Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33764408

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder known for its broad clinical spectrum. Recently, the European, British and Latin American rheumatology professional societies (EULAR, BSR and PANLAR) published updated recommendations for SLE management. The objective of this study was to characterize the data supporting the updated recommendations, with the goal of highlighting areas which could benefit from additional high-quality research. METHODS: References were compiled from the recently published EULAR, BSR and PANLAR SLE treatment recommendations. Data collected from each study included publication year, treatment regimen, study design, sample size, inclusion and exclusion criteria and relevant SLE diagnostic criteria. Studies with less than 10 patients and those which did not specify the SLE diagnostic criteria used were excluded. RESULTS: Altogether 250 studies were included in this study. The majority were prospective and retrospective cohorts (72%), with only a small percentage of randomized controlled trials (28%). The median number of patients included was 37 (IQR 19-86). The revised American College of Rheumatology (ACR) 1982 criteria were the most commonly used criteria for SLE diagnosis (52%), followed by the revised ACR criteria from 1997 (27%). Only a small proportion of studies included the use of disease activity scores when defining study population (15%). CONCLUSIONS: Our study has indicated a scarcity of sufficiently powered high-quality research referenced in the recently published SLE treatment guidelines. Well-designed large-scale studies utilizing the updated 2019 SLE diagnostic criteria are needed to better inform healthcare professionals caring for patients with SLE.

2.
J Natl Cancer Inst ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616650

RESUMO

BACKGROUND: Clinician reporting of symptomatic adverse events (AEs) in phase I trials utilizes the Common Terminology Criteria for Adverse Events (CTCAE). The utility of the patient-reported outcomes (PRO) version of the CTCAE (PRO-CTCAE) in this setting is unknown. This prospective, observational study compared patient- and clinician-reported symptomatic-AEs in phase I patients. METHODS: Phase I study eligible patients at Princess Margaret were surveyed with the PRO-CTCAE full item library (78 symptomatic-AEs) at baseline (BL), mid-cycle 1 (C1) and mid-cycle 2 (C2). Patient and trial characteristics, best response, and survival data were collected. Presence/absence of patient- (PRO-CTCAE) or clinician-reported (CTCAEv4) symptomatic-AEs were compared (kappa) at defined timepoints and overall (BL+C1+C2). RESULTS: Of 292 patients approached from 05/2017-01/2019, 265 (90.8%) were consented, with 243 (91.7%) evaluable and 552 PRO-CTCAE surveys (completion rate = 98.7%) included in analyses. Evaluation of overall patient-reported symptomatic-AEs identified 50 PRO-CTCAE and 11 CTCAE items with ≥10% reporting frequency. 19 CTCAE items were reported at ≤ 1% despite matched PRO-CTCAE items with reporting ≥10%. Underreported categories included sexual health, bodily emissions, and cognition. Clinician- relative to patient-reporting frequency (ratio) demonstrated 9 symptomatic-AEs with a ≥ 50-fold lower clinician reporting rate. Overall patient-clinician agreement for individual symptomatic-AEs ranged from poor (kappa = 0.00-0.19) to moderate (kappa = 0.40-0.59) with discordance driven by lack of clinician reporting. Dyspnea (kappa = 0.54) and peripheral neuropathy (kappa = 0.63) at BL, and limb edema (kappa = 0.55) at C2 demonstrated highest patient-clinician agreement. CONCLUSION: Poor to moderate patient-clinician agreement for symptomatic-AEs suggests clinician underreporting in phase I trials. Analyses of severity and interference PRO categories are ongoing.

3.
Infect Dis Ther ; 10(1): 621-630, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33594649

RESUMO

INTRODUCTION: Guidelines for treatment of multidrug-resistant (MDR) bacteria rely on newly approved antibiotics, with limited evidence of their effectiveness for treating these infections. Data regarding cost of such an approach are lacking. We aimed to evaluate estimated cost of using newly approved antibiotic drugs compared to older antibiotics for the treatment of difficult-to-treat pathogens. METHODS: MDR bacteria of interest included those defined by the World Health Organization as critical or of high priority for research. Old and newly approved antibiotics for these bacteria, defined as approved before or after January 2010, respectively, were evaluated for treatment cost and for 14-day treatment course. Estimated annual costs were calculated based on the Centers for Disease Control and Prevention's' report on MDR bacteria prevalence in US hospitalized patients. Old and new drugs costs were compared. RESULTS: The cost of a 14-day treatment course for methicillin-resistant Staphylococcus aureus bacteremia with a newly approved drug was found to be 6 to 60 times higher than that of older drugs. Similarly, the cost of a 14-day course for carbapenem-resistant Enterobacterales or MDR Pseudomonas aeruginosa was doubled with new drugs; and for carbapenem-resistant Acinetobacter baumannii, ~ 20 times higher with newer drugs. Annual incremental costs of treating difficult-to-treat Gram-negative bacteria with new drugs ranged from 30 million to over 500 million USD. CONCLUSIONS: Using newly approved antibiotic drugs for MDR infections carries a large incremental cost. Additional data to support survival benefit of these drugs are required to justify the price differences. Subgroups of patients who would benefit most from treatment should be defined.

4.
Lung Cancer ; 152: 58-65, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33352384

RESUMO

INTRODUCTION: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). METHODS: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. RESULTS: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; pinteraction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (pinteraction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (pinteraction<0.001) and obese categories (pinteraction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers. CONCLUSION: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.

5.
Hum Vaccin Immunother ; : 1-4, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270474

RESUMO

Vaccines have changed modern medicine, and are a mainstay in reducing morbidity and mortality from infections. Our research group recently published a study in which we found that vaccines approved by the US Food and Drugs Administration were safe with few clinically important post-approval adverse effects. The current COVID-19 pandemic presents regulators with the unprecedented challenge of balancing a public demand for the rapid development and approval of a safe and effective SARS-CoV-2 vaccine without compromising the strict pre-marketing requirements used for previous vaccines. Here, we review the approval process and safety profiles of FDA approved vaccines and discuss some of the challenges currently facing the FDA regarding the SARS-CoV-2 vaccine approval.

6.
Cancer Treat Rev ; 91: 102113, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33128993

RESUMO

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines can include recommendations for off-label use of anti-cancer drugs. Here, we evaluate NCCN recommendations not supported by US Food and Drug Administration (FDA) approval and explore associations with such recommendations. METHODS: All NCCN recommendations for MBC and their supporting data were identified. Drug labels were reviewed to determine whether recommendations are FDA approved. Logistic regression was used to compare FDA approved and off-label recommendations for pre-specified categories, including drug type, tumor subtype, level of recommendation and line of therapy. RESULTS: Of 124 recommendations identified, 68 (55%) were off-label. Chemotherapy and human epidermal growth factor receptor 2 (HER2) targeted drugs were associated with lower odds of FDA approval (OR = 0.28, p = 0.001 and OR = 0.29, 95% p = 0.005, respectively). Recommendations for endocrine therapy (OR = 3.44, p = 0.009) and non-HER2 targeted treatment (OR = 10.0, p < 0.001) were more commonly FDA approved indications. Compared to combination therapies, monotherapies were more likely to be FDA approved (OR = 3.45, p = 0.001) as were category 1 (OR = 7.63, p = 0.001) and preferred NCCN recommendations (OR = 4.07, p < 0.001). Compared to off-label recommendations, NCCN recommendations of approved drugs were based on significantly higher sample size (mean 477 vs. 342 patients, p = 0.02) and were non-significantly associated with availability of randomized data (OR = 2.0, 95% CI 0.89-4.49, p = 0.09). CONCLUSION: More than half of all NCCN recommendations for MBC are off-label, mostly involving chemotherapy containing regimes for HER2 negative disease and combinations which include HER2-targeted drugs. Improved transparency of NCCN guidelines may result from reporting of the strength of the evidence supporting recommendations for MBC.

7.
JAMA Intern Med ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32986074

RESUMO

Importance: Medical Device Safety Communications (MDSCs) are used by the US Food and Drug Administration (FDA) to convey important new safety information to patients and health care professionals. The sources of initial safety signals that trigger MDSCs have not been described previously. Objective: To assess the sources of initial safety signals that trigger publication of MDSCs and the potential associations among MDSC data source, type of safety issue, and subsequent FDA action. Design, Setting, and Participants: In this cross-sectional study, all MDSCs published on the FDA website between January 1, 2011, and December 31, 2019, were assessed. The MDSC characteristics, sources of initiating safety signals, regulatory approval or clearance pathways of the related medical devices, and subsequent FDA actions were collected from the FDA website. Main Outcomes and Measures: The main outcome was the distribution of sources of initial safety signals that led to publication of MDSCs. Secondary aims included exploration of potential associations among safety signal sources (direct reporting vs other), type of safety issue (death vs other), and FDA action (withdrawal vs other). Results: A total of 93 MDSCs were evaluated. Median time from device approval to MDSC posting was 10 years (interquartile range, 6-16 years). The most common data sources that triggered MDSCs were direct reports to the FDA through the Medical Device Reporting (MDR) program (44 of 93 [47%]) followed by regulator-initiated assessments (32 [34%]). Common safety issues included patient injury (25 [27%]), potential wrong diagnoses (19 [20%]), and death (18 [19%]). Frequent FDA action after MDSC posting included recommendation for increased vigilance and caution (47 [51%]), complete device withdrawal (12 [13%]), and warnings of specific lots or clinics (12 [13%]). There was a statistically significant correlation between direct reports of adverse events to the FDA through the MDR program and risk of death as a safety issue (14 of 44 [32%] for direct reporting vs 4 of 49 [8%] for any other data sources, P = .007). Conclusions and Relevance: In this cross-sectional study, the most common source of initial safety signals that triggered MDSCs was direct reports of real-world adverse events to the FDA through the MDR program. The delayed detection of postmarketing adverse events highlights the importance of proactive identification of emerging device-related safety issues.

8.
Ann Intern Med ; 173(6): 445-449, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32716700

RESUMO

BACKGROUND: Vaccines are one of the greatest achievements in public health. Prevalence and clinical significance of emerging postapproval, vaccine-related safety issues have not been systematically studied. OBJECTIVE: To explore postmarketing safety modifications in U.S. Food and Drug Administration (FDA)-approved vaccine labels. DESIGN: Retrospective cohort study. SETTING: United States. PARTICIPANTS: Initial and subsequent labels of all vaccines that were FDA-approved between 1 January 1996 and 31 December 2015. MEASUREMENTS: The primary aim was a descriptive analysis of the prevalence and characteristics of postapproval, safety-related label changes. The secondary aim was to describe the distribution of data sources triggering these modifications. RESULTS: The study cohort comprised 57 FDA-approved vaccines. Initial approval for 53 (93%) of the vaccines was supported by randomized controlled trials, with a median cohort size of 4161 participants (interquartile range, 2204 to 8634 participants). There were 58 postapproval, safety-related label modifications associated with 25 vaccines (49 warnings and precautions, 8 contraindications, and 1 safety-related withdrawal). The initial approval trial characteristics were similar in vaccines with and without postmarketing, safety-related label modifications. The most common safety issue triggering label modifications was expansion of population restrictions (n = 21 [36%]), followed by allergies (n = 13 [22%]). The most common source of safety data was postmarketing surveillance (n = 28 of 58 [48%]). LIMITATION: The data source of the initial signal triggering safety-related label changes may not necessarily represent all safety data received and processed by the FDA. CONCLUSION: Over a 20-year period, vaccines were found to be remarkably safe. A large proportion of safety issues were identified through existing postmarketing surveillance programs and were of limited clinical significance. These findings confirm the robustness of the vaccine approval system and postmarketing surveillance. PRIMARY FUNDING SOURCE: None.

10.
Am J Cardiol ; 130: 56-63, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32680674

RESUMO

In light of recent studies describing the antibacterial properties of ticagrelor, the association between treatment with ticagrelor and subsequent risk for infection following acute coronary syndrome (ACS) is taking on increased importance. A single center, retrospective, matched cohort analysis was performed. All patients older than 30 years of age admitted between January 1, 2013 and November 1, 2019 for an ACS and discharged with dual antiplatelet therapy (DAPT) were included. The primary outcome was defined as hospital admissions due to infections likely caused by gram-positive bacteria up to 1 year following the ACS hospitalization. The base cohort included 3,909 patients. About 2,035 (52.1%) were treated with ticagrelor and 1,874 (47.9%) with clopidogrel. Patients treated with ticagrelor had a 64% lower risk of gram-positive infection during the first year following hospitalization after adjusting for demographic and co-morbidity factors compared with those treated with clopidogrel (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21 to 0.61; p <0.001). In a cohort starting from 1 year (conclusion of DAPT period) and up to 3 years following ACS hospitalization, the risk of gram-positive infection was comparable in both groups (HR, 0.70; 95% CI, 0.41 to 1.19; p = 0.182). Treatment with ticagrelor was not associated with a reduced risk of gram-negative infections (HR, 0.48; 95% CI, 0.21 to 1.06; p = 0.07). In conclusion, DAPT regimen that includes aspirin and ticagrelor is associated with reduced risk of gram-positive infection compared with the combination of aspirin and clopidogrel.


Assuntos
Síndrome Coronariana Aguda/complicações , Infecções por Bactérias Gram-Positivas/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/uso terapêutico , Estudos de Coortes , Feminino , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco
11.
Hematol Oncol ; 38(4): 584-588, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32506594

RESUMO

High dose methotrexate (HDMTX)-induced acute kidney injury (AKI) is a well-known adverse event in hemato-oncology patients. Our purpose was to define factors and setup cut-offs that may help better identify patients at-risk for developing AKI following HDMTX. All consecutive patients who received MTX dose ≥1 g were retrospectively reviewed. We compared patients with or without renal toxicity. We used a logistic regression model to define baseline variables associated with AKI. Overall survival (OS) was estimated by the Kaplan-Meier method employing log-rank test. Between 2012 and 2017, 160 patients were included with a total of 265 courses. Indications included: primary central nervous system (CNS) lymphoma, CNS prophylaxis in other lymphoma types, acute lymphatic leukemia and others. Median age at diagnosis was 58 years (range, 18-84), 54% were males, median MTX dose was 1941 mg/m2 (range, 743-5442) and AKI developed in 9% of drug administrations (n = 24). In univariate analysis: age > 40, LDH > 380 units/L, eGFR < 112 mL/min, albumin <3.6 mg/dL at baseline and Charlson comorbidity index (CCI) were associated with AKI. In multivariable analysis, only LDH > 380 units/L (OR = 4.1, 95% confidence interval [CI] 1.04-20.9, P = .04) and albumin levels <3.6 g/dL (OR = 4.17, 95% CI 1.04-6.5, P = .04) remained significant. In patients with AKI, median drug elimination was longer (8 days vs 5 days). In 80% of cases, the creatinine levels returned to normal within 1 month. Yet, the median survival of patients who developed AKI was 37 months, compared to 145 months in patients without AKI (Log rank = 0.015). In conclusion, LDH > 380 units/L and albumin <3.6 g/dL were the strongest factors associated with AKI in patients receiving HDMTX. Although the rise in creatinine levels was almost uniformly reversible, AKI was associated with increased mortality rates.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Antimetabólitos Antineoplásicos/efeitos adversos , Neoplasias Hematológicas/tratamento farmacológico , Metotrexato/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
12.
Intern Emerg Med ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372331

RESUMO

Acute hepatic porphyria (AHP) attacks begin with abdominal pain and can progress to severe life-threatening conditions. Early diagnosis and treatment may prevent these complications. We investigated the difference between the severity of porphyria attacks before and after porphyria diagnosis. A retrospective study including AHP patients hospitalized for an acute attack in Israel during a 15-year period. Diagnosis of an attack was based on typical clinical symptoms accompanied by at least one documented elevated urinary porphobilinogen above fourfold of normal values. The primary outcome was intensive care unit (ICU) admissions. Secondary outcomes included the length of hospital stay, severe hyponatremia, seizures, and psychiatric symptoms. 42 attacks in 9 patients were included. Most attacks occurred in women (78.6%) and in acute intermittent porphyria patients (76.2%). The mean age of attack was 26.5 (± 6.3) years. Attacks following porphyria diagnosis had a lower prevalence of ICU admission (3.3% versus 75.0%, p < 0.001), seizures (0% versus 50.0%, p < 0.001), psychiatric symptoms (23.3% versus 66.7%, p = 0.01), severe hyponatremia (16.7% versus 83.3%, p < 0.001), and median length of hospital stay (5 versus 11.0 days, p < 0.001). These results remained significant after simple univariate logistic regression for ICU admission [odds ratio (OR) 0.01, 95% confidence interval (CI) 0.00-0.12], prolonged hospital stay (OR 0.08, 95% CI 0.01-0.41), seizures or neurological symptoms (OR 0.06, 95% CI 0.01-0.30), and severe hyponatremia (OR 0.02, 95% CI 0.00-0.20). Previously diagnosed AHP patients have a significantly milder attack course as compared to previously undiagnosed patients. Family screening following sentinel cases might prevent severe AHP attacks.

13.
Isr Med Assoc J ; 22(5): 279-284, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32378818

RESUMO

BACKGROUND: Recent data regarding polymicrobial bacteremia (PMB) are lacking. OBJECTIVES: To characterize risk factors as well as clinical, microbiological, and prognostic patterns of patients with PMB in a modern hospital setting. METHODS: A single center retrospective study including all patients diagnosed with PMB during 2013 was conducted. PMB was defined as two or more organisms cultured from the blood of the same patient within 72 hours. Patients with monomicrobial infections served as controls. RESULTS: There were 135 episodes (2% of all bacteremia episodes) of true PMB among 123 patients during the study period. Recent invasive procedures (odds ratio [OR] 3.59, 95% confidence interval [95%CI] 1.41-9.12, P = 0.006) and foreign bodies (OR 1.88, 95%CI 1.06-3.33, P = 0.04) were risk factors for PMB when compared with 79 patients with monomicrobial bacteremia. Central-line-associated infections were the most common infection source among patients with PMB (n=34, 28%). Enterobacteriaceae were the most commonly implicated pathogen (n=95, 77%). Non-fermenting Gram-negative bacilli were significantly more common than previously reported (n=55, 45%). Although crude 30-day mortality was higher (48% vs. 33%) in PMB patients, adjusted mortality was comparable in the two groups. CONCLUSIONS: PMB rate in our cohort was considerably lower than in previous reports. Central-line-associated infections were more common than classic PMB sources. Mortality remained high. Strategies for early identification and better care for these patients should be pursued.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/etiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
14.
Leuk Lymphoma ; 61(9): 2216-2220, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32449397

RESUMO

Changes in primary outcome and sample size measures after onset of patient accrual affects the scientific basis of evidence-based medicine. The FDA website was searched for trials supporting new hemato-oncology drug approvals from January 2010 to December 2017. Matching ClinicalTrials.gov entries were compared to identify modifications. Associated publications were reviewed for reporting of these changes. Of 69 included trials, five (7%) had post accrual modifications in primary outcome and 30 (43%) had modifications in planned sample size. Sample size was increased in 24 trials (median 66 patients, IQR 35-95, median relative increase of 40% from initial sample size) and was decreased in 6 trials (median 38 patients, IQR 27-60, median relative decrease of 25%). None of the primary outcome modifications and only 53% of the sample size modifications were reported in the related publications. Further improvement is warranted in order to achieve complete transparency in reporting landmark studies.

16.
Clin Infect Dis ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32337578

RESUMO

BACKGROUND: Infections caused by multidrug resistant (MDR) bacteria are major public health threat. We aimed to assess the data supporting US Food and Drug (FDA) approval of new agents aimed to treat MDR bacterial infections, and the data provided by post-marketing studies. METHODS: We identified all drugs with in-vitro activity against MDR bacteria initially approved by FDA between January 2010- December 2018. Characteristics of trials supporting approval and regulatory pathways were collected from Drugs@FDA. Characteristics of post-marketing studies were extracted from drug labels and ClinicalTrials.gov entries effective on June 1, 2019. RESULTS: Initial approval of 11 newly approved antibiotics with anti-MDR activity was supported by 20 trials, all with non-inferiority design. All initially approved indications were for common infections, mostly acute bacterial skin and skin-structure infections, regardless of causative microorganism. The proportion of MDR bacteria in most trials was low (<10% for Gram-negative infections, <1% for Gram-positive pneumonia). Most trials (90%) excluded immunocompromised and critically ill patients. Of 16 additional post-marketing randomized controlled trials identified through ClinicalTrials.gov, only 2 exclusively included infections caused by MDR bacteria, comprising 116 patients. No drug was granted accelerated approval, which would mandate post-marketing efficacy studies. CONCLUSIONS: The approval of new drugs with potential clinical activity against MDR bacteria is supported by trials evaluating infections caused by non-MDR organisms, using non-inferiority design and excluding the patients most likely to require these agents. Subsequent post-marketing efficacy data against these organisms are scarce. Healthcare professionals and regulators should demand more robust data to support clinical decision making.

17.
J Clin Endocrinol Metab ; 105(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899506

RESUMO

CONTEXT: Denosumab inhibits the receptor activator of nuclear factor κ-Β ligand, an immune system modulator. Safety endpoints including risk for infections were assessed as secondary outcomes in randomized controlled trials (RCTs) of the drug. OBJECTIVE: To assess the risk of serious adverse events of infections (SAEI) in denosumab-treated patients. DATA SOURCES: PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019. STUDY SELECTION: All RCTs of denosumab (60 mg every 6 months) versus any comparator were included. We excluded trials in cancer patients for prevention of skeletal-related events. DATA EXTRACTION: Two reviewers independently applied selection criteria and extracted the data. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a fixed effect model. Sensitivity analysis was based on risk of bias. DATA SYNTHESIS: Thirty-three studies (22 253 patients) were included. There was a higher incidence of SAEI during denosumab treatment versus any comparator (RR, 1.21; 95% CI, 1.04-1.40; I2 = 0%), mainly of ear, nose, and throat (RR, 2.66; 95% CI, 1.20-5.91) and gastrointestinal origin (RR, 1.43; 95% CI, 1.02-2.01). RR was similar in a sensitivity analysis based on adequate allocation concealment. The RR of any infection (RR, 1.03; 95% CI, 0.99-1.06) and infection-related mortality (RR, 0.50; 95% CI, 0.20-1.23) was comparable between groups. CONCLUSIONS: A higher incidence of SAEI is demonstrated during treatment with denosumab in an osteoporosis dose. Nevertheless, the overall risk for any infection or related mortality is similar to comparator groups. These findings merit consideration before therapy initiation.

18.
Acta Haematol ; 143(5): 446-451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31752009

RESUMO

INTRODUCTION: A restrictive transfusion strategy of packed red blood cells (PRBCs) has been associated with at least non-inferior patient outcomes in a variety of clinical settings. In December 2014, we conducted an educational intervention which consisted of an oral presentation and computerized notifications at a single tertiary medical center. OBJECTIVE: The aim of this study was to examine the long-term effects of a simple and low-cost educational intervention aimed to promote awareness to transfusion guidelines. METHODS: We retrospectively analyzed all PRBC transfusions ordered between 2014 and 2017. The primary end point was defined as the percentage of PRBC transfused to patients with hemoglobin (Hb) ≥8 g/dL. RESULTS: Between 2014 and 2017, a total of 27,475 PRBCs were transfused in our medical center. There was a continuous reduction in the percentage of PRBCs transfused at a Hb level ≥8 g/dL between 2014 and 2017, with a matching increase in the PRBC percentage trans-fused at Hb <7 g/dL (OR reduction of 42%, 95% CI 0.54-0.62 and OR increase of 68% [95% CI 1.56-1.81], respec-tively). CONCLUSION: A simple educational intervention likely contributed to sustained improvement in the appropriateness of PRBC transfusions.


Assuntos
Transfusão de Eritrócitos/estatística & dados numéricos , Seguimentos , Hemoglobinas/análise , Hospitais , Humanos , Razão de Chances , Estudos Retrospectivos
19.
Semin Arthritis Rheum ; 50(3): 534-545, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31812351

RESUMO

OBJECTIVE: To amass all available evidence from randomized controlled trials regarding the safety of pulse corticosteroids therapy, in order to establish its safety. PATIENTS AND METHODS: All electronic databases from 1/1966 up to 02/2019 were reviewed to find all randomized controlled trials comparing pulse corticosteroids to oral corticosteroids or to placebo/no treatment. Two reviewers independently extracted and recorded data regarding type of corticosteroid treatment, dosages, length of treatment and follow-up. Risk ratios (RR) with 95% (CI) for differences between pulse corticosteroids and comparator were pooled using a fixed effect meta-analysis. The primary outcome was occurrence of severe adverse events (SAEs). Secondary outcomes included any adverse events (AEs), AEs requiring discontinuation, AEs per system involved and all-cause mortality. RESULTS: A total of 64 trials were included: 18 trials which compared pulse corticosteroids to oral corticosteroids and 46 trials which compared pulse corticosteroids to placebo/no intervention. Pulse corticosteroids was not associated with increased risk for SAEs for both comparators: RR 0.77 (95% CI 0.52-1.14), and RR 0.99 (95% CI 0.93-1.06), respectively. Sensitivity analysis based on adequate allocation concealment and use of a valid AE grading did not alter the results. Subgroup analysis revealed no increased risk of specific SAEs or AEs with pulse corticosteroids compared to oral corticosteroids. CONCLUSION: Pulse corticosteroids was not associated with an increase risk of SAEs and should be regarded as safe.

20.
Eur J Intern Med ; 71: 45-49, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31439377

RESUMO

BACKGROUND: Modifications of primary outcome measures after trial initiation can undermine their scientific validity. We aimed to quantify these changes and to characterize potential predictors in clinical drug trials published in high impact factor general medicine journals. METHODS: The study cohort included all prospective, adult drug clinical trials published in the New England Journal of Medicine, JAMA and Lancet between June 2017 and May 2018. The matching ClinicalTrials.gov entries effective at trial initiation were compared with those effective on July 2018, thereby identifying amendments to primary outcome definitions and assessment timeframes and the planned sample size (defined as >10% change). The primary publications were reviewed for reporting of these amendments. Associations between identified changes and trial characteristics were explored using logistic regression. RESULTS: Of the 147 included trials, modifications to primary outcome measures were identified in 80 (54%). Primary outcome definitions, outcome assessment timeframes and the planned sample size were modified in 28 (19%), 12 (8%) and 65 (45%) of registry entries, respectively; of which 21 (75%), 11 (92%), and 33 (51%), respectively, were not reported in the related publications. There were no significant associations between modifications in registry entries and study characteristics. CONCLUSIONS: Approximately half of trials published in influential medical journals present changes to the design while patient accrual is ongoing, and two thirds of them are unreported. Justification for such modifications should be reported more clearly. Reviewers, editors and readers should consult ClinicalTrials.gov for a more comprehensive report of the evolution of key study methods.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...