U praonicama bolničkog rublja vrlo je važno uz dobar učinak pranja postići i zadovoljavajući dezinfekcijski učinak, zbog pristutnosti U mnogih vrsta patogenih organizama. Iako je najvažnije postići ...dezinfekcijski učinak u procesu pranja, potrebno je održavati razinu higijene u dijelovima praonice gdje se tretira čisto i dezinficirano rublje. To je potrebno radi sprječavanja ponovne kontaminacije s patogenim mikroorganizmima iz okoline, poglavito prilikom rukovanja tekstilijama u procesima kao što su glačanje, slaganje, pakiranje i sl. U ovom je radu istražena razina higijene u praonicama bolničkog rublja u Sloveniji i Danskoj, kao i razina higijene tekstilija iz prehrambene industrije u Sloveniji i Norveškoj. Razina higijene opranih tekstilija u Sloveniji ispituje se prema njemačkom RAL-GZ 992, sustavu kontrole kvalitete koji se temelji na preporukama Robert Koch Instituta, europskom standardu RABC i HACCP-načelima. Za danske praonice rublja određuju se ukupni broj bakterija i broj enterobakterija na kritičnim kontrolnim točkama, a stupanj higijene u Norveškoj se određuje na temelju broja aerobnih bakterija, broja koliformih bakterija i broja E. coli na kritičnim točkama. Rezultati istraživanja pokazali su da je primjena stručnih mjera čišćenja i dezinfekcije od osoblja u praonici je najznačajnija u postizanju zadovoljavajuće higijene i da je dezinfekcijski učinak u procesu pranja preliminarni uvjet za dezinficirane tekstilije.
Evinacumab for Homozygous Familial Hypercholesterolemia Raal, Frederick J; Rosenson, Robert S; Reeskamp, Laurens F ...
New England journal of medicine/The New England journal of medicine,
08/2020, Letnik:
383, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is ...associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (
) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia.
In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24.
The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval CI, -65.0 to -33.1; P<0.001); the between-group least-squares mean absolute difference in the LDL cholesterol level was -132.1 mg per deciliter (95% CI, -175.3 to -88.9; P<0.001). The LDL cholesterol level was lower in the evinacumab group than in the placebo group in patients with null-null variants (-43.4% vs. +16.2%) and in those with non-null variants (-49.1% vs. -3.8%). Adverse events were similar in the two groups.
In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks. (Funded by Regeneron Pharmaceuticals; ELIPSE HoFH ClinicalTrials.gov number, NCT03399786.).
Children with severe atopic dermatitis (AD) have limited treatment options.
We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD ...inadequately controlled with topical therapies.
In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS.
Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS.
Short-term 16-week treatment period; severe AD only.
Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL.
Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.
In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized ...patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients.
Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log
copies per milliliter (95% confidence interval CI, -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log
copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody-negative at baseline, the corresponding percentages were 15% and 6% (difference, -9 percentage points; 95% CI, -29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group.
In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.).
There is a great unmet need for advanced therapies that provide rapid, robust, and sustained disease control for patients with ulcerative colitis. We assessed the efficacy and safety of upadacitinib, ...an oral selective Janus kinase 1 inhibitor, as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.
This phase 3, multicentre, randomised, double-blind, placebo-controlled clinical programme consisted of two replicate induction studies (U-ACHIEVE induction UC1 and U-ACCOMPLISH UC2) and a single maintenance study (U-ACHIEVE maintenance UC3). The studies were conducted across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 199 clinical centres in 39 countries (UC1), 204 clinical centres in 40 countries (UC2), and 195 clinical centres in 35 countries (UC3). Patients aged 16–75 years with moderately to severely active ulcerative colitis (Adapted Mayo score 5–9; endoscopic subscore 2 or 3) for at least 90 days were randomly assigned (2:1) to oral upadacitinib 45 mg once daily or placebo for 8 weeks (induction studies). Patients who achieved clinical response following 8-week upadacitinib induction were re-randomly assigned (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks (maintenance study). All patients were randomly assigned using web-based interactive response technology. The primary endpoints were clinical remission per Adapted Mayo score at week 8 (induction) and week 52 (maintenance). The efficacy analyses in the two induction studies were based on the intent-to-treat population, which included all randomised patients who received at least one dose of treatment. In the maintenance study, the primary efficacy analyses reported in this manuscript were based on the first 450 (planned) clinical responders to 8-week induction therapy with upadacitinib 45 mg once daily. The safety analysis population in the induction studies consisted of all randomised patients who received at least one dose of treatment; in the maintenance study, this population included all patients who received at least one dose of treatment as part of the primary analysis population. These studies are registered at ClinicalTrials.gov, NCT02819635 (U-ACHIEVE) and NCT03653026 (U-ACCOMPLISH).
Between Oct 23, 2018, and Sept 7, 2020, 474 patients were randomly assigned to upadacitinib 45 mg once daily (n=319) or placebo (n=155) in UC1. Between Dec 6, 2018, and Jan 14, 2021, 522 patients were randomly assigned to upadacitinib 45 mg once daily (n=345) or placebo (n=177) in UC2. In UC3, a total of 451 patients (21 from the phase 2b study, 278 from UC1, and 152 from UC2) who achieved a clinical response after 8 weeks of upadacitinib induction treatment were randomly assigned again to upadacitinib 15 mg (n=148), upadacitinib 30 mg (n=154), and placebo (n=149) in the primary analysis population. Statistically significantly more patients achieved clinical remission with upadacitinib 45 mg (83 26% of 319 patients in UC1 and 114 34% of 341 patients in UC2) than in the placebo group (seven 5% of 154 patients in UC1 and seven 4% of 174 patients; p<0·0001; adjusted treatment difference 21·6% 95% CI 15·8–27·4 for UC1 and 29·0% 23·2–34·7 for UC2). In the maintenance study, clinical remission was achieved by statistically significantly more patients receiving upadacitinib (15 mg 63 42% of 148; 30 mg 80 52% of 154) than those receiving placebo (18 12% of 149; p<0·0001; adjusted treatment difference 30·7% 21·7–39·8 for upadacitinib 15 mg vs placebo and 39·0% 29·7–48·2 for upadacitinib 30 mg vs placebo). The most commonly reported adverse events in UC1 were nasopharyngitis (15 5% of 319 in the upadacitinib 45 mg group vs six 4% of 155 in the placebo group), creatine phosphokinase elevation (15 4% vs three 2%), and acne (15 5% vs one 1%). In UC2, the most frequently reported adverse event was acne (24 7% of 344 in the upadacitinib 45 mg group vs three 2% of 177 in the placebo group). In both induction studies, serious adverse events and adverse events leading to discontinuation of treatment were less frequent in the upadacitinib 45 mg group than in the placebo group (serious adverse events eight 3% vs nine (6%) in UC1 and 11 3% vs eight 5% in UC2; adverse events leading to discontinuation six 2% vs 14 9% in UC1 and six 2% vs nine 5% in UC2). In UC3, the most frequently reported adverse events (≥5%) were worsening of ulcerative colitis (19 13% of 148 in the upadacitinib 15 mg group vs 11 7% of 154 in the upadacitinib 30 mg group vs 45 30% of 149 in the placebo group), nasopharyngitis (18 12% vs 22 14% vs 15 10%), creatine phosphokinase elevation (nine 6% vs 13 8% vs three 2%), arthralgia (nine 6% vs five 3% vs 15 10%), and upper respiratory tract infection (seven 5% vs nine 6% vs six 4%). The proportion of serious adverse events (ten 7% vs nine 6% vs 19 13%) and adverse events leading to discontinuation (six 4% vs ten 6% vs 17 11%) was lower in both upadacitinib groups than in the placebo group. Events of cancer, adjudicated major adverse cardiac events, or venous thromboembolism were reported infrequently. There were no treatment-related deaths.
Upadacitinib demonstrated a positive efficacy and safety profile and could be an effective treatment option for patients with moderately to severely active ulcerative colitis.
AbbVie.
Prurigo nodularis (PN) is a chronic inflammatory skin disease with intensely pruritic nodules. The LIBERTY-PN PRIME and PRIME2 phase 3 trials enrolled adults with PN with ≥20 nodules and severe itch ...uncontrolled with topical therapies. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. Patients were randomized 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, measured by proportion of patients with a ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included nodule number reduction to ≤5 at week 24. PRIME and PRIME2 enrolled 151 and 160 patients, respectively. Both trials met all the pre-specified primary and key secondary endpoints. A ≥4-point WI-NRS reduction at week 24 in the dupilumab and placebo arms was achieved by 60.0% and 18.4% of patients, respectively, in PRIME (95% confidence interval (CI), 27.8-57.7 for the difference, P < 0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI, 2.3-31.2; P = 0.022). Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions versus placebo in PN. Safety was consistent with the known dupilumab safety profile.ClinicalTrials.gov identifiers: NCT04183335 and NCT04202679 .
Summary Background Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy ...and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis. Methods This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment IGA score 3–4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0–1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434. Findings Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0–1 (23 28% vs three 4%, difference 24% 95% CI 13–34; p<0·0001) and EASI-75 (44 53% vs eight 11%, difference 42% 95% CI 29–55; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 64% of 83 patients) and placebo group (58 74% of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four 5%) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation. Interpretation Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults. Funding Sanofi and Regeneron Pharmaceuticals
To estimate the efficacy and toxicity of AMG 386, an investigational peptide-Fc fusion protein that neutralizes the interaction between the Tie2 receptor and angiopoietin-1/2, plus weekly paclitaxel ...in patients with recurrent ovarian cancer.
Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned 1:1:1 to receive paclitaxel (80 mg/m(2) once weekly QW, 3 weeks on/1 week off) plus intravenous AMG 386 10 mg/kg QW (arm A), AMG 386 3 mg/kg QW (arm B), or placebo QW (arm C). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response, CA-125 response, safety, and pharmacokinetics.
One hundred sixty-one patients were randomly assigned. Median PFS was 7.2 months (95% CI, 5.3 to 8.1 months) in arm A, 5.7 months (95% CI, 4.6 to 8.0 months) in arm B, and 4.6 months (95% CI, 1.9 to 6.7 months) in arm C. The hazard ratio for arms A and B combined versus arm C was 0.76 (95% CI, 0.52 to 1.12; P = .165). Further analyses suggested an exploratory dose-response effect for PFS across arms (Tarone's test, P = .037). Objective response rates for arms A, B, and C were 37%, 19%, and 27%, respectively. The incidence of grade ≥ 3 adverse events (AEs) in arms A, B, and C was 65%, 55%, and 64%, respectively. Frequent AEs included hypertension (8%, 6%, and 5% in arms A, B, and C, respectively), peripheral edema (71%, 51%, and 22% in arms A, B, and C, respectively), and hypokalemia (21%, 15%, and 5% in arms A, B, and C, respectively). AMG 386 exhibited linear pharmacokinetic properties at the tested doses.
AMG 386 combined with weekly paclitaxel was tolerable, with a manageable and distinct toxicity profile. The data suggest evidence of antitumor activity and a dose-response effect, warranting further studies in ovarian cancer.
The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD).
In this phase 1/2/3, double-blind, ...placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus.
In total, 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% confidence interval CI, -.51 to -.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2%-74.0%). No safety concerns were noted.
In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients.
NCT04426695.
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