WAYS OF STRENGHTENING THE STATUTORY AUDIT EFFICIENCY

The integrity of the auditor’s opinion and the audit process conducting effectivenesshangs on the professional judgment applied on obtaining, processing and interpreting the internal andexternal information. Documentation is based on all the audit evidence collected through proceduressuch as: inspection, confirmation, documentation etc. Audit evidence is used to determine whether thefinancial statements present the economic reality of transactions and if they faithfully reflect thefinancial position of the company. To achieve a reasonable assurance, the auditor should gathersufficient and high quality audit evidence so that the view expressed in the report of the independentauditor should be based on a credible and relevant background.audit evidence, audit procedures, professional judgment, reasonable assurance.

A Site Evaluation Campaign for a Ground Based Atmospheric Cherenkov Telescope in Romania

Around the world, several scientific projects share the interest of a global network of small Cherenkov telescopes for monitoring observations of the brightest blazars - the DWARF network. A small, ground based, imaging atmospheric Cherenkov telescope of last generation is intended to be installed and operated in Romania as a component of the DWARF network. To prepare the construction of the observatory, two support projects have been initiated. Within the framework of these projects, we have assessed a number of possible sites where to settle the observatory. In this paper we submit a brief report on the general characteristics of the best four sites selected after the local infrastructure, the nearby facilities and the social impact criteria have been applied.Comment: 6 pages, 5 Postscript figure

Arrhythmias and conduction disturbances in patients with systemic sclerosis—A systematic literature review

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis and microvascular impairment, which can affect major organs, including the heart. Arrhythmias are responsible for approximately 6% of deaths in patients with SSc, and mainly occur due to myocardial fibrosis, which causes electrical inhomogeneity. The aim of this study was to determine the frequency of arrhythmias and conduction disturbances in SSc cohorts, and to identify the characteristics and risk factors associated with the occurrence of dysrhythmias in patients with SSc. A systematic literature review using PubMed, Embase, Web of Science and Scopus databases was performed. Full-text articles in English with arrhythmias as the main topic published until 21 April 2022 were included. Most prevalent arrhythmias were premature supraventricular and ventricular contractions, while the most frequent conduction disturbance was represented by right bundle branch block (RBBB). Elevated concentrations of N-terminal prohormones of brain natriuretic peptides (NT-pro BNP) were associated with numerous types of atrial and ventricular arrhythmias, and with the occurrence of RBBB. A lower value of the turbulence slope (TS) emerged as an independent predictor for ventricular arrhythmias. In conclusion, dysrhythmias are frequent in SSc cohorts. Paraclinical and laboratory parameters are useful instruments that could lead to early diagnosis in the course of the disease

Cutaneous Adverse Reactions to TNF Alpha Blockers. Case Report and Literature Review

Biological therapy is used in a wide range of medical settings. Adverse reactions to biological therapy can limit their widespread use, so early detection and treatment can adjust attempts to stop these molecules. TNF Alpha blockers may cause the following skin reactions in alpha patients: injection site reactions, infections, immune-mediated reactions (psoriasis, psoriasis, drug-induced lupus, vasculitis, hidradenitis, alopecia), allergic or neoplastic reactions. We present the case of a patient with RA who developed skin lesions during biological therapy and was diagnosed with drug-induced lupus based on clinical elements, associated autoimmunity, and dermatological evaluation. The skin lesions were attributed to the interaction of three medications (biosimilar Etanercept, Leflunomide, and Isoniazid), all of which have been implicated in causing these side effects. The solutions that saved the patient were temporarily discontinuing the immunosuppressive medication and replacing it with a local corticoid, followed by the continuation of Etanercept in associated with Methotrexate, and the patient was able to continue the biological medication and obtain a favorable response to the treatment. In conclusion, skin changes caused by TNF Alpha inhibitors are common, but vary in severity, and do not warrant therapy interruption

Arrhythmias and Conduction Disturbances in Patients with Systemic Sclerosis—A Systematic Literature Review

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis and microvascular impairment, which can affect major organs, including the heart. Arrhythmias are responsible for approximately 6% of deaths in patients with SSc, and mainly occur due to myocardial fibrosis, which causes electrical inhomogeneity. The aim of this study was to determine the frequency of arrhythmias and conduction disturbances in SSc cohorts, and to identify the characteristics and risk factors associated with the occurrence of dysrhythmias in patients with SSc. A systematic literature review using PubMed, Embase, Web of Science and Scopus databases was performed. Full-text articles in English with arrhythmias as the main topic published until 21 April 2022 were included. Most prevalent arrhythmias were premature supraventricular and ventricular contractions, while the most frequent conduction disturbance was represented by right bundle branch block (RBBB). Elevated concentrations of N-terminal prohormones of brain natriuretic peptides (NT-pro BNP) were associated with numerous types of atrial and ventricular arrhythmias, and with the occurrence of RBBB. A lower value of the turbulence slope (TS) emerged as an independent predictor for ventricular arrhythmias. In conclusion, dysrhythmias are frequent in SSc cohorts. Paraclinical and laboratory parameters are useful instruments that could lead to early diagnosis in the course of the disease

Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis : results from a European collaborative study

Objectives To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. Methods Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were included. According to baseline data, patients were considered as taking TCZ as monotherapy or combination with sDMARDs. Main study outcomes were the change of Clinical Disease Activity Index (CDAI) and TCZ retention. The prescription of TCZ as monotherapy was analysed using logistic regression. CDAI change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. Results Multiple-adjusted analysis suggests that prescription of TCZ as monotherapy varied according to age, corticosteroid use, country of the registry and year of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2.3 years (95% CI 1.8 to 2.7) for monotherapy and 3.7 years (lower 95% CI limit 3.1, upper limit not estimable) for combination therapies. In a covariate-adjusted analysis, TCZ retention was also reduced when used as monotherapy, with an increasing difference between mono and combination therapy over time after 1.5 years (p=0.002). Conclusions TCZ with or without concomitant sDMARDs resulted in comparable clinical response as assessed by CDAI change, but TCZ retention was shorter under monotherapy of TCZ.Peer reviewe

Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort : data from the CERERRA collaboration

Background: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg x 2, but some data have suggested similar clinical efficacy with 500 mg x 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. Methods: Twelve European registries participating in the CERERRA collaboration (The European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Treatment effectiveness was assessed by DAS28 reductions and EULAR responses after 6 months. Results: Data on RTX dose were available for 2,873 patients, of whom 2,625 (91.4 %) and 248 (8.6 %) received 1000 mg x 2 and 500 mg x 2, respectively. Patients treated with 500 mg x 2 were significantly older, had longer disease duration, higher number of prior DMARDs, but lower number of prior biologics and lower baseline DAS28 than those treated with 1000 mg x 2. Fewer patients in the low-dose group received concomitant DMARDs but more frequently received concomitant corticosteroids. Both doses led to significant clinical improvements at 6 months. DAS28 reductions at 6 months were comparable in the 2 dose regimens [mean DeltaDAS28 +/- SD -2.0 +/- 1.3 (high dose) vs. -1.7 +/- 1.4 (low dose), p = 0.23 adjusted for baseline differences]. Similar percentages of patients achieved EULAR good response in the two dose groups, 18.4 % vs. 17.3 %, respectively (p = 0.36). Conclusions: In this large observational cohort initial treatment with RTX at 500 mg x 2 and 1000 mg x 2 led to comparable clinical outcomes at 6 months.Peer reviewe

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

MANAGEMENTUL PACIENTULUI CU POLIARTRITA REUMATOIDA IN ROMANIA

Introduction. Rheumatoid Arthritis is a chronic disease with long evolution which produces important consequences at the level of patient and society, a disease with several available therapeutic options, but not all of them having the same effects. The therapeutic measures are applied on a long term basis and they are, in most of the time, the result of medical practice guidelines developed at local or international level. Methods. The authors made a revision of the local and international speciality literature regarding rheumatoid arthritis and studied the legal framework in Romania regarding the medical practice guidelines, therapeutic protocols and treatment reimbursement conditions.   Results. In Romania the management of patient with rheumatoid arthritis is based on several clinical and administrative decisions, reflected into the medical practice guidelines and therapeutic protocols with normative value. Because of high costs, the availability of biologic therapies for the rheumatoid arthritis patients is restricted only to these patients with approved treatment by the public payer, according to specific therapeutic protocols developed by the Ministry of Health and National Health Insurance House. The limited available financial resources in the social health insurance system create the conditions for waiting lists of the patients with medical recommendation for expensive therapies.  Conclusions. The management of patient with rheumatoid arthritis is a complex process related with patient factors, but also with the health system functionality. In Romania, the usage of newly and expensive treatments requires the utilization of some medical practice guidelines and therapeutic protocols which should rely more and more on the effectiveness rather than the efficacy of treatments, considering the fact that clinical data regarding effectiveness of drugs treatments started to be available. Key words: patient management, rheumatoid arthritis, efficacy, effectiveness therapeutic protocols, quality of lifeIntroducere. Poliartrita reumatoida este o boala cronica cu evolutie indelungata, ce are consecinte importante la nivel individual si social si la care optiunile terapeutice disponibile sunt multiple, dar nu toate produc aceleasi efecte. Masurile terapeutice recomandate se utilizeaza timp indelungat si sunt de cele mai multe ori rezultatul unor ghiduri de practica medicala, dezvoltate la nivel national sau international. Metodologie. Autorii au realizat o revizie a literaturii de specialitate privind poliartrita reumatoida la nivel mondial si in Romania si au studiat cadrul normativ in Romania privind ghidurile de practica medicala, protocoalele de tratament si conditiile de finantare  ale tratamentului bolii. Rezultate. Managementul pacientului cu poliartrita reumatoida in Romania presupune o serie de decizii clinice si administrative reflectate in ghiduri de practica si protocoale de tratament cu valoare normativa. In Romania, datorita costurilor ridicate, disponibilitatea terapiilor biologice la pacienti este conditionata de aprobarea tratamentului de catre tertul-platitor, pe baza unor protocoale terapeutice elaborate de Ministerul Sanatatii si Casa Nationala de Asigurari de Sanatate. Insuficienta resurselor financiare la nivelul sistemului asigurarilor sociale de sanatate face ca accesul la terapiile mai scumpe sa fie limitat si conditionat de existenta unor liste de asteptare. Concluzii. Managementul pacientului cu poliartrita reumatoida este un proces complex, conditionat de mai multi factori ce tin de pacient, dar si de functionalitatea sistemului de sanatate. Utilizarea in Romania a unor tratamente novatoare si costisitoare presupune urmarirea unor ghiduri de practica sau a unor protocoale, care sa se bazeze pe eficacitatea practica mai degraba decat pe eficacitatea clinica a tratamentelor, in conditiile in care incep sa fie disponibile date clinice privind efectele terapeutice ale acestor medicamente. Cuvinte cheie: managementul pacientului, poliartrita reumatoida, eficacitate, ghiduri de practica, protocoale terapeutice, calitatea vieti