence ranging from very low to moderate in adults, as well as Shock Index Pediatric Age-adjusted (SIPA) with a moderate Certainty of Evidence. We found that tools using clinical, laboratory and ultrasound assessments were overall more accurate than those tools without all three components. CONCLUSIONS Clinicians should consider risk tools to predict critical bleeding in a time-sensitive setting like major life threatening trauma. The Shock index and SIPA are easy and handy tools to predict critical bleeding in the pre-hospital setting. In the emergency department, however, many other tools can be utilized which include laboratory and ultrasound assessments, depending on staff experience and resources. LEVEL OF EVIDENCE Systematic review, diagnostic Level III.

World Journal of Emergency Surgery, 2021

Background We conducted a systematic review to evaluate and compare the accuracy of pre-hospital ... more Background We conducted a systematic review to evaluate and compare the accuracy of pre-hospital triage tools for major trauma in the context of the development of the Italian National Institute of Health guidelines on major trauma integrated management. Methods PubMed, Embase, and CENTRAL were searched up to November 2019 for studies investigating pre-hospital triage tools. The ROC (receiver operating characteristics) curve and net clinical benefit for all selected triage tools were performed. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies–2. Certainty of the evidence was judged with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We found 15 observational studies of 13 triage tools for adults and 11 for children. In adults, according to the ROC curve and the net clinical benefit, the most reliable tool was the Northern French Alps Trauma System (TRENAU), adopting injury severity score (IS...

Pharmacological Research, 2021

Because observational studies often use imperfect measurements, results are prone to misclassific... more Because observational studies often use imperfect measurements, results are prone to misclassification errors. We used as a motivating example the possible teratogenic risks of antiemetic agents in pregnancy since a large observational study recently showed that first-trimester exposure to doxylamine-pyridoxine was associated with significantly increased risk of congenital malformations as a whole, as well as central nervous system defects, and previous observational studies did not show such associations. A meta-analysis on this issue was carried out with the aim to illustrate how differential exposure and outcome misclassifications may lead to uncertain conclusions. Methods Medline, searched to October 2019 for full text papers in English. Summary Odds Ratios (ORs) with confidence intervals (CIs) were calculated using random-effect models. Probabilistic sensitivity analyses were performed for evaluating the extension of differential misclassification required to account for the exposure-outcome association. Results Summary ORs were 1.02 (95 % CI, 0.92-1.15), 0.99 (0.82-1.19) and 1.25 (1.08-1.44) for overall congenital, cardiocirculatory, and central nervous system malformations respectively. By assuming exposure and outcome bias factor respectively of 0.95 (i.e., newborns with congenital defects had exposure specificity 5% lower than healthy newborns) and 1.12 (i.e., exposed newborns had outcome sensitivity 12 % higher than unexposed newborns), summary OR of central nervous system defects became 1.13 (95 % CI, 0.99-1.29) and 1.17 (95 % CI, 0.99-1.38). Conclusion Observational investigations and meta-analyses of observational studies need cautious interpretations. Their susceptibility to several, often sneaky, sources of bias should be carefully evaluated.

Journal of Hypertension, 2020

OBJECTIVE The microneurographic technique has shown that sympathetic overactivity may characteriz... more OBJECTIVE The microneurographic technique has shown that sympathetic overactivity may characterize patients with the metabolic syndrome. However, technical and methodological limitations of the studies prevented to draw definite conclusions. The present meta-analysis evaluated 16 microneurographic studies including 650 individuals, 444 metabolic syndrome patients and 206 healthy controls, respectively. The analysis was primarily based on muscle sympathetic nerve traffic (MSNA) quantified by microneurography in metabolic syndrome. METHODS Assessment was extended to the relationships of MSNA with an indirect neuroadrenergic marker, such as heart rate (HR), anthropometric variables, as BMI, waist-hip ratio and metabolic profile. RESULTS Metabolic syndrome individuals displayed MSNA values (means ± SEM) significantly greater than controls (58.6 ± 4.8 versus 41.6 ± 4.1 bursts/100 heart beats, P < 0.01). This result was independent on the concomitant presence of sleep apnea and drug treatment. MSNA was directly and significantly related to clinic SBP (r = 0.91, P < 0.01) but not to BMI (r = 0.17, P = NS), whereas no significant relationship was found between MSNA and metabolic variables included in the definition of metabolic syndrome. No significant correlation was found between MSNA and HR. CONCLUSION These data provide evidence that metabolic syndrome is characterized by a marked increase (about 30%) in MSNA. They also show that among the variables included in metabolic syndrome definition and related to the sympathetic overdrive blood pressure appears to be the most important one, at variance from what described in obesity in which metabolic and anthropometric factors play a major role. Finally in metabolic syndrome HR does not appear to represent a faithful mirror of the occurring sympathetic activation.

JAMA Network Open, 2021

IMPORTANCE Polypharmacy is a major health concern among older adults. While deprescribing may red... more IMPORTANCE Polypharmacy is a major health concern among older adults. While deprescribing may reduce inappropriate medicine use, its effect on clinical end points remains uncertain. OBJECTIVE To assess the clinical implications of discontinuing the use of statins while maintaining other drugs in a cohort of older patients receiving polypharmacy. DESIGN, SETTING, AND PARTICIPANTS This retrospective, population-based cohort study included the 29 047 residents in the Italian Lombardy region aged 65 years or older who were receiving uninterrupted treatment with statins, blood pressure-lowering, antidiabetic, and

European Journal of Clinical Pharmacology, 2017

Purpose This study aims to systematically review studies quantifying the associations between ant... more Purpose This study aims to systematically review studies quantifying the associations between antidepressants (ADs) use and the risk of cardiovascular (CV) outcomes. Methods Medline was searched to October 2015 for full text articles in English. Prospective cohort and case-control studies were admitted if they investigated the relationship between current use of ADs as a whole, tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs), and the onset CV events. Summary relative risks (RRs) with confidence intervals (CIs) were calculated using randomeffects or fixed-effects models. Results A total of 99,367 incident cases of CV outcomes who met inclusion criteria were identified from 22 observational studies. Compared with no users of ADs, use of SSRIs was associated with an increased risk of cerebrovascular disease (RRs, 1.24; 95% CI, 1.15 to 1.34), while the use of TCA was associated with an increased risk of acute heart disease (RRs, 1.29; 95% CI, 1.09 to 1.54). Conclusions The results of this meta-analysis have to be taken with caution because even though an increased risk of cerebrovascular and acute heart disease was observed respectively in SSRIs and TCA users, the estimates are characterized by a high between study heterogeneity. Moreover, it was not possible to distinguish between the effects of ADs and depression itself. Further well-designed studies are required to confirm this association.

Clinical drug investigation, Jan 27, 2018

BACKGROUND AND OBJECTIVE: Conflicting findings from studies evaluating the association between us... more BACKGROUND AND OBJECTIVE: Conflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better adherence to antidepressant therapy may reduce mortality. The cohort included 29,845 individuals aged ≥ 65 years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008-2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012-2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered ≥ 75%) and outcome, by adjusting and stratifying for several covariates. Pati...

World Journal of Emergency Surgery

Background Multiple studies regarding the use of Resuscitative Endovascular Balloon Occlusion of ... more Background Multiple studies regarding the use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in patients with non-compressible torso injuries and uncontrolled haemorrhagic shock were recently published. To date, the clinical evidence of the efficacy of REBOA is still debated. We aimed to conduct a systematic review assessing the clinical efficacy and safety of REBOA in patients with major trauma and uncontrolled haemorrhagic shock. Methods We systematically searched MEDLINE (PubMed), EMBASE and CENTRAL up to June 2020. All randomized controlled trials and observational studies that investigated the use of REBOA compared to resuscitative thoracotomy (RT) with/without REBOA or no-REBOA were eligible. We followed the PRISMA and MOOSE guidelines. Two authors independently extracted data and appraised the risk of bias of included studies. Effect sizes were pooled in a meta-analysis using random-effects models. The quality of evidence was assessed using the Grading o...

Journal of Hypertension

Supplemental Digital Content is available in the text Background: Studies based on microneurograp... more Supplemental Digital Content is available in the text Background: Studies based on microneurographic sympathetic nerve activity (MSNA) recordings have shown that the sympathetic system is overactivated in chronic kidney disease (CKD) patients but the relationship between MSNA and renal function and other risk factors has not been systematically reviewed in this population. Design and measurements: This meta-analysis compares MSNA in cardiovascular complications-free CKD patients (n = 638) and healthy individuals (n = 372) and assesses the relationship of MSNA with the eGFR, age, BMI and hemodynamic variables. Results: In a global analysis, MSNA was higher in CKD patients than in healthy control individuals (P < 0.001). The difference in MSNA between patients and healthy individuals was more marked in end-stage kidney diseases patients than in stage 3A 3B CKD patients (P < 0.001). In an analysis combining patients and healthy individuals, MSNA rose gradually across progressively lower eGFR categories (P < 0.01). In separate meta-regression analyses in CKD patients and in healthy individuals, MSNA associated directly with age (CKD: r = 0.57, P = 0.022; healthy individuals: r = 0.71, P = 0.031) and with the BMI (r = 0.75, P = 0.001 and r = 0.93, P = 0.003). In both groups, MSNA correlated with heart rate (r = 0.77, P = 0.02 and r = 0.66, P = 0.01) but was unrelated to plasma norepinephrine. Conclusion: Independently of comorbidities, MSNA is markedly increased in CKD patients as compared with healthy individuals and it is related to renal function, age, the BMI and heart rate. Sympathetic activation intensifies as CKD progresses toward kidney failure and such an intensification is paralleled by a progressive rise in heart rate but it is not reflected by plasma norepinephrine.

Nerve traffic recordings (muscle sympathetic nerve traffic [MSNA]) have shown that sympathetic ac... more Nerve traffic recordings (muscle sympathetic nerve traffic [MSNA]) have shown that sympathetic activation may occur in obesity. However, the small sample size of the available studies, presence of comorbidities, heterogeneity of the subjects examined represented major weaknesses not allowing to draw definite conclusions. This is the case for the overweight state. The present meta-analysis evaluated 1438 obese or overweight subjects recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in obesity and overweight, excluding as concomitant conditions hypertension, metabolic syndrome, and other comorbidities. Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, as body mass index, waist-to-hip ratio, presence/absence of obstructive sleep apnea, and metabolic profile. Compared with normoweights MSNA was significantly greater in overweight and more in obese individuals (37.0±4.1 versus 43.2±3.5 and 50.4±5.0 burts/100 heartbeats, P<0.01). This was the case even in the absence of obstructive sleep apnea. MSNA was significantly directly related to body mass index and waist-to-hip ratio (r=0.41 and r=0.64, P<0.04 and <0.01, respectively), clinic blood pressure (r=0.68, P<0.01), total cholesterol, LDL (low-density lipoprotein) cholesterol, and triglycerides (r=0.91, r=0.94, and r=0.80, respectively, P<0.01) but unrelated to plasma insulin, glucose, and homeostatic model assessment for insulin resistance. No significant correlation was found between MSNA, heart rate, and norepinephrine. Thus, obesity and overweight are characterized by sympathetic overactivity which mirrors the severity of the clinical condition and reflects metabolic alterations, with the exclusion of glucose/insulin profile. Neither heart rate nor norepinephrine appear to represent faithful markers of the muscle sympathetic overdrive. (Hypertension.

Therapeutic Advances in Musculoskeletal Disease

Background: Noncommunicable, chronic diseases need pharmacological interventions for long periods... more Background: Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a ‘medication holiday,’ should be planned by healthcare professionals. Objectives: We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines. Design: Systematic review. Data Sources and Methods: We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. ...

Background The application of non-invasive pelvic circumferential compression devices (PCCDs), in... more Background The application of non-invasive pelvic circumferential compression devices (PCCDs), including pelvic binders, has shown to improve the position and stability of some types of pelvic fractures. To date the clinical efficacy of PCCDs application is still scarce and of poor quality. We assessed the clinical efficacy of pelvic binder pre-hospital in the management of pelvic fracture. Methods We systematically searched MEDLINE (PubMed), EMBASE and Cochrane CENTRAL up to June 2022. Two authors independently extracted data and appraised risk of bias using the Newcastle Ottawa Scale for observational studies. The quality of evidence was assessed using the Grading of Recommendations Assessment (GRADE) approach. Results We included ten studies with a total of 2770 participants. None of the included studies showed a statistically significant difference in overall mortality, 48h or 30-day mortality in PCCD group compared to no PCCD, whereas a reduction of mortality was observed in fa...

Frontiers in Endocrinology, Apr 18, 2023

Hypertension

Background: Whether and to what extent the reported blood pressure (BP) lowering effects of renal... more Background: Whether and to what extent the reported blood pressure (BP) lowering effects of renal denervation (RDN) are associated with a central sympathoinhibition is controversial. We examined this issue by performing a meta-analysis of the microneurographic studies evaluating the BP and muscle sympathetic nerve activity (MSNA) responses to RDN in drug-resistant or uncontrolled hypertension (RHT). Methods: This analysis comprised 11 studies including a total of >400 RHT patients undergoing RDN and were followed up for 6 months. Evaluation was extended to the relationships of MSNA with clinic heart rate and BP changes associated with RDN. Results: MSNA showed a significant reduction after RDN (−4.78 bursts/100 heart beats; P <0.04), which was also accompanied by a significant systolic (−11.45 mm Hg; P <0.002) and diastolic (−5.24 mm Hg; P =0.0001) BP decrease. No significant quantitative relationship was found between MSNA and systolic (r=−0.96, P =0.19) or diastolic BP (r...

World Journal of Emergency Surgery

Background A structured approach involves systematic management of trauma patients. We aim to con... more Background A structured approach involves systematic management of trauma patients. We aim to conduct an overview of reviews about the clinical efficacy and safety of structured approach (i.e., primary and secondary survey) by guideline checklist compared to non-structured approach (i.e. clinical examination); moreover, routine screening whole-body computer tomography (WBCT) was compared to non-routine WBCT in patients with suspected major trauma. Methods We systematically searched MEDLINE (PubMed), EMBASE and Cochrane Database of Systematic Reviews up to 3 May 2022. Systematic reviews (SRs) that investigated the use of a structured approach compared to a non-structured approach were eligible. Two authors independently extracted data, managed the overlapping of primary studies belonging to the included SRs and calculated the corrected covered area (CCA). The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodo...

Additional file 1: Supplement A. Search strategies. Supplement B. Characteristics of included stu... more Additional file 1: Supplement A. Search strategies. Supplement B. Characteristics of included studies. Supplement C. Accuracy data of pre-hospital tools. Supplement D. Net clinical benefit curves. Supplement E. Quality assessment QUADAS 2. Supplement F. Summary of findings tables.

International Journal of Environmental Research and Public Health, 2021

Trauma is one of the leading causes of uncontrolled haemorrhage, death, and disability. Use of a ... more Trauma is one of the leading causes of uncontrolled haemorrhage, death, and disability. Use of a tourniquet can be considered an optimal anti-haemorrhagic resource, in pre-hospital and emergency settings, and its lifesaving effect is clinically contradictory. This review aims to assess the clinical efficacy of the tourniquet in the emergency pre-hospital care setting for the management of haemorrhage. We conducted the systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the PRISMA statement. We searched the following electronic databases: EMBASE, MEDLINE, and Cochrane-CENTRAL. All studies included were appraised for risk of bias. Prevalent primary outcomes were mortality and use of blood products. Secondary outcomes were related to adverse effects. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Four studies were involved (1762 trauma patients). The adjus...

Journal of Trauma and Acute Care Surgery, 2021

BACKGROUND Early detection of critical bleeding by accurate tools can help ensure rapid delivery ... more BACKGROUND Early detection of critical bleeding by accurate tools can help ensure rapid delivery of blood products to improve outcomes in major trauma patients. We conducted a systematic review to evaluate the accuracy of risk tools to predict critical bleeding in patients with major trauma. METHODS PubMed, Embase and CENTRAL were searched up to February 2021 for studies investigating risk tools to predict critical bleeding for major trauma people in pre-hospital and emergency department. We followed the PRISMA-DTA guidelines. Two independent authors included studies, extracted data, appraised the quality using the Quality Assessment of Diagnostic Accuracy Studies-2 and assessed the certainty of evidence using thee Grading of Recommendations Assessment, Development and Evaluation methodology. Sensitivity, specificity and the Receiver Operating Characteristics curve for all selected triage tools. RESULTS Eighty-nine observational studies for adults and 12 observational studies for children met our inclusion criteria. In adults, we found 23 externally validated and 28 un-validated tools; in children, 3 externally validated tools and 5 un-validated. In the externally validated tools, we identified those including clinical, laboratory and ultrasound assessments. Among tools including only a clinical assessment, the Shock Index showed high sensitivity and specificity with the Certainty of Evidence ranging from very low to moderate in adults, as well as Shock Index Pediatric Age-adjusted (SIPA) with a moderate Certainty of Evidence. We found that tools using clinical, laboratory and ultrasound assessments were overall more accurate than those tools without all three components. CONCLUSIONS Clinicians should consider risk tools to predict critical bleeding in a time-sensitive setting like major life threatening trauma. The Shock index and SIPA are easy and handy tools to predict critical bleeding in the pre-hospital setting. In the emergency department, however, many other tools can be utilized which include laboratory and ultrasound assessments, depending on staff experience and resources. LEVEL OF EVIDENCE Systematic review, diagnostic Level III.

World Journal of Emergency Surgery, 2021

Background We conducted a systematic review to evaluate and compare the accuracy of pre-hospital ... more Background We conducted a systematic review to evaluate and compare the accuracy of pre-hospital triage tools for major trauma in the context of the development of the Italian National Institute of Health guidelines on major trauma integrated management. Methods PubMed, Embase, and CENTRAL were searched up to November 2019 for studies investigating pre-hospital triage tools. The ROC (receiver operating characteristics) curve and net clinical benefit for all selected triage tools were performed. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies–2. Certainty of the evidence was judged with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We found 15 observational studies of 13 triage tools for adults and 11 for children. In adults, according to the ROC curve and the net clinical benefit, the most reliable tool was the Northern French Alps Trauma System (TRENAU), adopting injury severity score (IS...

Pharmacological Research, 2021

Because observational studies often use imperfect measurements, results are prone to misclassific... more Because observational studies often use imperfect measurements, results are prone to misclassification errors. We used as a motivating example the possible teratogenic risks of antiemetic agents in pregnancy since a large observational study recently showed that first-trimester exposure to doxylamine-pyridoxine was associated with significantly increased risk of congenital malformations as a whole, as well as central nervous system defects, and previous observational studies did not show such associations. A meta-analysis on this issue was carried out with the aim to illustrate how differential exposure and outcome misclassifications may lead to uncertain conclusions. Methods Medline, searched to October 2019 for full text papers in English. Summary Odds Ratios (ORs) with confidence intervals (CIs) were calculated using random-effect models. Probabilistic sensitivity analyses were performed for evaluating the extension of differential misclassification required to account for the exposure-outcome association. Results Summary ORs were 1.02 (95 % CI, 0.92-1.15), 0.99 (0.82-1.19) and 1.25 (1.08-1.44) for overall congenital, cardiocirculatory, and central nervous system malformations respectively. By assuming exposure and outcome bias factor respectively of 0.95 (i.e., newborns with congenital defects had exposure specificity 5% lower than healthy newborns) and 1.12 (i.e., exposed newborns had outcome sensitivity 12 % higher than unexposed newborns), summary OR of central nervous system defects became 1.13 (95 % CI, 0.99-1.29) and 1.17 (95 % CI, 0.99-1.38). Conclusion Observational investigations and meta-analyses of observational studies need cautious interpretations. Their susceptibility to several, often sneaky, sources of bias should be carefully evaluated.

Journal of Hypertension, 2020

OBJECTIVE The microneurographic technique has shown that sympathetic overactivity may characteriz... more OBJECTIVE The microneurographic technique has shown that sympathetic overactivity may characterize patients with the metabolic syndrome. However, technical and methodological limitations of the studies prevented to draw definite conclusions. The present meta-analysis evaluated 16 microneurographic studies including 650 individuals, 444 metabolic syndrome patients and 206 healthy controls, respectively. The analysis was primarily based on muscle sympathetic nerve traffic (MSNA) quantified by microneurography in metabolic syndrome. METHODS Assessment was extended to the relationships of MSNA with an indirect neuroadrenergic marker, such as heart rate (HR), anthropometric variables, as BMI, waist-hip ratio and metabolic profile. RESULTS Metabolic syndrome individuals displayed MSNA values (means ± SEM) significantly greater than controls (58.6 ± 4.8 versus 41.6 ± 4.1 bursts/100 heart beats, P < 0.01). This result was independent on the concomitant presence of sleep apnea and drug treatment. MSNA was directly and significantly related to clinic SBP (r = 0.91, P < 0.01) but not to BMI (r = 0.17, P = NS), whereas no significant relationship was found between MSNA and metabolic variables included in the definition of metabolic syndrome. No significant correlation was found between MSNA and HR. CONCLUSION These data provide evidence that metabolic syndrome is characterized by a marked increase (about 30%) in MSNA. They also show that among the variables included in metabolic syndrome definition and related to the sympathetic overdrive blood pressure appears to be the most important one, at variance from what described in obesity in which metabolic and anthropometric factors play a major role. Finally in metabolic syndrome HR does not appear to represent a faithful mirror of the occurring sympathetic activation.

JAMA Network Open, 2021

IMPORTANCE Polypharmacy is a major health concern among older adults. While deprescribing may red... more IMPORTANCE Polypharmacy is a major health concern among older adults. While deprescribing may reduce inappropriate medicine use, its effect on clinical end points remains uncertain. OBJECTIVE To assess the clinical implications of discontinuing the use of statins while maintaining other drugs in a cohort of older patients receiving polypharmacy. DESIGN, SETTING, AND PARTICIPANTS This retrospective, population-based cohort study included the 29 047 residents in the Italian Lombardy region aged 65 years or older who were receiving uninterrupted treatment with statins, blood pressure-lowering, antidiabetic, and

European Journal of Clinical Pharmacology, 2017

Purpose This study aims to systematically review studies quantifying the associations between ant... more Purpose This study aims to systematically review studies quantifying the associations between antidepressants (ADs) use and the risk of cardiovascular (CV) outcomes. Methods Medline was searched to October 2015 for full text articles in English. Prospective cohort and case-control studies were admitted if they investigated the relationship between current use of ADs as a whole, tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs), and the onset CV events. Summary relative risks (RRs) with confidence intervals (CIs) were calculated using randomeffects or fixed-effects models. Results A total of 99,367 incident cases of CV outcomes who met inclusion criteria were identified from 22 observational studies. Compared with no users of ADs, use of SSRIs was associated with an increased risk of cerebrovascular disease (RRs, 1.24; 95% CI, 1.15 to 1.34), while the use of TCA was associated with an increased risk of acute heart disease (RRs, 1.29; 95% CI, 1.09 to 1.54). Conclusions The results of this meta-analysis have to be taken with caution because even though an increased risk of cerebrovascular and acute heart disease was observed respectively in SSRIs and TCA users, the estimates are characterized by a high between study heterogeneity. Moreover, it was not possible to distinguish between the effects of ADs and depression itself. Further well-designed studies are required to confirm this association.

Clinical drug investigation, Jan 27, 2018

BACKGROUND AND OBJECTIVE: Conflicting findings from studies evaluating the association between us... more BACKGROUND AND OBJECTIVE: Conflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better adherence to antidepressant therapy may reduce mortality. The cohort included 29,845 individuals aged ≥ 65 years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008-2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012-2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered ≥ 75%) and outcome, by adjusting and stratifying for several covariates. Pati...

World Journal of Emergency Surgery

Background Multiple studies regarding the use of Resuscitative Endovascular Balloon Occlusion of ... more Background Multiple studies regarding the use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in patients with non-compressible torso injuries and uncontrolled haemorrhagic shock were recently published. To date, the clinical evidence of the efficacy of REBOA is still debated. We aimed to conduct a systematic review assessing the clinical efficacy and safety of REBOA in patients with major trauma and uncontrolled haemorrhagic shock. Methods We systematically searched MEDLINE (PubMed), EMBASE and CENTRAL up to June 2020. All randomized controlled trials and observational studies that investigated the use of REBOA compared to resuscitative thoracotomy (RT) with/without REBOA or no-REBOA were eligible. We followed the PRISMA and MOOSE guidelines. Two authors independently extracted data and appraised the risk of bias of included studies. Effect sizes were pooled in a meta-analysis using random-effects models. The quality of evidence was assessed using the Grading o...

Journal of Hypertension

Supplemental Digital Content is available in the text Background: Studies based on microneurograp... more Supplemental Digital Content is available in the text Background: Studies based on microneurographic sympathetic nerve activity (MSNA) recordings have shown that the sympathetic system is overactivated in chronic kidney disease (CKD) patients but the relationship between MSNA and renal function and other risk factors has not been systematically reviewed in this population. Design and measurements: This meta-analysis compares MSNA in cardiovascular complications-free CKD patients (n = 638) and healthy individuals (n = 372) and assesses the relationship of MSNA with the eGFR, age, BMI and hemodynamic variables. Results: In a global analysis, MSNA was higher in CKD patients than in healthy control individuals (P < 0.001). The difference in MSNA between patients and healthy individuals was more marked in end-stage kidney diseases patients than in stage 3A 3B CKD patients (P < 0.001). In an analysis combining patients and healthy individuals, MSNA rose gradually across progressively lower eGFR categories (P < 0.01). In separate meta-regression analyses in CKD patients and in healthy individuals, MSNA associated directly with age (CKD: r = 0.57, P = 0.022; healthy individuals: r = 0.71, P = 0.031) and with the BMI (r = 0.75, P = 0.001 and r = 0.93, P = 0.003). In both groups, MSNA correlated with heart rate (r = 0.77, P = 0.02 and r = 0.66, P = 0.01) but was unrelated to plasma norepinephrine. Conclusion: Independently of comorbidities, MSNA is markedly increased in CKD patients as compared with healthy individuals and it is related to renal function, age, the BMI and heart rate. Sympathetic activation intensifies as CKD progresses toward kidney failure and such an intensification is paralleled by a progressive rise in heart rate but it is not reflected by plasma norepinephrine.

Nerve traffic recordings (muscle sympathetic nerve traffic [MSNA]) have shown that sympathetic ac... more Nerve traffic recordings (muscle sympathetic nerve traffic [MSNA]) have shown that sympathetic activation may occur in obesity. However, the small sample size of the available studies, presence of comorbidities, heterogeneity of the subjects examined represented major weaknesses not allowing to draw definite conclusions. This is the case for the overweight state. The present meta-analysis evaluated 1438 obese or overweight subjects recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in obesity and overweight, excluding as concomitant conditions hypertension, metabolic syndrome, and other comorbidities. Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, as body mass index, waist-to-hip ratio, presence/absence of obstructive sleep apnea, and metabolic profile. Compared with normoweights MSNA was significantly greater in overweight and more in obese individuals (37.0±4.1 versus 43.2±3.5 and 50.4±5.0 burts/100 heartbeats, P<0.01). This was the case even in the absence of obstructive sleep apnea. MSNA was significantly directly related to body mass index and waist-to-hip ratio (r=0.41 and r=0.64, P<0.04 and <0.01, respectively), clinic blood pressure (r=0.68, P<0.01), total cholesterol, LDL (low-density lipoprotein) cholesterol, and triglycerides (r=0.91, r=0.94, and r=0.80, respectively, P<0.01) but unrelated to plasma insulin, glucose, and homeostatic model assessment for insulin resistance. No significant correlation was found between MSNA, heart rate, and norepinephrine. Thus, obesity and overweight are characterized by sympathetic overactivity which mirrors the severity of the clinical condition and reflects metabolic alterations, with the exclusion of glucose/insulin profile. Neither heart rate nor norepinephrine appear to represent faithful markers of the muscle sympathetic overdrive. (Hypertension.