Evaluarea eficacităţii şi toleranţei preparatului „Lovex” în tratamentul pacienţilor cu disfuncţie erectilă

Summary Lovex, sildenafil citrat 70 mg, Faramco, R. Moldova was prescribed to 30 patients with erectile dysfunction (ED) including 10 patients with Chronic Renal Failure on hemodialysis. The efficacy of the drug was appreciated according to the IIEF questionnaire. Lavex has shown a good efficacy on 80% of patients, comparable with 100mg of sildenafil but with minimal adverse events and could be recommended as an election treatment in patients ED. Introducere. Pentru tratamentul disfuncţiei erectile (DE) au fost propuse m ai m ulte substanţe farm aceutice, farm acoterapia orală reprezentând la ora actuală prima opţiune de tratament al pacienţilor cu disfuncţie erectilă. începând cu anul 1998 primul medicament prescris cu succes în tratamentul DE, indiferent de etiologie a fost sildenafilul citrat, inhibitor selectiv al enzimei fosfodiesteraza tip 5. Actualmente sildenafilul citrat este prezent pe piaţa farmaceutică sub mai multe denumiri comerciale. Scopul lucrării. Aprecierea profilului de eficienţă şi de toleranţă în tratamentul DE a preparatului „Lovex”, sildenafil citrat 70 mg, produs de compania farmaceutică „Farmaco”, Republica Moldova. Material şi metodă. Studiul a fost efectuat în cadrul Catedrei de Urologe şi Nefrologie Chirurgicală a USMF „Nicolae Testemiţanu” pe un lot de 30 pacienţi cu disfuncţie erectilă, inclusiv 20 pacienţi ambulatori şi 10 pacienţi cu Insuficienţă Renală Cronică (IRC), supuşi hemodializei în cadrul Centrului Republican de Hemodializă şi Transplant Renal. Vârsta pacienţilor a variat de la 21 la 68 ani. Pentru a aprecia prezenţa disfuncţiei erectile, a gradului de dificultate şi a eficacităţii tratamentului a fost utilizat chestionarul IIEF (Internaţional Index of Erectile Function), care permite evaluarea screening a funcţiilor sexuale, independent de particularităţile socio-culturale sau de moment ale pacientului. Durata tulburărilor de erecţie a variat de la 3 luni la 5 ani. Disfuncţia erectilă uşoară a fost diagnosticată la 8 pacienţi, moderată - la 15 şi severă - la 7. Preparatul „Lovex” a fost administrat o dată în zi, cu o oră înaintea actului sexual. Evaluarea tratamentului a fost efectuată la 1 lună de la iniţierea sa, prin completarea repetată a chestionarului IIEF, a fişierului de apreciere a toleranţei, iar pacienţii cu IRC au fost monitoriţai suplimentar prin aprecierea indicelor T/A şi a unor constante bioumorale. în perioada susnumită fiecare pacient a luat între 4 şi 8 comprimate de „Lovex”. Rezultate. Analiza chestionarelor IIEF, postterapie, a demonstrat prezenţa unor efecte terapeutice importante. Astfel la întrebările 3, 4 şi 5 care se referă la capacitatea de a ajunge şi a menţine erecţia pe durata raportului sexual, 24 (80%) pacienţi au remarcat o ameliorare evidentă a funcţiei erectile, 6 (20%) nu au observat nici o schimbare, 14(46%) au raportat 0 creştere a libidoului, 21(70%) - o creştere evidentă a satisfacţiei de viaţă, iar 19 (63%) - o reapariţie a încrederii în capacitatea de a avea şi a menţine o erecţie. Dintre pacienţii cu IRC aflaţi la dializă, îmbunătăţirea erecţiei a fost semnalată în 90% cazuri. Toleranţa preparatului a fost în general bună. Efectele adverse au fost minime şi s-au manifestat prin cefalee moderată - 3 (10%) pacienţi, dispepsie - 2 (6,6%) pacienţi, congestie nazală - 1 pacient (3,3%), creşterea valorilor T/A - 1 pacient (3,3%). Nu am semnalat suspendarea tratamentului din cauza efectelor adverse. Discuţii şi concluzii. În termeni de comparaţie potenţa şi selectivitatea unui inhibitor al fosfodiesterazei tip 5 este CI50, ceea ce reprezintă concentraţia minim necesară a inhibitorului pentru a reduce eficienţa enzimei la 50%. Pentru a atinge un nivel de inhibare a PDE-5 de 90%, este necesară o concentraţie liberă plasmatică de circa 25nM sildenafil. O doză unică de sildenafil citrat de 100 mg determină o concentraţie plasmatică de vârf de circa 38nM. Majoritatea efectelor adverse raportate în literatura de specialitate se referă la doza respectivă. Dozarea de 70 mg a preparatului „Lovex” permite atingerea unui nivel înalt de inhibiţie al PDE-5, nu însă şi a efectelor adverse, care în studiul nostru sunt comparabile cu valorile de 50 mg sildenafil citrat. Ameliorarea mai evidentă a erecţiei la pacienţii cu IRC se explică, probabil, prin atingerea unei concentraţii plasm atice mai mari a sildenafilului la atare categorie de pacienţi, afirmaţie care necesită însă studii suplimentare. În concluzie, preparatul „Lovex” sildenafil citrat 70 mg, produs de compania farmaceutică „Farmaco”, are o eficacitate remarcabilă în tratamentul pacienţilor cu disfuncţie erectilă, comparabilă cu dozele de sildenafil de 100mg, dar cu efecte adverse minime şi poate fi recomandat ca preparat de primă linie terapeutică

Molybdenum-99 (99Mo) Adsorption Profile of Zirconia-Based Materials for 99Mo/99mTc Generator Application

Technetium-99m (99mTc) plays a major role in diagnostic nuclear medicine and has not yet been replaced with any other radionuclides. It is available through the 99Mo/99mTc generator. The use of low-specific-activity 99Mo for 99Mo/99mTc generator application requires high adsorptive capacity sorbents. This study focused on the determination of 99Mo adsorption capacity of several zirconia materials, namely monoclinic nanozirconia, orthorhombic nanozirconia, sulfated zirconia,   and phosphated zirconia. These materials were synthesized by using the sol-gel method and characterized using FT-IR spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM-EDS). The determination of 99Mo adsorption capacity of these materials was carried out by soaking the materials in a Na299MoO4 solution with pH of 3 and 7, at temperatures ranging from room temperature to 90 °C, for 1 and 3 hours. The results indicated that monoclinic nanozirconia has a 99Mo adsorption capacity of 76.9 mg Mo/g, whereas orthorhombic nanozirconia, sulfated zirconia, and phosphated zirconia have 99Mo adsorption capacities of 150.1 mg Mo/g, 15.58 mg Mo/g, and 12.74 mg Mo/g, respectively. It appears that orthorhombic nanozirconia has the highest 99Mo adsorption capacity among the synthesized materials and can be applied as a candidate material for the 99Mo/99mTc generator

Melphalan 140mg/m2 or 200mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

Melphalan at a dose of 200mg/m2 is standard conditioning prior to autologous haematopoietic stem cell transplantation for multiple myeloma, but a dose of 140mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine if melphalan 200 and melphalan 140 are equally effective and tolerable in clinically relevant patient subgroups we analysed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, haematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 (n=245) and melphalan 200 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 versus melphalan 140: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favoured melphalan 140 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 and melphalan 140 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favour melphalan 200 or melphalan 140 for key transplant outcomes (NCT01362972)

Low-Temperature Growth of Graphene on a Semiconductor

The industrial realization of graphene has so far been limited by challenges related to the quality, reproducibility, and high process temperatures required to manufacture graphene on suitable substrates. We demonstrate that epitaxial graphene can be grown on transition metal treated 6H-SiC(0001) surfaces, with an onset of graphitization starting around $450-500^\circ\text{C}$. From the chemical reaction between SiC and thin films of Fe or Ru, $\text{sp}^{3}$ carbon is liberated from the SiC crystal and converted to $\text{sp}^{2}$ carbon at the surface. The quality of the graphene is demonstrated using angle-resolved photoemission spectroscopy and low-energy electron diffraction. Furthermore, the orientation and placement of the graphene layers relative to the SiC substrate is verified using angle-resolved absorption spectroscopy and energy-dependent photoelectron spectroscopy, respectively. With subsequent thermal treatments to higher temperatures, a steerable diffusion of the metal layers into the bulk SiC is achieved. The result is graphene supported on magnetic silicide or optionally, directly on semiconductor, at temperatures ideal for further large-scale processing into graphene based device structures.Comment: 10 pages, 4 figures, 51 reference

Ethical procedures and patient consent differ in Europe

BACKGROUND: Research ethics approvals, procedures and requirements for institutional research ethics committees vary considerably by country and by type of organisation. OBJECTIVE: To evaluate the requirements and procedures of research ethics committees, details of patient information and informed consent based on a multicentre European trial. DESIGN: Survey of European hospitals participating in the prospective observational study on chronic postsurgical pain (euCPSP) using electronic questionnaires. SETTING: Twenty-four hospitals in 11 European countries. PARTICIPANTS: From the 24 hospitals, 23 local investigators responded; 23 answers were analysed. OUTCOME MEASURES: Comparison of research ethics procedures and committee requirements from the perspective of clinical researchers. Comparison of the institutions' procedures regarding patient information and consent. Description of further details such as costs and the duration of the approval process. RESULTS: The approval process lasted from less than 2 weeks up to more than 2 months with financial fees varying between 0 and 575 €. In 20 hospitals, a patient information sheet of variable length (half page up to two pages) was provided. Requirements for patients' informed consent differed. Written informed consent was mandatory at 12, oral at 10 and no form of consent at one hospital. Details such as enough time for consideration, possibility for withdrawal and risks/benefits of participation were provided in 25 to 30% of the institutions. CONCLUSION: There is a considerable variation in the administrative requirements for approval procedures by research ethics committees in Europe. This results in variation of the extent of information and consent procedures for the patients involved

Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): Background, rationale and methodology

Background: Transition from distinct Child and Adolescent Mental Health (CAMHS) to Adult Mental Health Services (AMHS) is beset with multitude of problems affecting continuity of care for young people with mental health needs. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge globally. The overall aim of the Managing the Link and Strengthening Transition from Child to Adult Mental Health Care in Europe (MILESTONE) project (2014-19) is to improve transition from CAMHS to AMHS in diverse healthcare settings across Europe. MILESTONE focuses on current service provision in Europe, new transition-related measures, long term outcomes of young people leaving CAMHS, improving transitional care through 'managed transition', ethics of transitioning and the training of health care professionals. Methods: Data will be collected via systematic literature reviews, pan-European surveys, and focus groups with service providers, users and carers, and members of youth advocacy and mental health advocacy groups. A prospective cohort study will be conducted with a nested cluster randomised controlled trial in eight European Union (EU) countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS users, their carers, and clinicians. Discussion: Improving transitional care can facilitate not only recovery but also mental health promotion and mental illness prevention for young people. MILESTONE will provide evidence of the organisational structures and processes influencing transition at the service interface across differing healthcare models in Europe and longitudinal outcomes for young people leaving CAMHS, solutions for improving transitional care in a cost-effective manner, training modules for clinicians, and commissioning and policy guidelines for service providers and policy makers

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially