Prosthetic valve dysfunction in patients with mechanical heart valves: Results from the Emergency Salam Centre cohort.

INTRODUCTION: Mechanical heart valve (MHV) replacement requires long-life anticoagulation due to the risk of Prosthetic Valve Dysfunction (PVD) and cardioembolism. METHODS: We report data from a prospective observational study conducted on MHV patients in the Khartoum Salam Centre for Cardiac Surgery built by 'Emergency,' an Italian Non-Governmental Organization, to evaluate the occurrence of PVD and associated risk factors. RESULTS: We prospectively followed 3647 patients, and 38 patients (rate 1.04 × 100 pt-years) had PVD during follow-up. The time in therapeutic range (TTR) among patients without PVD was 53 % (IQR 37-67), and it was 43 % (IQR 19-58) among patients with PVD (p = 0.04). Twenty-three over 38 patients (60.5 %) were symptomatic, 18 (47.4 %) had obstructive valvular stenosis, 24 patients (63.2 %) had INR <2.0 at diagnosis, and 21 patients (55.3 %) had been off warfarin for a long time: 3 patients for 1 week, 1 patient for 2 weeks, and 17 patients for >4 weeks (6 patients were off warfarin from 3 to 12 months). Ten were uncompliant to treatment, and 8 were pregnant women. Ten patients (26.3 %) with PVD had had a previous episode of PVD, and 14 patients (36.8 %) had 2 or more associated risk factors. Only in 6 cases were no associate risk factors found. CONCLUSIONS: Among MHV patients on warfarin treatment with a sub-optimal quality of anticoagulation, the rate of PVD is 1.04 % pt-years, and the most frequent associated risk factor for PVD occurrence is warfarin withdrawal lasting more than one week.

Predictors for the prescription of pharmacological prophylaxis for venous thromboembolism during hospitalization in Internal Medicine: a sub-analysis of the FADOI-NoTEVole study.

Patients hospitalized in Internal Medicine Units (IMUs) may frequently experience both an increased risk for thrombosis and bleeding. The use of risk assessment models (RAMs) could aid their management. We present a post-hoc analysis of the FADOI-NoTEVole study, an observational, retrospective, multi-center study conducted in 38 Italian IMUs. The primary aim of the study was to evaluate the predictors associated with the prescription of thromboprophylaxis during hospitalization. The secondary objective was to evaluate RAMs adherence. Univariate analyses were conducted as preliminary evaluations of the variables associated with prescribing pharmacological thromboprophylaxis during hospital stay. The final multivariable logistic model was obtained by a stepwise selection method, using 0.05 as the significance level for entering an effect into the model. Thromboprophylaxis was then correlated with the RAMs and the number of predictors found in the multivariate analysis. Thromboprophylaxis was prescribed to 927 out of 1387 (66.8%) patients with a Padua Prediction score (PPS) ≥ 4. Remarkably, 397 in 1230 (32.3%) patients with both PPS ≥ 4 and an IMPROVE bleeding risk score (IBS) < 7 did not receive it. The prescription of thromboprophylaxis mostly correlated with reduced mobility (OR 2.31; 95% CI 1.90-2.81), ischemic stroke (OR 2.38; 95% CI 1.34-2.91), history of previous thrombosis (OR 2.46; 95% CI 1.49-4.07), and the presence of a central venous catheter (OR 3.00; 95% CI 1.99-4.54). The bleeding risk assessment using the IBS did not appear to impact physicians' decisions. Our analysis provides insight into how indications for thromboprophylaxis were determined, highlighting the difficulties faced by physicians with patients admitted to IMUs.

Trials of interventions for ovarian and testicular germ cell tumors registered in ClinicalTrials.gov: A cross-sectional study.

INTRODUCTION: There is unmet need in the treatment of ovarian and testicular germ cell tumors (GCTs). This study analyzed registered trials of interventions for GCTs. MATERIALS AND METHODS: We included trials of interventions for GCTs registered on ClinicalTrials.gov by July 29, 2022. We analyzed their interventions, outcome measures and study design. RESULTS: We included 142 trials registrations; 42 (30 %) for ovarian GCTs, 50 (35 %) for testicular GCTs, and 50 (35 %) trials for both. The majority of the trials were completed (56 %) and did not have results available (75 %). Most trials were in Phase 2. Information about the study design were not reported for many analyzed trials. Most trials had a single-group assignment (44 %) and were open-label (68 %). The median planned number of enrolled participants was 43. Most registrations used medicine(s) (87 %), either as a single type of intervention or in combination. The most commonly used type of medicine was chemotherapy (54 %). Primary outcome was not reported in 23 % of registrations, and secondary outcomes were not reported in 35 % of registrations. Overall survival was used in 6 % of registrations as a primary outcome and in 31 % of registrations as a secondary outcome. CONCLUSIONS: Few trials on GCTs were registered on ClinicalTrials.gov, and their number was declining in recent times. Most registrations did not report relevant information about the study design, or results if completed. More effort is needed to foster trials on GCTs, as well as to optimize the management of the registrations and foster the publication of research results.

Anticoagulant Therapy in Pregnant Women with Mechanical Heart Valves: Italian Federation of Centers for Diagnosis and Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.

The management of anticoagulant therapy in pregnant women with mechanical heart valves (MHVs) is difficult and often challenging even for clinicians experienced in the field. These pregnancies, indeed, are burdened with higher rates of complications for both the mother and the fetus, compared to those in women without MHVs. The maternal need for an optimal anticoagulation as provided by vitamin K antagonists is counterbalanced by their teratogen effect on the embryo and fetus. On the other hand, several concerns have been raised about the efficacy of heparins in pregnant women with MHVs, considering the high risk of thrombotic complications in these patients. Therefore, numerous clinical issues about the management of pregnant women with MHVs remain unanswered, such as the selection of the best anticoagulant agent, the optimal anticoagulation levels to be achieved and maintained, and the evaluation of long-term effects for both the mother and the fetus. Based on a comprehensive review of the current literature, the Italian Federation of the Centers for the Diagnosis and the Surveillance of the Antithrombotic Therapies (FCSA) proposes experience-based suggestions and expert opinions. Particularly, this consensus document aims at providing practical guidance for clinicians dealing with pregnant women with MHVs, to optimize maternal and fetal outcomes while guaranteeing adequate anticoagulation. Finally, FCSA highlights the need for the creation of multidisciplinary teams experienced in the management of pregnant women with MHVs during pregnancy, delivery, and postpartum, in order to better deal with such complex clinical issues and provide a comprehensive counseling to these patients.

Practical Suggestions for an Optimal Management of Vitamin K Antagonists: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.

In the era of direct oral anticoagulants, vitamin K antagonists retain a clinically relevant role in thrombotic disorders. In Italy, approximately 20% of the patients on anticoagulant therapies receives a VKA, in most cases warfarin. The optimal management of this drug is challenging and cannot disregard its intricate and unpredictable pharmacokinetic properties and patient's thrombotic and bleeding risk. Several clinical issues encountered during warfarin treatment are still unanswered and are tentatively addressed by physicians. In this regard, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) provides some experience-based good clinical practice's suggestions on the following topics: (1) how to start the anticoagulant treatment with warfarin and warfarin induction regimen; (2) how to manage a subtherapeutic INR value; (3) how to manage a supratherapeutic INR value in asymptomatic patients; and (4) how to manage the association of warfarin with interfering drugs.

The Clinical Impact of the Pulmonary Embolism Severity Index on the Length of Hospital Stay of Patients with Pulmonary Embolism: A Randomized Controlled Trial.

BACKGROUND: The Pulmonary Embolism Severity Index (PESI) is an extensively validated prognostic score, but impact analyses of the PESI on management strategies, outcomes and health care costs are lacking. Our aim was to assess whether the adoption of the PESI for patients admitted to an internal medicine ward has the potential to safely reduce the length of hospital stay (LOS). METHODS: We carried out a multicenter randomized controlled trial, enrolling consecutive adult outpatients diagnosed with acute PE and admitted to an internal medicine ward. Within 48 h after diagnosis, the treating physicians were randomized, for every patient, to calculate and report the PESI in the clinical record form on top of the standard of care (experimental arm) or to continue routine clinical practice (standard of care). The ClinicalTrials.gov identifier is NCT03002467. RESULTS: This study was prematurely stopped due to slow recruitment. A total of 118 patients were enrolled at six internal medicine units from 2016 to 2019. The treating physicians were randomized to the use of the PESI for 59 patients or to the standard of care for 59 patients. No difference in the median LOS was found between the experimental arm (8, IQR 6-12) and the standard-of-care arm (8, IQR 6-12) (p = 0.63). A pre-specified secondary analysis showed that the LOS was significantly shorter among the patients who were treated with DOACs (median of 8 days, IQR 5-11) compared to VKAs or heparin (median of 9 days, IQR 7-12) (p = 0.04). CONCLUSIONS: The formal calculation of the PESI in the patients already admitted to internal medicine units did not impact the length of hospital stay.

Rates of venous thromboembolism and use of thromboprophylaxis after major orthopedic surgery in patients with congenital hemophilia A or B: a systematic review.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognized complication after total joint replacement (TJR). Persons with hemophilia A or B are considered at low postoperative VTE risk due to their coagulation factor deficiencies, and administering pharmacologic thromboprophylaxis is often considered contraindicated. However, using factor replacement therapy could increase the postoperative VTE risk. OBJECTIVES: To analyze best available evidences of VTE rates in persons with hemophilia A or B undergoing lower limb TJR and the use of postoperative pharmacologic thromboprophylaxis. METHODS: We systematically screened 4 online biomedical databases to identify studies reporting VTE rates in patients with hemophilia after TJR. Case reports and case series with less than 10 patients were excluded. RESULTS: Twenty-six observational studies were included in this systematic review, reporting 1181 TJRs in patients with hemophilia A or B. Eight studies had VTE rates as the primary outcome. Five studies reported screen-detected VTE, while 21 reported symptomatic VTE events. Overall, 17 VTE events were reported (1.4%; 95% CI, 0.9%-2.3%), including 10 (6.6%) after 151 surgeries with postoperative VTE screening and 7 (0.7%) after 1080 surgeries without postoperative screening. Thromboprophylaxis protocols were specified in 21 studies; postoperative thromboprophylaxis was used in 15 (1.3%) surgeries. This information was not available for 29.0% of the analyzed population. CONCLUSION: Despite the low thromboprophylaxis use in patients with hemophilia, rates of symptomatic VTE after TJR appeared to be low. We also highlighted the need to better report the thrombotic outcome in persons with hemophilia to face the ongoing changes in the hemophilia landscape.

Efficacy and safety of prophylactic anticoagulation in patients with primary nephrotic syndrome: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Nephrotic syndrome (NS) is associated with an increased incidence of venous thromboembolism (VTE), approximately 10%. We performed a systematic review to evaluate the efficacy and safety of prophylactic anticoagulation in patients with NS. METHODS: Studies evaluating prophylactic anticoagulation in NS were identified by an electronic search of MEDLINE and EMBASE databases until December 2021. Weighted mean proportion and 95% confidence intervals (CIs) of thromboembolic and haemorrhagic events were calculated using a fixed-effects and a random-effects model. The differences in the outcomes among groups were estimated as pooled odds ratio (OR) and corresponding 95% CI. Statistical heterogeneity was evaluated using the I2 statistic. RESULTS: Five cohort studies, for a total of 414 adult patients, were included. Only two studies had a control group. The weighted mean incidence of pulmonary embolism (PE) and deep vein thrombosis in patients who received VTE prophylaxis was 1.8% (95% CI: 0.6-3.5%; I2 : 4.4%) and 0.9% (95% CI: 0.2-2.2%; I2 : 43.4%) respectively. The weighted mean incidence of major bleeding in patients who received VTE prophylaxis was 2.3% (95% CI: 1-4.2%; I2 : 25.4%). Patients with NS that received VTE prophylaxis had a non-significant reduced risk of PE (OR: 0.63 (95% CI: 0.03-14.8; I2 : 64.4%)) and an increased risk of major bleeding (OR: 2.08 (95% CI: 0.41-10.45; I2 : 0%)) compared to patients with NS that did not receive VTE prophylaxis. CONCLUSIONS: Our findings suggest that prophylactic anticoagulation in adult patients with primary NS may reduce the risk of VTE, even if it may be associated with a not negligible bleeding risk.

Guided Anti-P2Y12 Therapy in Patients Undergoing PCI: Three Systematic Reviews with Meta-analyses of Randomized Controlled Trials with Homogeneous Design.

BACKGROUND: The value of guided therapy (GT) with anti-P2Y12 drugs in percutaneous coronary intervention (PCI) is unclear. Meta-analyses lumped together randomized controlled trials (RCTs) with heterogeneous designs, comparing either genotype-GT or platelet function test (PFT)-GT with unguided therapy. Some meta-analysis also included RCTs that did not explore GT, but included the effects of switching patients with high on-treatment platelet reactivity (HTPR) to alternative therapies (HTPR-Therapy). We performed three distinct systematic reviews/meta-analyses, each exploring only RCTs with homogeneous design. METHODS: MEDLINE, Embase, and Central databases were searched for RCTs testing genotype-GT, PFT-GT, or HTPR-Therapy in PCI-treated patients, through October 1, 2022. Two reviewers extracted the data. Risk ratios (RRs) (95% confidence intervals) were calculated. Primary outcomes were major bleedings (MBs) and major adverse cardiovascular events (MACE). RESULTS: In seven genotype-GT RCTs, RRs were: MB, 1.06 (0.73-1.54; p = 0.76); MACE, 0.65 (0.47-0.91; p = 0.01), but significant risk reduction was observed in RCTs performed in China (0.30, 0.16-0.54; p < 0.0001) and not elsewhere (0.75, 0.48-1.18; p = 0.21). In six PFT-GT RCTs, RRs were: MB, 0.91 (0.64-1.28, p = 0.58); MACE, 0.82 (0.56-1.19; p = 0.30): 0.62 (0.42-0.93; p = 0.02) in China, 1.08 (0.82-1.41; p = 0.53) elsewhere. In eight HTPR-Therapy RCTs, RRs were: MB, 0.71 (0.41-1.23; p = 0.22); MACE, 0.57 (0.44-0.75; p < 0.0001): 0.56 (0.43-0.74, p < 0.0001) in China, 0.58 (0.27-1.23, p = 0.16) elsewhere. CONCLUSION: No GT strategy affected MB. Overall, genotype-GT but not PFT-GT reduced MACE. However, genotype-GT and PFT-GT reduced MACE in China, but not elsewhere. PFT-GT performed poorly compared to HTPR-Therapy, likely due to inaccurate identification of HTPR patients by PFT.

Tas-102 for Refractory Metastatic Colorectal Cancer: A Multicenter Retrospective Cohort Study.

Trifluridine/tipiracil (TAS-102) is an oral chemotherapy approved for the treatment of metastatic colorectal cancer. The efficacy and tolerability of TAS-102 were shown in phase II-III clinical trials and in several real-life studies. The elderly and other special subgroups are underrepresented in published literature. We conducted a retrospective multicenter study to assess the effectiveness and safety of TAS-102 in consecutive patients with pretreated mCRC. In particular, we estimated the effectiveness and safety of TAS-102 in elderly patients (aged ≥70, ≥75 and ≥80 years) and in special subgroups, e.g., patients with concomitant heart disease. One hundred and sixty patients were enrolled. In particular, 71 patients (44%) were 70 years of age or older, 50 (31%) were 75 years of age or older, and 23 (14%) were 80 years of age or older. 19 patients (12%) had a concomitant chronic heart disease, three (2%) patients were HIV positive, and one (<1%) patient had a DPYD gene polymorphism. In 115 (72%) cases TAS-102 was administered as a third-line treatment. The median overall survival (OS) in the overall population was 8 months (95% confidence interval [CI], 6-9), while the median progression-free survival (PFS) was 3 months (95% CI, 3-4). No significant age-related reduction in effectiveness was observed in the subpopulations of elderly patients included. The toxicity profile was acceptable in both the whole and subgroups' population. Our study confirms the effectiveness and safety of TAS-102 in patients with pretreated mCRC, suggesting a similar risk-benefit profile in the elderly.

A Peculiar CLL Case with Complex Chromosome 6 Rearrangements and Refinement of All Breakpoints at the Gene Level by Genomic Array: A Case Report.

INTRODUCTION: Chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries, is a mature B-cell chronic lymphoproliferative disorder characterized by the accumulation of neoplastic CD5+ B lymphocytes, functionally incompetent and usually monoclonal in origin, in bone marrow, lymph nodes and blood. Diagnosis occurs predominantly in elderly patients, with a median age reported between 67 and 72 years. CLL has a heterogeneous clinical course, which can vary from indolent to, less frequently, aggressive forms. Early-stage asymptomatic CLL patients do not require immediate therapeutic intervention, but only observation; treatment is necessary for patients with advanced disease or when "active disease" is observed. The most frequent autoimmune cytopenia (AIC) is autoimmune haemolytic anaemia (AHIA). The main mechanisms underlying the appearance of AIC in CLL are not fully elucidated, the predisposition of patients with CLL to suffering autoimmune complications is variable and autoimmune cytopenia can precede, be concurrent, or follow the diagnosis of CLL. CASE PRESENTATION: A 74-year-old man was admitted to the emergency room following the finding of severe macrocytic anaemia during blood tests performed that same day, in particular the patient showed a profound asthenia dating back several months. The anamnesis was silent and the patient was not taking any medications. The blood examination showed an extremely high White Blood Cell count and findings of AIHA in CLL-type mature B-cell lymphoproliferative neoplasia. Genetic investigations: Conventional karyotyping was performed and it obtained a trisomy 8 and an unbalanced translocation between the short arm of chromosome 6 and the long arm of chromosome 11, concurrent with interstitial deletions in chromosomes 6q and 11q that could not be defined in detail. Molecular cytogenetics (FISH) analyses revealed Ataxia Telangiectasia Mutated (ATM) monoallelic deletion (with loss of ATM on derivative chromosome 11) and retained signals for TP53, 13q14 and centromere 12 FISH probes. TP53 and IGHV were not mutated. Array-CGH confirmed trisomy of the entire chromosome 8 and allowed us to resolve in detail the nature of the unbalanced translocation, revealing multiple regions of genomic losses on chromosomes 6 and 11. DISCUSSION: The present case report is an unusual CLL case with complex karyotype and refinement of all breakpoints at the gene level by the genomic array. From a genetic point of view, the case under study presented several peculiarities. CONCLUSIONS: We report the genetic findings of a CLL patient with abrupt disease onset, so far responding properly to treatments despite the presence of distinct genetic adverse traits including ATM deletion, complex karyotype and chromosome 6q chromoanagenesis event. Our report confirms that interphase FISH alone is not able to provide an overview of the whole genomic landscape in selected CLL cases and that additional techniques are required to reach an appropriate cytogenetic stratification of patients.

Venous and arterial thromboembolic risk of Janus kinase inhibitors: a systematic review with meta-analysis.

OBJECTIVE: Preliminary data led licencing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of Janus kinase (JAK) inhibitors (JAKi). We performed a systematic review to estimate the risk of venous and arterial thrombosis associated to JAKi for the treatment of immune-mediated inflammatory diseases (IMIDs). METHODS: Randomized controlled trials (RCTs) on JAKi in patients with IMIDs were identified by the MEDLINE and EMBASE databases until October 2021. Risk of bias was assessed according to Cochrane criteria. The beta-binomial model was applied to calculate pooled odds ratio (OR) and corresponding 95% CI. The PROSPERO registration number is CRD42022324143. RESULTS: We have included one phase I, 21 phase II, three phase II-III and 36 phase III RCTs for a total of 19 443 patients in the JAKi group and 6354 in the control group. Thirty-one (unweighted rate 0.16%; 95% CI: 0.10, 0.21) events were reported in the JAKi group and 20 (unweighted rate 0.22%; 95% CI: 0.12, 0.32) in the control group in a mean follow-up of 16.8 weeks. IMID patients treated with JAKi did not have an increased thromboembolic risk compared with those treated with placebo (OR 0.82; 95% CI: 0.43, 1.56). No statistically different results were seen in subanalyses for each investigated IMID, drug and dosage. CONCLUSION: JAKi do not increase thromboembolic risk compared with placebo in IMID patients enrolled in selected RCTs.

Direct oral anticoagulants in patients with a left-sided bioprosthetic heart valve: a systematic review and meta-analysis.

To compare the efficacy/effectiveness and safety of DOACs versus VKAs in patients with a previously and newly surgically implanted BHV with or without AF. A systematic search on MEDLINE and EMBASE was performed till November 2022. Treatment effects were estimated with relative risk (RR) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed with the I2 statistic. Four randomized controlled trials (RCTs), 2 subgroup analysis from ARISTOTLE and ENGAGE-AF-TIMI 48 and 4 observational studies were included for a total of 5808 patients, 1893 on DOACs and 3915 on VKAs. AF prevalence was 98.28%. In the overall analysis, DOACs vs VKAs were associated with a RR for stroke/transient ischemic attack (TIA)/systemic embolism (SE) of 0.63 (95% CI 0.51-0.79; I2 = 0%) and a RR of major bleeding of 0.50 (95% CI 0.39-0.63; I2 = 0%) in a median follow-up of 19 months (IQR 4.5-33.4). In the 3 RCTs (DAWA, RIVER, ENAVLE), DOACs vs VKAs were associated with a RR of stroke/TIA/SE and major bleeding of 0.38 (95% CI 0.13-1.58, I2 = 0%) and of 0.68 (95% CI 0.32-1.44; I2 = 5%) respectively. In patients randomized during the first three months from valve surgery, DOACs vs VKAs were associated with a RR of stroke/TIA/SE and major bleeding of 0.54 (95% CI 0.14-2.08; I2 = 0%) and of 0.76 (95% CI 0.05-10.72; I2 = 66%). In previously implanted BHV patients with AF, DOACs showed a risk-benefit profile at least comparable to VKAs. DOACs showed a similar, even if underpowered, risk-benefit profile during the first three months after BHV implantation prevalently in patients with AF.

Diagnostic Accuracy of V/Q and Q SPECT/CT in Patients with Suspected Acute Pulmonary Embolism: A Systematic Review and Meta-analysis.

BACKGROUND: Computed tomography (CT) pulmonary angiography has simplified the diagnostic approach to patients with clinically suspected acute pulmonary embolism (PE), but alternative imaging tests are still advocated. We aimed to systematically assess the diagnostic accuracy of ventilation/perfusion (V/Q) and Q single-photon emission CT combined with low-dose CT (SPECT/CT) for PE diagnosis. METHODS: Studies evaluating the diagnostic accuracy of SPECT/CT for the diagnosis of acute PE were systematically searched in MEDLINE and EMBASE databases (up to August 2022). The QUADAS-2 tool was used for risk-of-bias assessment of the primary studies. A bivariate random-effects regression approach was used for summary estimates of both sensitivity and specificity. The PROSPERO registration number is CRD42021276538. RESULTS: Eight studies, for a total of 1,086 patients, were included. The risk of bias of all included studies was high. The weighted mean prevalence of PE was 27.1% at the random-effects model. The SPECT/CT bivariate weighted mean sensitivity was 96% (95% confidence interval [CI]: 93-98%), with a bivariate weighted mean specificity of 95% (95% CI: 90-97%). At subgroup analysis, for V/Q SPECT/CT bivariate weighted mean sensitivity and specificity were 96% (95% CI: 89-98%) and 96% (95% CI: 91-99%), while for Q SPECT/CT they were 96% (95% CI: 92-98%) and 84% (95% CI: 66-93%), respectively. CONCLUSION: V/Q SPECT/CT has high sensitivity and specificity for the diagnosis of acute PE, meanwhile Q SPECT/CT has high sensitivity but limited specificity for the diagnosis of PE. Management studies will conclusively ascertain the actual role of SPECT/CT in the diagnostic workup of patients with suspected acute PE.

Patient safety implications of wearing a face mask for prevention in the era of COVID-19 pandemic: a systematic review and consensus recommendations.

In the past, the use of face masks in western countries was essentially limited to occupational health. Now, because of the COVID-19 pandemic, mask-wearing has been recommended as a public health intervention. As potential side effects and some contraindications are emerging, we reviewed the literature to assess the impact of them in daily life on patient safety and to provide appropriate guidelines and recommendations. We performed a systematic review of studies investigating physiological impact, safety, and risk of masks in predefined categories of patients, which have been published in peer-reviewed journals with no time and language restrictions. Given the heterogeneity of studies, results were analyzed thematically. We used PRISMA guidelines to report our findings. Wearing a N95 respirator is more associated with worse side effects than wearing a surgical mask with the following complications: breathing difficulties (reduced FiO2, SpO2, PaO2 increased ETCO2, PaCO2), psychiatric symptoms (panic attacks, anxiety) and skin reactions. These complications are related to the duration of use and/or disease severity. Difficulties in communication is another issue to be considered especially with young children, older person and people with hearing impairments. Even if benefits of wearing face masks exceed the discomfort, it is recommended to take an "air break" after 1-2 h consecutively of mask-wearing. However, well-designed prospective studies are needed. The COVID-19 pandemic could represent a unique opportunity for collecting large amount of real-world data.

Oral anticoagulant management of patients with mechanical heart valves at the Salam Centre of Khartoum: Observations on quality of anticoagulation and thrombotic risk.

INTRODUCTION: Rheumatic heart disease with mechanical heart valve (MHV) replacement is common in Africa. However, MHV requires long-life anticoagulation and managing this can be challenging. METHODS AND RESULTS: We report data of a prospective observational study conducted between August 2018 and September 2019 in MHV patients in the Salam Centre for Cardiac Surgery built in Khartoum, by Emergency, an Italian Non-Governmental Organization, to evaluate the quality of anticoagulation control and the risk of thrombotic complications. RESULTS: We studied 3647 patients (median age 25.1 years; 53.9 % female). Median Time in Therapeutic Range (TTR) was 53 % (interquartile range 37 % to 67 %) and 70 thrombotic events (rate 1.8 × 100 pt-years [95 % CI 1.38-2.23]) were recorded. Among patients in the first quartile of TTR (≤37 %), we recorded 34/70 (48.6 %) of all thrombotic events (rate 3.7 × 100 pt-years [95 % CI 2.5-5.1]), with a high mortality rate (2.2 × 100 pt-years [95 % CI 1.3-3.3]). In patients with guideline-recommended TTR (≥65 %) the event rate was 0.8 × 100 pt-years for thrombotic events [95 % CI 0.3-1.5] and 0.4 × 100 pt-years for mortality [95 % CI 0.1-0.9]. Multivariable analysis showed that having a TTR in the lowest quartile (≤37 %) and being noncompliant are significantly associated with increased thrombotic risk. Aspirin use or different valve type did not influence the thrombotic risk. Almost 40 % of all thromboembolic complications could have been potentially prevented by further improving VKA management to obtain a TTR > 37 %. CONCLUSION: The thrombotic risk of MHV patients on VKAs living in a low-income country like Sudan is associated with low quality of anticoagulation control. Efforts should be made to decrease the number of non-compliant patients and to reach a guideline-recommended TTR of ≥65 %.