Adherence to penicillin treatment is essential for effective secondary prevention of rheumatic heart disease: a systematic review and meta-analysis.

Background: Penicillin is essential for secondary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). However, the incidences of ARF recurrence and RHD progression remain high, particularly in endemic countries. This meta-analysis evaluated the effectiveness of penicillin adherence in secondary prevention of ARF recurrence and RHD progression. Methods: The authors included original articles employing an observational study design in which the study population included patients with ARF or RHD and documented adherence to secondary prophylaxis with penicillin for secondary prevention. Systematic searches of the PubMed, Scopus, and Cochrane databases were performed. Moreover, the authors also conducted a snowballing literature search from Europe PMC to expand the included studies. The quality of each study was assessed using the National Institute of Health Quality Assessment Tool. The statistical analyses were conducted using Review Manager 5.4.1 software developed by Cochrane. In addition, the authors utilized pooled odds ratios (ORs) to compare the adherence techniques. Results: A total of 310 studies were identified, of which 57 full-text articles were assessed for eligibility. The authors included six studies with 1364 patients for the qualitative synthesis and meta-analysis. Good adherence to penicillin for the secondary prophylaxis of ARF and RHD, significantly reduced the odds of ARF recurrence or RHD progression by up to 71% compared to that associated with poor adherence [pooled OR 0.29 (0.21-0.40); I²=0% (p=0.56); Z=7.64 (p <0.00001)]. Conclusion: Good adherence to penicillin for secondary prophylaxis in patients with ARF or RHD is essential for reducing the risk of ARF recurrence or RHD progression.

[First French-speaking days of users of decision support system in clinical pharmacy: Feedback and perspectives]. / Premières journées francophones des utilisateurs de système d'aide à la décision en pharmacie clinique : retour d'expériences et perspectives.

Clinical decision support systems (CDSS) are tools that have been used for several years by clinical pharmacy teams to support pharmaceutical analysis, with a perspective of contributing to the quality of care in collaboration with the other health care team members. These tools require both technical, logistical and human resources. The growing use of these systems in different establishments in France and in Europe gave birth to the idea of meeting to share our experiences. The days organized in Lille in September 2021 aimed at proposing a time of exchange and reflection on the use of these CDSS in clinical pharmacy. A first session was devoted to feedback from each establishment. These tools are essentially used to optimize pharmaceutical analysis and to secure patient medication management. This session outlined the clear advantages and common limitations of these CDSS. Two research projects were also presented to put the use of these tools into perspective. The second session of these days, in the form of workshops, addressed 4 themes that surround the implementation of CDSS: their usability, the legal aspect, the creation of rules and their possible valorization. Common problems were raised, the resolution of which requires close collaboration. This is a first step proposing a beginning of harmonization and sharing that should be deepened in order not to lose the dynamics created between the different centers. This event ended with the proposal to set up two working groups around these systems: the creation and structuring of rules for the detection of risk situations and the common valorization of the work.

The effect of external counterpulsation on intrinsic myocardial function evaluated by speckle tracking echocardiography in refractory angina patients: a randomized controlled trial.

External Counterpulsation (ECP) is one of the therapeutic options in patients with refractory angina inadequately controlled by medical, interventional, or surgical therapy. The 2D Speckle Tracking Echocardiography (2D-STE) method is considered superior in assessing clinical improvement. We would like to evaluate any improvement of myocardial intrinsic function using 2D-STE in patients underwent standard ECP protocol (35 sessions). We conducted a double-blind randomized controlled trial. Patients with refractory angina who could not be revascularized conventionally were randomized into two groups: (1) the ECP group (300 mmHg) and (2) the Sham/control group (75 mmHg). ECP standard therapy was given for 35 sessions (1 h/day/session). The 2D-STE data, including longitudinal strain and post systolic index (PSI) were obtained before and after therapy. 43 subjects were analyzed, with 22 subjects in ECP group and 21 control subjects (Sham group). A homogenous baseline strain was found either globally (12.42 ± 4.55 vs 12.00 ± 4.92 [- %]; P = 0.774) or segmentally/regionally (12.63 (0.01-25.16) vs 12.43 (0.01-27.20) [- %]; P = 0.570). There was no statistically significant improvement between groups in the left ventricle longitudinal strain globally (P = 0.535) and segmentally/regionally (P = 0.434). PSI parameters showed improvement in the ECP group (P = 0.049), and segments with PSI ≥ 20% seemed to improve longitudinal strains in the ECP group after therapy (P = 0.042). In conclusion, 35 ECP therapy sessions did not improve either global or segmental/regional left ventricular mechanical function in patients with refractory angina. However, the mechanical function of myocardial segments with PSS tends to improve after ECP therapy.

Severe adverse events during medical and surgical treatment of hip and knee prosthetic joint infections.

INTRODUCTION: The management of prosthetic joint infection requires a complex treatment procedure and can be associated with complications. However, the occurrence of severe adverse events during this intervention has been poorly evaluated. PATIENTS AND METHODS: A 5-year multicentric retrospective study including patients from 3 hospitals in the South-Western France referral center for complex bone and joint infections (Crioac GSO) and treated for hip or knee prosthetic joint infection with 1 or 2-stage implant exchanges. The objective was to describe grade≥3 adverse events, according to the CTCAE classification, occurring within 6 weeks after surgery and to identify their associated factors. RESULTS: One hundred and eighteen patients were identified. We observed 71 severe events in 50 patients (42.3%; 95% confidence interval [CI95%]: 33.8-51.4%). Sixteen severe events were an evolution of the infection. The remaining 55 others (47 grade 3 and 8 grade 4) occurred in 41 patients (34.7%; CI95%: 26.8-43.7%). They were distributed as follows: 27 (49.1%) medical complications, 21 (38.2%) surgical complications and 7 (12.7%) antibiotic-related complications. The main identified risk factor was a two-stage prosthetic exchange with OR=3.6 (CI95% [1.11-11.94], P=0.032). Obesity was limit of significance with OR=3.3 (CI95% [0.9-12.51], P=0.071). Infection with coagulase negative Staphylococcus was a protective factor with OR=0.3 (CI95% [0.12-0.99], P=0.047). CONCLUSION: Severe adverse events are frequent following prosthetic exchange for PJI (34.7%) and are related to the high frequency of comorbidities in this population and to the complex surgical procedures required. The risk factor significantly associated with these events was a two-stage exchange.

Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2.

Rheumatic heart disease (RHD) is common in developing countries and poses a big medical challenge and burden. The pathogenesis of RHD is influenced by the triad of host, agent, and environment. Autoantigens generated from Group A Streptococcus (GAS) infection are captured by the resident dendritic cells (DCs) in the heart's valvular endothelium. DCs differentiate into antigen presenting cells (APC) in the valve interstices. APC induces activation of autoreactive T cells, which triggers inflammation and tissue fibrosis. Cardiac fibrosis is promoted through the activation of Mitogen activated protein kinases (MAPKs) and its downstream signaling, including its interaction with transforming growth factor-ß (TGF-ß) and Smad proteins. TGF-ß-induced phosphorylation of Smad2 complexes with Smad3 and Smad4, and translocates into the nucleus. Angiotensin II enhances the migration, maturation, and presentation of DC. In RHD, Angiotensin II induces fibrosis via the stimulation of TGF-ß, which further increases the binding of IL-33 to sST2 but not ST2L, resulting in the upregulation of Angiotensin II and progression of cardiac fibrosis. This cascade of inflammation and valvular fibrosis causes calcification and stiffening of the heart valves in RHD. Angiotensin converting enzyme inhibitors (ACEIs) inhibit Angiotensin II production, which in turn decreases TGF-ß expression and the onset of overt inflammatory response. This condition leads to a reduction in the sST2 as the decoy receptor to "steal" IL-33, and IL-33 binds to ST2L and results in cardioprotection against cardiac fibrosis in the pathogenesis of RHD.

Detection of the emerging rotavirus G!@P(8) genotype at high frequency in brazil in 2014: Successive replacement of predominant strains after vaccine introduction

The continuum characterization of rotavirus (RVA) genotypes is essential to understand how vaccine introduction could impact virus epidemiology. In the present study, an unexpected rapid changing pattern of RVA genotypes distribution in Brazilian population during three followed seasons is described. From January/2012 to December/2014, a total of 3441 fecal specimens were collected from collaborating centers across Southern, Southeastern and Midwest of Brazil. All specimens were screened for RVA using ELISA, and genotyped by RT-PCR. Differences in proportions were tested using Chi-Squares. A p-value of less than 0.05 was considered statistically significant. RVA was detected in 19.7% (677/3441). Among RVA positive cases (n=677), a total of 652 (96.3%) samples were successfully amplified by RT-PCR. G3P[8] remained prevalent in 2012 (37.6%, 69/185) and 2013 (40.1%, 74/186) (χ(2)=0.107, p=0.743), but declined markedly in 2014 (3.5%, 10/281) (χ(2)=71.770, p=0.000). G12P[8] was second highest strain in 2012 (22.7%, 42/185), decrease rapidly in 2013 (2.7%, 5/186) (χ(2)=26.224, p=0.000) and re-emerged as the predominant genotype in 2014 (86.6%, 243/281) (χ(2)=118.299, p=0.000). From July/2014, G12P[8] was the single genotype detected in all regions studied. The sudden emergence, spread and predominance of G12P[8] strain in Brazil, raised the hypothesis of a possible G12 outbreak being in progress. Nationally, the long term decline in gastroenteritis hospitalization observed in the country after RVA vaccine introduction was confirmed. Nevertheless, the sharp increase in diarrhea hospitalization prevalence from 2013 to 2014 observed in Southern and Southeastern regions is consistent with what appears to be an outbreak of G12P[8]. Continued surveillance is needed to verify the effectiveness of the RotarixTM vaccine in Brazil together with potential emergence of unusual genotypes.

Effects of bradykinin and icatibant on renal hemodynamics in conscious spontaneously hypertensive and normotensive rats.

We investigated the effects of bradykinin (BK) and icatibant (HOE 140), a highly selective bradykinin-B2-receptor antagonist, on mean arterial blood pressure (MAP), heart rate (HR), renal blood flow (RBF), and renal vascular resistance (RVR) in conscious Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Experiments were performed in conscious male WKY rats and SHRs instrumented over the long term with arterial and venous catheters and a transit-time flow probe for measurement of RBF. In WKY rats (n = 16), intraaortic (i.a.) bolus injections of BK (0.1, 1.0, and 10 microg) produced dose-dependent decreases in MAP and RBF with reciprocal increases in RVR. Intrarenal (i.r.) injections of BK (10 microg; n = 6) induced the same hemodynamic response pattern, although the increase in RVR was higher compared with i.a. injections (p < 0.05). Neither vasopressin V1-receptor nor alpha1-adrenoceptor blockade had an effect on the renal vasoconstrictor responses on i.a. BK. The i.a. injections of icatibant (0.1, 1.0, 5.0, and 10 microg; n = 6-10 for each dose) led to a dose-dependent blockade of the hemodynamic responses to BK (10 microg, i.a.). Icatibant (10 microg, i.a) had no effect on resting MAP and HR but induced a biphasic response in RBF and RVR with significant changes compared with basal values (p < 0.05). In SHRs (n = 9), after injection of increasing i.a. doses of BK (0.1, 1.0, and 10 microg), dose-dependent decreases in MAP were proportionately greater compared with those in WKY rats. In contrast to WKY rats, RBF and RVR exhibited a biphasic response pattern on BK in SHRs. Neither vasopressin V1-receptor nor alpha1-adrenoceptor blockade had an effect on the renal vasoconstrictor responses on i.a. BK. The i.a. injections of icatibant (10 microg) almost completely blocked the hemodynamic responses on BK in SHRs (n = 13). Icatibant (10 microg, i.a.) itself induced an increase in resting MAP and HR (p < 0.05) and a biphasic response in RBF and RVR with significant changes of basal values (p < 0.05). Our results provide evidence that BK exhibits renal vasoconstrictor and vasodilator properties in vivo, both mediated by B2-receptors. Furthermore, we demonstrated that SHRs display an increased B2-receptor-mediated vasodilatory responsiveness to BK. Finally we showed that blockade of B2 receptors leads to an increase of MAP in SHRs in contrast to WKY rats, suggesting an important role of the kallikrein/kinin system in the regulation of high blood pressure in SHRs.