Nejčastěji používané přístupy ve druhé a třetí linii léčby mnohočetného myelomu (MM) jsou v České republice režimy založené na bortezomibu a lenalidomidu (VD, CVD, VTD, RD). Nyní byla schválena kombinace carfilzomibu (Kyprolis) s lenalidomidem (Revlimid) a dexamethasonem (KRd) v léčbě relapsu MM. Schválení podpořily výsledky randomizované studie ASPIRE fáze III, v níž byly srovnávány výsledky léčby pacientů s relapsem MM kombinací KRd oproti Rd, a to s jednou až třemi předchozími léčebnými liniemi. Kombinace KRd významně snížila riziko progrese nemoci či úmrtí na MM. Medián přežití bez progrese byl 26,3 měsíce u KRd oproti 17,6 měsíce s dvojkombinací Rd. Medián celkového přežití byl 48,3 měsíce v rameni KRd oproti 40,4 měsíce v rameni Rd. Mezi specifické nežádoucí účinky stupně > 3 patřilo srdeční selhání (4,3 % vs. 2,1 %), ischemická choroba srdeční 3,8 % vs. 2,3 % a arteriální hypertenze (6,4 % vs. 2,3 %).
In the Czech Republic bortezomib and lenalidomide-based regimens (VD, CVD, VTD, RD) are the most commonly used second- and third-line therapies for patients with multiple myeloma (MM). Now is new combination - carfilzomib-lenalidomid-dexamethason (KRd) approved for the treatment for patients with relapse of MM. The approvals for the combination KRd were based on results of randomized ASPIRE trial, phase 3, which evaluated KRd versus Rd in patients with relapsed or refractory MM (1-3 previous lines of therapy). Treatment with KRd led to a significant reduction in the risk of disease progression or death. Progression-free survival was significantly improved with carfilzomib (median 26.3 months for KRd versus 17.6 months for Rd). Median overall survival was 48.3 months for KRd versus 40.4 months for Rd. Selected grade > 3 adverse events of interest included cardiac failure (4.3 % vs 2.1 %), ischemic heart disease (3.8 % vs 2.3 %) and arterial hypertension (6.4 % vs 2.3 %).
- Keywords
- Kyprolis,
- MeSH
- Survival Analysis MeSH
- Dexamethasone administration & dosage MeSH
- Injections, Intravenous MeSH
- Humans MeSH
- Multiple Myeloma * drug therapy pathology MeSH
- Oligopeptides therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Recurrence MeSH
- Thalidomide analogs & derivatives administration & dosage MeSH
- Ubiquitin antagonists & inhibitors MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Randomized Controlled Trial MeSH
- MeSH
- Remission Induction MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Multiple Myeloma * drug therapy MeSH
- Oligopeptides pharmacology MeSH
- Survival MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
OBJECTIVES: Pseudomonas aeruginosa (PA) is a common causative pathogen of pneumonia acquired in the intensive care unit (ICU). The aim of this study was to determine the incidence of PA ICU pneumonia (PAIP) and to quantify its independent association with PA colonization at different body sites. METHODS: Adult patients on mechanical ventilation at ICU admission were prospectively enrolled across 30 European ICUs. PA colonization in the perianal area and in the lower respiratory tract was assessed within 72 hours after ICU admission and twice weekly until ICU discharge. PAIP development was evaluated daily. Competing risk models with colonization as a time-varying exposure and ICU death and discharge as competing events were fitted and adjusted for confounders to investigate the association between PA carriage and PAIP. RESULTS: A total of 1971 subjects were enrolled. The colonization prevalence with PA in the first 72 hours of ICU admission was 10.4% (179 perianal and 51 respiratory), whereas the acquisition incidence during the ICU stay was 7.0% (158 perianal and 47 respiratory). Of the 43 (1.8%) patients who developed PAIP, 11 (25.6%) were PA colonized on admission and 9 (20.9%) acquired colonization before PAIP onset. Both perianal (adjusted subdistribution hazard ratio, 4.4; 95% CI, 1.7-11.6) and respiratory colonization (adjusted subdistribution hazard ratio: 4.6, 95% CI, 1.9-11.1) were independently associated with PAIP development. DISCUSSION: PAIP incidence was higher in PA colonized vs. non-colonized patients. Colonization of both the rectum and of the respiratory tract was associated with development of PAIP. The increased risk of PA colonization for subsequent infection provides an opportunity for targeted preventive interventions.
- MeSH
- Adult MeSH
- Incidence MeSH
- Cross Infection epidemiology microbiology MeSH
- Intensive Care Units * statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Carrier State epidemiology microbiology MeSH
- Prevalence MeSH
- Prospective Studies MeSH
- Pseudomonas Infections * epidemiology microbiology MeSH
- Pseudomonas aeruginosa * isolation & purification MeSH
- Aged MeSH
- Pneumonia, Ventilator-Associated epidemiology microbiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
INTRODUCTION: In the favourable political climate of the mid-2010s, the standards for Assessment & Selection of Prevention programmes Issued from the Review of EDPQS (ASPIRE) were developed to support project planning in drug prevention. METHODS: This case study is a narrative from the main coordinator responsible for drafting this quality assurance material. RESULTS: The framework that led to the creation of the ASPIRE standards is described. The production process is then explained and, thereby, the 12 ASPIRE standards resulting from it are presented. These quality standards and their associated attributes form a coherent quality assessment checklist that provides guidance for needs assessment, theoretical basis, and planned resources. Quality compliance is assessed against a scoring system. Finally, the needs for improvement are discussed, including the dissemination of the standards. CONCLUSIONS: The ASPIRE material has high potential for transferability. However, a promotion strategy and evaluation results are needed to improve the dissemination of such tools and their ownership by prevention stakeholders.
- Keywords
- karfilzomib,
- MeSH
- Survival Analysis MeSH
- Dexamethasone * administration & dosage pharmacokinetics adverse effects therapeutic use MeSH
- Adult MeSH
- Proteasome Inhibitors * administration & dosage pharmacokinetics adverse effects therapeutic use MeSH
- Clinical Trials, Phase III as Topic MeSH
- Drug Therapy, Combination MeSH
- Quality of Life MeSH
- Lenalidomide MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma * drug therapy MeSH
- Randomized Controlled Trials as Topic MeSH
- Recurrence MeSH
- Aged MeSH
- Therapeutic Equivalency MeSH
- Thalidomide * analogs & derivatives administration & dosage pharmacokinetics adverse effects therapeutic use MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Evaluation Study MeSH
Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib-dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR, bortezomib-dexamethasone). This subgroup analysis of ASPIRE and ENDEAVOR evaluated outcomes according to prior ASCT status. In total, 446 patients in ASPIRE and 538 in ENDEAVOR had prior ASCT. Median PFS was longer for carfilzomib-based regimens vs non-carfilzomib-based regimens for patients with prior ASCT (ASPIRE: 26.3 vs 17.8 months (hazard ratio (HR)=0.68); ENDEAVOR: not estimable vs 10.2 months (HR=0.61)), those with one prior line of therapy that included ASCT (ASPIRE: 29.7 vs 17.8 months (HR=0.70); ENDEAVOR: not estimable vs 11.2 months (HR=0.46)), and those without prior ASCT (ASPIRE: 26.4 vs 16.6 months (HR=0.76); ENDEAVOR: 17.7 vs 8.5 months (HR=0.43)). Overall response rates also favored the carfilzomib-based regimens. No new safety signals were detected. This analysis suggests that carfilzomib-based treatment may lead to improvement in PFS and response rates regardless of prior transplant status. Further evaluation is warranted.
- MeSH
- Transplantation, Autologous MeSH
- Adult MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma drug therapy mortality pathology therapy MeSH
- Oligopeptides administration & dosage MeSH
- Retreatment MeSH
- Postoperative Care MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Recurrence MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Hematopoietic Stem Cell Transplantation MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
IMPORTANCE: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. OBJECTIVES: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio. EXPOSURE: Preoperative S aureus colonization. MAIN OUTCOMES AND MEASURES: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models. RESULTS: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs. CONCLUSIONS AND RELEVANCE: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.
- MeSH
- Surgical Wound Infection prevention & control MeSH
- Cohort Studies MeSH
- Humans MeSH
- Mastectomy MeSH
- Breast Neoplasms * complications MeSH
- Aged MeSH
- Staphylococcal Infections * prevention & control MeSH
- Staphylococcus aureus MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- MeSH
- Survival Analysis MeSH
- Bortezomib administration & dosage MeSH
- Dexamethasone administration & dosage MeSH
- Adult MeSH
- Humans MeSH
- Neoplasm Recurrence, Local drug therapy MeSH
- Multiple Myeloma * drug therapy mortality pathology MeSH
- Oligopeptides administration & dosage pharmacology MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
