Opportunities for an early recognition of spinal muscular atrophy in primary care: a nationwide, population-based, study in Italy.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of severity. Although an early diagnosis of SMA is crucial to allow proper management of patients, the diagnostic delay is still an issue. Therefore, this study aimed to investigate the clinical correlates of SMA among primary care patients. METHODS: The Health Search Database (HSD) was adopted. To estimate the prevalence and incidence rate of SMA, a cohort study was conducted on the population (aged ≥6 years) being registered in HSD from 1 January 2000 up to 31 December 2019. To investigate the clinical correlates of SMA, a nested case-control study was performed. SMA cases have been classified according to a clinically based iterative process as "certain", "probable" or "possible". To test the association between clinical correlates and SMA cases a multivariate conditional logistic regression model was estimated. RESULTS: The SMA prevalence combining "certain", "probable" and "possible" cases was 5.1 per 100,000 in 2019 (i.e. 1.12 per 100,000 when limited to "certain" cases), while the yearly incidence rate ranged from 0.12 to 0.56 cases per 100,000. Comparing "certain" cases with matched controls, the presence of neurology visits (OR = 6.5; 95% CI: 1.6-25.6) and prescription of electromyography (OR = 4.6; 95% CI: 1.1-18.7) were associated with higher odds of SMA diagnosis. CONCLUSIONS: Our findings suggest that primary care databases may be used to enhance the early identification of SMA. Additional efforts are needed to exploit the electronic health records of general practitioners to allow early recognition of SMA.

Development and internal validation of a prognostic model for 15-year risk of Alzheimer dementia in primary care patients.

BACKGROUND: The exploitation of routinely collected clinical health information is warranted to optimize the case detection and diagnostic workout of Alzheimer's disease (AD). We aimed to derive an AD prediction score based on routinely collected primary care data. METHODS: We built a cohort selecting 199,978 primary care patients 60 + part of the Health Search Database between January 2002 and 2009, followed up until 2019 to detect incident AD cases. The cohort was randomly divided into a derivation and validation sub-cohort. To identify AD and non-AD cases, we applied a clinical algorithm that involved two clinicians. According to a nested case-control design, AD cases were matched with up to 10 controls based on age, sex, calendar period, and follow-up duration. Using the derivation sub-cohort, 32 potential AD predictors (sociodemographic, clinical, drug-related, etc.) were tested in a logistic regression and selected to build a prediction model. The predictive performance of this model was tested on the validation sub-cohort by mean of explained variation, calibration, and discrimination measurements. RESULTS: We identified 3223 AD cases. The presence of memory disorders, hallucinations, anxiety, and depression and the use of NSAIDs were associated with future AD. The combination of the predictors allowed the production of a predictive score that showed an explained variation (pseudo-R2) for AD occurrence of 13.4%, good calibration parameters, and an area under the curve of 0.73 (95% CI: 0.71-0.75). In accordance with this model, 7% of patients presented with a high-risk score for developing AD over 15 years. CONCLUSION: An automated risk score for AD based on routinely collected clinical data is a promising tool for the early case detection and timely management of patients by the general practitioners.

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.

Dexmedetomidine reduces the risk of delirium, agitation and confusion in critically Ill patients: a meta-analysis of randomized controlled trials.

OBJECTIVES: Delirium frequently is observed in critically ill patients in the intensive care unit (ICU) and is associated strongly with a poor outcome. Dexmedetomidine seems to reduce time to extubation and ICU stay without detrimental effects on mortality. The objective of the authors' study was to evaluate the effect of this drug on delirium, agitation, and confusion in the ICU setting. DESIGN: Meta-analysis of all the randomized clinical trials ever performed on dexmedetomidine versus any comparator in the ICU setting. SETTING: Intensive care units. PARTICIPANTS: Critically ill patients. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials. Primary endpoint was the rate of delirium, including the adverse events, agitation and confusion. The 13 included manuscripts (14 trials) randomized 3,029 patients. Overall analysis showed that the use of dexmedetomidine was associated with significant reductions in the incidence of delirium, agitation and confusion (298/1,565 [19%] in the dexmedetomidine group v 337/1,464 [23%] in the control group, RR = 0.68 [0.49 to 0.96], p = 0.03). Results were confirmed in subanalyses performed on patients undergoing noninvasive ventilation (1/53 [2%] in the dexmedetomidine group v 7/49 [14%] in the control group, RR=0.18 [0.03 to 1.01], p = 0.05), receiving midazolam as a comparator (268/1,164 [23%] in the dexmedetomidine group v 277/1,025 [27%] in the control group, RR = 0.68 [0.47 to 1.00], p = 0.05) and in general ICU setting patients (204/688 [30%] in the dexmedetomidine group v 204/560 [36%] in the control group, RR = 0.68 [0.45 to 0.81], p < 0.01). CONCLUSIONS: This meta-analysis of randomized controlled studies suggests that dexmedetomidine could help to reduce delirium in critically ill patients.

Treating depression in clinical practice: new insights on the multidisciplinary use of trazodone.

Depression is estimated to be a leading contributor to the global mental health-related burden. The determinants of this huge prevalence lie in the fact that depressive symptoms may be comorbid in a wide variety of disorders, thus complicating and exacerbating their clinical framework. This makes the treatment of depressive symptoms difficult, since many pharmacological interactions should be considered by physicians planning therapy. Hence, depression still represents a challenge for both psychiatrists and other clinicians, in terms of its high rates of relapse and resistance despite well-established protocols. It is also complicated by the well-known latency in its complete response to current antidepressant treatments. In this context, the search for new strategies regarding antidepressant treatment is mandatory. Revising the use of "old" pharmacotherapies by considering their specific features may help to perfecting the treatment of depression, both in its standalone psychiatric manifestation and in the framework of other clinical conditions. Using a nominal group technique approach, the results of a consensus of expert physicians regarding the possible use of trazodone as a valuable strategy for addressing the "real world" unmet needs of depression treatment in different fields (psychiatry, primary care, neurology and geriatrics) is herein provided. This idea is based on the unique characteristics of this drug which delivers a more rapid antidepressant action as compared to other selective serotonin reuptake inhibitors. It also has pharmacodynamic malleability (i.e., the possibility of exerting different effects on depressive symptoms at different dosages) and pharmacokinetic tolerability (i.e., the possibility of being used as an add-on to other antidepressants with scarce interaction and achieving complimentary effects) when used in the milieu of other drugs in treating comorbid depressive symptoms. Moreover, the large number of formulations available permits finite dosage adjustments, and the use of trazodone for specific pathologies, such as dysphagia. Therefore, although additional studies exploring the real-world conditions of antidepressant treatment are warranted, experts agree on the idea that depressive disorder, in both its standalone and its comorbid manifestations, may surely take advantage of the particular characteristics of trazodone, thus attempting to reach the greatest effectiveness in different contexts.

Dementia and comorbidities in primary care: a scoping review.

BACKGROUND: People with dementia (PwD) are known to have more chronic conditions compared to those without dementia, which can impact the clinical presentation of dementia, complicate clinical management and reduce overall quality of life. While primary care providers (PCPs) are integral to dementia care, it is currently unclear how PCPs adapt dementia care practices to account for comorbidities. This scoping review maps recent literature that describes the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities, identifies critical knowledge gaps and proposes potential avenues for future research. METHODS: We searched for peer-reviewed literature published between 2017-2022 in MEDLINE, Cochrane Library, and Scopus using key terms related to dementia, primary care, and comorbidity. The literature was screened for relevance by title-abstract screening and subsequent full-text screening. The prioritized papers were categorized as either 'Risk Assessment and Prevention', 'Screening, Detection, and Diagnosis' or 'Management' and were further labelled as either 'Tools and Technologies', 'Recommendations for Clinical Practice' or 'Programs and Initiatives'. RESULTS: We identified 1,058 unique records in our search and respectively excluded 800 and 230 publications during title-abstract and full-text screening. Twenty-eight articles were included in our review, where ~ 50% describe the development and testing of tools and technologies that use pre-existing conditions to assess dementia risk. Only one publication provides official dementia screening guidelines for PCPs in people with pre-existing conditions. About 30% of the articles discuss managing the care of PwD, where most were anchored around models of multidisciplinary care and mitigating potentially inappropriate prescribing. CONCLUSION: To our knowledge, this is the first scoping review that examines the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities. Given our findings, we recommend that future studies: 1) further validate tools for risk assessment, timely detection and diagnosis that incorporate other health conditions; 2) provide additional guidance into how comorbidities could impact dementia care (including prescribing medication) in primary care settings; 3) incorporate comorbidities into primary care quality indicators for dementia; and 4) explore how to best incorporate dementia and comorbidities into models/frameworks of holistic, person-centred care.

Protein C zymogen in severe sepsis: a double-blinded, placebo-controlled, randomized study.

PURPOSE: To determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock. METHODS: This is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90 days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90 days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality. RESULTS: The study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79 % (15 patients) in the protein C zymogen group and 67 % (12 patients) in the placebo group (p = 0.40) and for a concomitant safety issue: ICU mortality was 79 % (15 patients) in the protein C zymogen group vs 39 % (7 patients) in the placebo group (p = 0.020), and 30-day mortality was 68 vs 39 % (p = 0.072). CONCLUSION: Protein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.

Clinical aspects of sepsis: an overview.

Sepsis is one of the oldest and most elusive syndromes in medicine. With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was considered as a systemic infection by a pathogenic organism. Although the germ is probably the beginning of the syndrome and one of the major enemies to be identified and fought, sepsis is something wider and more elusive. In this chapter clinically relevant themes of sepsis will be approached to provide an insight of everyday clinical practice for healthcare workers often not directly involved in the patient's management.

Beneficial impact of levosimendan in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials.

INTRODUCTION: The incidence of Acute Kidney Injury is nowadays high in critically ill patients. Its etiology is multifactorial and a primary role is played by low cardiac output syndrome. Everything targeted to normalize cardiac output should increase the renal perfusion and abolish the secondary vasoconstriction. Levosimendan is a calcium sensitizer drug with inotropic properties that improves cardiac output and seems to increase renal blood flow. The aim of this meta-analysis was to evaluate the role of levosimendan in critically ill patients with or at risk of Acute Kidney Injury. METHODS: We performed a meta-analysis of  randomized controlled trials searching for trials that compared levosimendan with any comparator. The endpoints were the number of patients receiving Renal Replacement Therapy after randomization and the number of patients developing Acute Kidney Injury. RESULTS: Final analysis included 33 trials and 3,879 patients (2,024 levosimendan and 1,855 control). The overall analysis showed that the use of levosimendan was associated with a significant reduction in the risk of Renal Replacement Therapy (17 of 492 [3.5%] in the levosimendan group versus 37 of 427 [8.7%] in the control group, relative risk =0.52 [0.32 to 0.86], p for effect =0.01) and of Acute Kidney Injury (114 of 1,598 [7.1%] in the levosimendan group versus 143 of 1,529 [9.4%] in the control arm, relative risk =0.79 [0.63 to 0.99], p for effect =0.048). CONCLUSIONS: This meta-analysis suggests that the use of levosimendan is associated with a significant reduction of Renal Replacement Therapy in critically ill patients.

Beneficial impact of levosimendanin critically ill patients with or at riskfor acute renal failure: a meta-analysisof randomized clinical trials

The incidence of Acute Kidney Injury is nowadays high in critically ill patients. Its etiology ismultifactorial and a primary role is played by low cardiac output syndrome. Everything targeted to normalizecardiac output should increase the renal perfusion and abolish the secondary vasoconstriction. Levosimendanis a calcium sensitizer drug with inotropic properties that improves cardiac output and seems to increase renalblood flow. The aim of this meta-analysis was to evaluate the role of levosimendan in critically ill patients withor at risk of Acute Kidney Injury.Methods: We performed a meta-analysis of randomized controlled trials searching for trials that comparedlevosimendan with any comparator. The endpoints were the number of patients receiving Renal ReplacementTherapy after randomization and the number of patients developing Acute Kidney Injury.Results: Final analysis included 33 trials and 3,879 patients (2,024 levosimendan and 1,855 control). Theoverall analysis showed that the use of levosimendan was associated with a significant reduction in the riskof Renal Replacement Therapy (17 of 492 [3.5%] in the levosimendan group versus 37 of 427 [8.7%] in thecontrol group, relative risk =0.52 [0.32 to 0.86], p for effect =0.01) and of Acute Kidney Injury (114 of 1,598[7.1%] in the levosimendan group versus 143 of 1,529 [9.4%] in the control arm, relative risk =0.79 [0.63 to0.99], p for effect =0.048).Conclusions: This meta-analysis suggests that the use of levosimendan is associated with a significant reductionof Renal Replacement Therapy in critically ill patients.