The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice.

Novel coronavirus 2019 is a single-stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019. Clinical data from the Chinese outbreak have been reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the coronavirus disease 2019 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including: safe oxygen therapy; airway management; personal protective equipment; and non-technical aspects of caring for patients diagnosed with coronavirus disease 2019. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.

Cultures of a human synovial cell line to evaluate platelet-rich plasma and hyaluronic acid effects.

Synovial inflammation plays an important role in osteoarthritis (OA) pathogenesis. Different biological compounds have been tested mainly on chondrocytes, to treat early stages of OA. However, because OA has been recently defined as "an organ" pathology, investigation on synoviocytes is also needed. Therefore, the aim of the present study was to validate a human fibroblast-like synoviocytes cell line (K4IM) to test the effects of platelet-rich plasma (PRP) and hyaluronan (HA) on anabolic and catabolic gene expression and on HA secretion from cell cultures. In order to determine the effect of PRP and HA, K4IM cells were maintained in culture with or without TNF-α stimulation. In the presence of PRP, unstimulated K4IM cells presented the same expression of IL1B, IL6, CXCL8, VEGF, TIMP1, and hyaluronic synthase isoform HAS3 as primary human synoviocytes, while HA addition did not change their expression pattern, which was similar to control cells. Stimulated cells expressed significantly higher values of IL1B, CXCL8, and VEGF compared with unstimulated ones. PRP did not show any modification, except for VEGF, while HA addition modulated IL1B expression. PRP did not modulate HA release of both stimulated and unstimulated cells. Our study showed the possibility to use K4IM synoviocytes as an in vitro model to test biological compounds useful for the treatment of early OA. Primary cells reflect the phenotype of cells in vivo, but limited recovery from biopsies and restricted lifespan makes experimental manipulation challenging. Therefore, despite cell lines present some limitations, they could be used as an alternative for preliminary experiments.

Patients control preferences and results in knee arthroplasty.

PURPOSE: Patient engagement in a patient-physician decision-making process has been correlated with satisfaction and clinical outcomes. Aim of this study is to evaluate if patient control preference may also influence TKA results. METHODS: One hundred and seventy-six patients (120w-56m, age 66 ± 9 years, BMI 28 ± 4) underwent TKA and were prospectively evaluated, before surgery and at 6 and 12 months. The preoperative assessment included the Control Preference Scale (CPS) and other scales measuring psychological aspects (STAI, BDI, TSK), as well as SF12 (physical and mental subscales) and the assessment of pain and function. Pain, function, and SF12 subscales were then used to evaluate the improvement at 6- and 12-month follow-up. RESULTS: Pain, function, and SF12 scores improved at 6 and 12 months. CPS correlated with the outcome: pain and functional improvement at 6 months (p = 0.014; p = 0.003, respectively), patient function at 6 months (p = 0.022), improvement of SF12 physical subscale at 6 and 12 months (p = 0.027; p = 0.037, respectively), and satisfaction at 6 months (p = 0.033). Moreover, the multivariate analysis confirmed the importance of CPS regardless of other demographic, physical or psychological characteristics. CONCLUSION: In contrast with previous literature findings, this study shows that patients with more propensity for control presented lower improvements of pain and function than those more prone to rely on the physician making the decision. Physicians should be aware that the patient control preference may influence the treatment outcome and undertake measurements to optimize patient participation in the shared process to optimize the chances of TKA success. LEVEL OF EVIDENCE: IV.

Kinesiophobia and depression affect total knee arthroplasty outcome in a multivariate analysis of psychological and physical factors on 200 patients.

PURPOSE: To evaluate the effects of kinesiophobia on the outcomes of total knee arthroplasty (TKA), and to investigate whether kinesiophobia represents an independent factor influencing the surgery success or whether the observed effects are driven by other physical or psychological aspects such as anxiety and depression. METHODS: Two hundred patients were evaluated prospectively (mean age 65.7 ± 9.1 years, 134 women and 66 men) at 12 months after TKA. Kinesiophobia was assessed with the Tampa Scale for kinesiophobia (TSK: Activity Avoidance-TSK1 and Harm-TSK2 subscales); anxiety and depression were assessed with STAI and BDI, respectively, and preoperative pain and function, sex, age, BMI, education level, number of painful joints and years of symptoms' duration before surgery were documented as well. Results were evaluated with pain and function on 0-10 numeric rating scales, while the overall clinical outcome was documented with WOMAC and SF-12 (Physical and Mental subscales) scores. RESULTS: TSK1 was correlated with WOMAC results at 12 months (p = 0.005, ρ = 0.197). STAI (p = 0.002, ρ = 0.222), BDI (p < 0.0005, ρ = 0.307), and sex (p = 0.004) also influenced the outcome after TKA, while other parameters, such as age, BMI, education level, and number of painful joints and years of symptoms' duration before surgery, did not correlate with the clinical outcome. The multivariate analysis confirmed the role of BDI (p = 0.006, partial η 2 = 0.038), TSK1 (p = 0.011, partial η 2 = 0.033), and sex (p = 0.048, partial η 2 = 0.020), and a synergic interaction of BDI and TSK1, which together presented an even stronger correlation (p < 0.0005, partial η 2 = 0.111) with WOMAC at 12-month follow-up. CONCLUSIONS: Kinesiophobia is a factor influencing the outcome after TKA independently from other psychological and physical variables. This risk factor may affect TKA results, especially in women, and shows a further synergic interaction with depression in terms of lower surgical outcome. These findings are of clinical relevance because they show the impact of psychological factors such as kinesiophobia, and suggest the possibility of adopting co-interventions to overcome the fear of physical activity, and in the end improve patient recovery and final outcome after TKA. LEVEL OF EVIDENCE: IV.

Patient kinesiophobia affects both recovery time and final outcome after total knee arthroplasty.

PURPOSE: To evaluate the effects of kinesiophobia on both phases immediately after surgery and the final results after total knee arthroplasty (TKA). METHODS: This study evaluated prospectively 101 patients (mean age 66 ± 8.0 years, 70 women and 31 men), 5 days after surgery, at 1, 6, 12 months, and at a mean final follow-up of 3.2 ± 0.7 years (2.0-4.2 years). Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK: Activity Avoidance-TSK1 and Harm-TSK2 subscales), and results were evaluated with range of motion, pain and function on 0-10 numeric rating scales, WOMAC and SF-12 (Physical and Mental subscales) scores. RESULTS: TSK1 was correlated with the acute postoperative pain measured at 5 days (p = 0.031), pain measured at 12 months (p = 0.018), patient perceived function at 12 months (p = 0.025), SF-12P at 6 months (p < 0.001), SF-12P and SF-12M at 12 months (p = 0.001 and p = 0.005, respectively), and WOMAC at both 6 and 12 months of follow-up (p = 0.005 and p = 0.001). The effect of TSK 1 on the final WOMAC score was significant when corrected by age and sex (p = 0.049, η 2 = 0.041): the youngest female patients were affected even by moderate kinesiophobia levels. CONCLUSIONS: Fear of pain and even more avoidance of movement are strongly correlated both with the acute postoperative pain perception and recovery after surgery up to 1 year, thus presenting a relevant clinical impact on the outcome after TKA. Moreover, this study showed that even though at longer follow-up its impact decreases, patients with higher levels of kinesiophobia may present a poorer final outcome, especially women. LEVEL OF EVIDENCE: IV.

Maxillofacial trauma in the emergency department: pearls and pitfalls in airway management.

Maxillofacial trauma poses a challenge for the anesthesiologist because injuries can often compromise the patient's airways. Airway maintenance is the first step in the American College of Surgeons Advance Trauma Life Support (ATLS®) protocol. However, clinical dilemmas may arise about the best way to manage a potentially life-threatening injury. There are no recommendations about the best time to intubate, the warning signs for deciding to intubate, or which device should be used when difficulty is expected. In this context the ATLS® approach is important but not sufficient. It is also necessary to recognize and be able to manage specific problems in this scenario where clinical priorities may be conflicting, may suddenly change or may be hidden. This clinical review discusses the complexity of this scenario, providing an overview of the conditions at greatest risk for airway obstruction and the options for airway management, on the basis of the recent literature. Clinicians must recognize the milestones and pitfalls of this topic in order to adopt a systematic approach for airway management, to identify specific characteristics associated with it, and to establish the utility of different instruments for airway management.

D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized patients: a subanalysis of the randomized controlled MAGELLAN trial.

BACKGROUND: D-dimer concentrations have not been evaluated extensively as a predictor of increased venous thromboembolism (VTE) risk in acutely ill, hospitalized medical patients. OBJECTIVES: To analyze the relationships between D-dimer concentration, VTE and bleeding in the MAGELLAN trial (NCT00571649). PATIENTS/METHODS: This was a multicenter, randomized, controlled trial. Patients aged ≥ 40 years, hospitalized for acute medical illnesses with risk factors for VTE received subcutaneous enoxaparin 40 mg once daily for 10 ± 4 days then placebo up to day 35, or oral rivaroxaban 10 mg once daily for 35 ± 4 days. Patients (n = 7581) were grouped by baseline D-dimer ≤ 2 × or > 2 × the upper limit of normal. VTE and major plus non-major clinically relevant bleeding were recorded at day 10, day 35, and between days 11 and 35. RESULTS: The frequency of VTE was 3.5-fold greater in patients with high D-dimer concentrations. Multivariate analysis showed that D-dimer was an independent predictor of the risk of VTE (odds ratio 2.29 [95% confidence interval 1.75-2.98]), and had a similar association to established risk factors for VTE, for example cancer and advanced age. In the high D-dimer group, rivaroxaban was non-inferior to enoxaparin at day 10 and, unlike the low D-dimer group, superior to placebo at day 35 (P < 0.001) and days 11-35 (P < 0.001). In both groups, bleeding outcomes favored enoxaparin/placebo. CONCLUSIONS: Elevated baseline D-dimer concentrations may identify acutely ill, hospitalized medical patients at high risk of VTE for whom extended anticoagulant prophylaxis may provide greater benefit than for those with low D-dimer concentrations.

Implications of new anticoagulants in primary practice.

BACKGROUND: Effective prophylaxis and treatment of thromboembolic disorders remain suboptimal in many healthcare systems, partly owing to limitations of traditional anticoagulants. New oral anticoagulants have been developed and among these, rivaroxaban, apixaban and dabigatran etexilate are in the most advanced stage of clinical development. METHOD: A literature search using the PubMed and ClinicalTrials.gov databases was performed to identify English-language publications. The search was performed up to 31 December 2011 with the terms rivaroxaban OR Xarelto, apixaban OR Eliquis and dabigatran OR Pradaxa. Ongoing, completed and published phase III randomised controlled trials were selected as the primary source of information for the clinical development programme of each drug. RESULTS: The new oral agents demonstrate several advantages over traditional anticoagulants, including administration at fixed doses and no requirement for routine coagulation monitoring On the basis of phase III clinical trials, rivaroxaban, apixaban and dabigatran etexilate have been approved in many countries for the prevention of venous thromboembolism after hip and knee replacement surgery. Dabigatran etexilate and rivaroxaban have also been approved for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in Europe and the US. In addition, rivaroxaban has been approved in Europe for the treatment of acute deep vein thrombosis and prevention of recurrent venous thromboembolism. Approval of these agents and postapproval monitoring of their safety and efficacy will have implications for primary care. CONCLUSION: Rivaroxaban, apixaban and dabigatran etexilate offer the possibility of simplified prevention and treatment strategies for thromboembolic disorders in the outpatient setting.

Real-world practices to prevent venous thromboembolism with pharmacological prophylaxis in US orthopedic surgery patients: an analysis of an integrated healthcare database.

Major orthopedic surgery patients are at high risk of venous thromboembolism (VTE) in-hospital and post-discharge. This study assessed real-world inpatient and outpatient thromboprophylaxis practices following knee or hip arthroplasty. Patients from the Henry Ford Health System aged ≥18 years undergoing knee and hip arthroplasty (January 1997-June 2007) were identified using Current Procedural Terminology codes from administrative databases. Patients with <18 months of continuous enrollment in the system's health maintenance organization or with a current diagnosis of atrial fibrillation were excluded. Both inpatient and outpatient pharmacological prophylaxis was assessed. The analysis included 1393 (58.5%) patients following knee arthroplasty and 989 (41.5%) following hip arthroplasty. Average length of hospitalization was 4.9 days over the study period, although the median stay decreased from 5 days in 1997 to 3 days in 2007. Of patients included, 72.7% received pharmacological prophylaxis only in the inpatient setting following knee arthroplasty and 73.9% following hip arthroplasty. Both inpatient and outpatient pharmacological prophylaxis was received by 12.5% of knee and 12.3% of hip arthroplasty patients. Total length of pharmacological prophylaxis fluctuated between 2 to 4 days between 1997 and 2005, but increased to 11.5 ± 9.0 days in 2007. Although the duration of prophylaxis has recently increased, considerable numbers of hip and knee arthroplasty patients only receive prophylaxis for part of the time period recommended by guidelines. Further efforts are required to ensure the recommended duration of thromboprophylaxis is prescribed to all patients and continued outpatient VTE prophylaxis is provided.

Hospital-based costs associated with venous thromboembolism treatment regimens.

INTRODUCTION: Venous thromboembolism (VTE) poses a significant health and economic burden in US hospitals. Clinical guidelines for acute VTE treatment recommend antithrombotic therapy (at least 5 days) with low molecular weight heparin (LMWH) or unfractionated heparin (UFH). With upcoming US national performance measures requiring successful implementation of evidence-based therapy, cost considerations for anticoagulant choice are of increasing importance to hospitals. METHODS: This retrospective cohort analysis utilizes discharge records from a large real-world US population (January 2002 to December 2006) to provide total, direct, inpatient medical costs associated with LMWH and UFH for acute VTE treatment. Furthermore, for both LMWH and UFH discharges, we compare VTE-related readmission rates at 30 and 90 days after discharge. RESULTS: In total, 57 131 discharges were identified (57.7% LMWH; 42.3% UFH). After adjustment for covariates, including age, severity of illness, and length of stay, total direct medical costs per hospital discharge for UFH were $3476.22 vs. $3056.42 for LMWH (P < 0.0001; difference $420). Costs were significantly higher in the UFH group for most cost categories. Notably, drug acquisition cost was higher for LMWH. LMWH treatment was 12% [odds ratio (OR) 0.876; P < 0.001] and 10% (OR 0.895; P = 0.0006) less likely to result in VTE readmission within 30 and 90 days, respectively. CONCLUSIONS: This study provides the first large, real-world analysis of the total direct medical costs of treating VTE in-hospital. It confirms that, despite higher drug acquisition costs, LMWH is cost-saving compared with UFH in the inpatient setting, and is associated with a lower VTE readmission rate at 30 and 90 days than is UFH.

Applying scientific criteria to therapeutic interchange: a balanced analysis of low-molecular-weight heparins.

Under pressure to provide cost-effective healthcare, many healthcare systems have adopted Therapeutic Interchange (TI) programs-the interchange of therapeutically equivalent but chemically unique drugs-to reduce the total cost of therapy without compromising patient care. To be appropriate and feasible, a TI program for any class of drugs must meet certain rigorous criteria and undergo medical, financial, tactical, and legal reviews. Moreover, once a TI program is implemented, a process to monitor its success should be established. Application of the TI criteria to low-molecular-weight heparins (LMWHs) reveals that a blanket TI program for LMWHs does not appear advisable at this time.