Search

Purpose: The Pediatric Research Equity Act (PREA) gives the US Food and Drug Administration (FDA) authority to require pediatric studies for drug and biologics products under certain circumstances and to waive this requirement in some, or all, pediatric ages. When studies are waived for safety, PREA stipulates the safety issue must be described in labeling. This study assessed the rate of including waiver-related safety information in labeling. Methods: FDA databases were reviewed to determine the number of safety-related pediatric study waivers and issued from December 2003 through August 2020, and corresponding labeling to establish when relevant safety information was included. Descriptive comparisons were conducted across Cohort 1: December 2003–2007, Cohort 2: 2008–2011, Cohort 3: 2012–2015, and Cohort 4: 2016-August 2020. Results: One hundred sixteen safety waivers were issued [Cohort 1 (n = 1); Cohort 2 (n = 38), Cohort 3 (n = 37), and Cohort 4 (n = 40)] for 84 unique drugs or biologics. Most (106 of 116; 91%) waiver-related safety issues were described in labeling [Cohort 1 (1 of 1), Cohort 2 (33 of 38), Cohort 3 (33 of 37), and Cohort 4 (39 of 40)]. Safety waivers were most common in patients ≤ 17 years (n = 40) and least common in patients ≤ 6 months (n = 15). Products for infections (n = 32) were the most common group receiving safety waivers; 17 for non-antiviral anti-infective products including treatments for dermatologic infestations/infections, and 15 for antiviral products. Conclusion: The data confirm that FDA consistently describes waiver-related safety information in drug/biologic product labeling since the inception of PREA in December of 2003. [ABSTRACT FROM AUTHOR]

Background: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) began collaboration on Good Clinical Practice (GCP) inspections for marketing applications since 2009. The main characteristics of the GCP inspection processes between FDA and EMA were never evaluated. This is the first analysis comparing the GCP inspection processes between the two agencies. Methods: We examined and analyzed the key characteristics of the GCP inspection processes, including the geographical distribution, inspection types and timelines from application submission to final inspection reporting for marketing applications from September 2009 through December 2015. Results: Fifty-five shared applications were included for analysis. For these applications, a total of 433 GCP inspections were conducted in 47 countries. Most clinical investigator (CI) inspections were conducted in regions outside of each agency's own regulatory jurisdiction, while most sponsor/contract research organization (CRO) inspections were conducted in the U.S. by both agencies. Twenty-eight shared applications included common sites inspected by both agencies. There were 15 joint inspections conducted for seven of these applications and the remaining applications had common sites inspected by both agencies at separate times. Of the joint inspections, 73% were conducted in the U.S and 20% in the E.U. The median time from submission of an application to generation of final inspection reports was 232 days for FDA and 204 days for EMA, with no significant differences noted among applications with and without common sites. Conclusion: The inspection processes and timelines between the two agencies were similar, providing support for continued FDA-EMA GCP collaboration. [ABSTRACT FROM AUTHOR]

Knowledge on chronic myelomonocytic leukemia (CMML) patients from Argentina and Brazil is limited. Our series of 280 patients depicted an older age at diagnosis (median 72 years old), 26% of aberrant karyotypes, and a prevalence of myelodysplastic (60%) and CMML-0 subtypes (56%). The median overall survival (OS) was 48.2 months for patients in CMML-0 (Ref.), 24.7 months for those in CMML-1 (HR = 2.0, p = 0.001), and 8.8 months for patients in CMML-2 (HR = 4.6, p < 0.001). In the CMML-0 category, median OS were different between myelodysplastic and myeloproliferative subtypes (63.7 vs 21.2 months, p < 0.001); however, no differences were observed within CMML-1 and CMML-2 subtypes (24.7 vs 23.7 months, p = 0.540, and 9.1 vs 8.2 months, p = 0.160). The prognostic impact of 24 variables and 7 prognostic systems was adjusted to the WHO 2016 after validating their usefulness. Multivariate analysis were performed, and the final model revealed Hb ≥ 8 -< 10g/dL (HR 1.7), Hb < 8g/dL (HR 2.8), poor karyotypes (HR 2.1), WHO 2016-CMML-1 (HR 2.1), and CMML-2 (HR 3.5) as independent adverse clinical parameters in our cohort with a borderline influence of platelets count < 50 × 109/L (HR 1.4). We could validate several scoring systems, the WHO 2016 proposal and its prognostic capability, along with accessible covariates, on predicting the outcome in our series of CMML patients from Latin America. [ABSTRACT FROM AUTHOR]

Background: According to 21 Code of Federal Regulation (CFR) Part 211, Over-the-Counter (OTC) drug manufacturers must establish and follow current good manufacturing practices (cGMP) to produce quality products while meeting regulatory standards. The warning letters issued by the U.S. Food and Drug Administration (FDA) reveal quality inadequacies that may impact the safety and effectiveness of these products. This study provides an analysis of warning letters and cited violations to identify the most common areas of quality issues and to understand the FDA's current thinking on regulatory expectations. Methods: Warning letters between U.S. fiscal years (FY) 2015–2019 were analyzed by the following steps: extraction of CFR violations, categorization of violations, trend analysis of data, and interpretation of results. Results: A total of 116 OTC warning letters and for comparison purposes 561 prescription (Rx) warning letters were analyzed in this study. OTC drug violations relating to product and process controls significantly increased, while violations relating to labeling decreased over the years. Despite these changes in violation numbers, the number of violations increased in most categories, highlighting a continual increase of quality inadequacies. Conclusion: The quality issues are mostly seen in cGMP violations specifically in the drug product, process, and laboratory controls. Most significant violation changes are also seen in drug product and process controls. The overall number of violations in OTC drugs has been increasing in the past 5 years and the analysis results provide a projection for continued increases in violations. Although this study provides an overall quality analysis of OTC warning letters and cited violations, more studies are required to understand the risk to consumers using OTC drug products due to the trends associated with these observations. [ABSTRACT FROM AUTHOR]

Copyright of Zentralblatt fuer Arbeitsmedizin, Arbeitsschutz und Ergonomie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The ability of Staphylococcus aureus to develop multidrug resistance is well documented, and the antibiotic resistance showed by an increasing number of bacteria has shown the need for alternative therapies to treat infections, photodynamic therapy (PDT) being a potential candidate. The aim of this study was to determine the effect of photodynamic therapy as a light-based bactericidal modality to eliminate Staphylococcus aureus. The study investigated a technique based on a combination of light and a photosensitizer that is capable of producing oxidative species to induce a cytotoxic effect. A Staphylococcus aureus suspension was exposed to a light emitting diode (LED) emitting at 628 nm, 14.6 mW/cm(2), and energy density of 20 J/cm(2), 40 J/cm(2), or 60 J/cm(2) in the presence of different porphyrin concentrations (Photogem). Three drug concentrations were employed: 12 microl/ml, 25 microl/ml, and 50 microl/ml. The treatment response was evaluated by the number of bacterial colony forming units (CFU) after light exposure. The results indicated that exposure to 60 J/cm(2) eliminated 100% (10 log(10) scales) of bacteria, on average. The best PDT response rate to eliminate Staphylococcus aureus was achieved with exposure to LED light in combination with the photosensitizer at concentrations ranging from 25 microl/ml to 50 microl/ml. These data suggest that PDT has the potential to eliminate Staphylococcus aureus in suspension and indicates the necessary drug concentration and light fluency. [ABSTRACT FROM AUTHOR]

The article presents a case study on the utility of structured approaches to benefit-risk assessment of pharmaceutical products. The researchers conducted a simulated single-session benefit-risk decision involving three groups using triptan for acute migraine. It implies that the three groups provided consistent value, clarity, and importance of an approval decision.

Aim: To evaluate the push-out bond strength of MTA Fillapex (Angelus) and compare it with ProRoot MTA (Dentsply) and AH Plus (Dentsply). Design: Thirty extracted single-rooted teeth were selected and prepared using a rotary system. The samples were divided randomly into three groups ( n = 10) and obturated, respectively, with: (1) AH Plus + gutta-percha (DiaDent); (2) MTA Fillapex + gutta-percha; (3) ProRoot MTA. Each root was sectioned into 1-mm-thick slices and 30 samples for each group were obtained. The samples were subjected to push-out test. Failure modes were examined under 30× magnification. The results were analysed statistically by one-way ANOVA and Tukey's test. Results: Mean push-out bond strength values were ranked as follows: ProRoot MTA > AH Plus > MTA Fillapex. Statistically significant differences were found among all groups ( p < 0.05). Conclusion: ProRoot MTA had the highest bond strength, whilst MTA Fillapex displayed the lowest values among the groups. [ABSTRACT FROM AUTHOR]

Abstract: Hip fracture has epidemic character in the world, including Serbia, which is significant for its medical and social consequences on the one hand and economic on the other, taking into account the increasing number of elderly in Serbia. Socio-medical aspects of hip or femur fracture were researched on the territory of Belgrade, within two groups of patients, younger (age 20–64) compared to elderly (age 65+). [Copyright &y& Elsevier]

Copyright of Journal of Ultrasound is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To study the efficacy of photodynamic therapy (PDT) with verteporfin in the treatment of juxtafoveal choroidal neovascularization (CNV) secondary to pathologic myopia.Methods: Prospective, open label, two-centre, noncomparative, interventional case series. Consecutive patients with juxtafoveal CNV associated with pathologic myopia were recruited and treated with a standard regimen of PDT with verteporfin. Patients were being followed up every 3-monthly and retreatment was considered when there was evidence of angiographic leakage. Outcome measures included changes in the mean best-corrected visual acuity (BCVA) at the 1-year follow-up when compared with the baseline, the proportion of patients who had stable (within 1 line) and improved visions.Results: A total of 11 eyes from 11 patients with juxtafoveal CNV secondary to pathologic myopia were recruited and all completed the 1-year follow-up. The mean age at presentation was 44.8 years. The refractive error ranged from -6.0 to -15.0 D (+/-SD was -9.55+/-3.04 D). The logMAR BCVA improved from 0.57 to 0.39 at the 1-year follow-up (Wilcoxon signed-ranks test, P=0.027). The mean improvement was 1.8 lines. Five eyes (45.4%) had BCVA improved by >or=3 lines. None of the treated patients had visual loss of >or=1 line. The mean number of treatments over the 12-month study period was 2.3 sessions.Conclusions: The results are encouraging, especially on considering the low retreatment rate, stable or improved BCVA in all treated eyes, and consistently good safety profile. Juxtafoveal myopic CNV may be an expanded indication for PDT with verteporfin. [ABSTRACT FROM AUTHOR]

Background: To compare health status and health services use of Registered First Nations to all other Manitobans (AOM). If the Canadian health care system is meeting underlying need, those experiencing the greatest burden of morbidity and mortality should show the highest rates of health service use.Methods: Registered First Nations' (n = 85,959) hospitalization and physician visit rates were compared to rates of all other Manitobans (n = 1,054,422) for fiscal year 1998/99. The underlying "need" for health care was measured using premature mortality (PMR), an age- and sex-adjusted rate of death before age 75. Data were derived from Manitoba's Population Health Research Data Repository, linked to federal Status Verification System files to determine Registered First Nations status.Results: Registered First Nations' PMR was double the rate of all other Manitobans (6.61 vs. 3.30 deaths per thousand, p < 0.05). Registered First Nations ambulatory physician visit rates (6.13 vs. 4.85 visits per person, p < 0.05), hospital separation rates (0.348 vs. 0.156 separations per person, p < 0.05) and total days of hospital care (1.75 vs. 1.05 days per person, p < 0.05) were higher than AOM rates. Consultation rates (first visit to a specialist) were slightly higher for Registered First Nations (0.29 vs. 0.27 visits per person, p < 0.05), and overall specialist visit rates were lower (0.895 vs. 1.284 visits per person, p < 0.05) compared with AOM.Conclusion: Although hospitalization and ambulatory physician visit rates for First Nations reflect their poorer health status, consult and specialist rates do not reflect the underlying need for health care services. [ABSTRACT FROM AUTHOR]

Background: To examine inequalities in health status of Registered First Nations Manitobans compared to all other Manitobans.Methods: Three mortality indicators--premature mortality rate (PMR) defined as an age- and sex-adjusted rate of death before age 75 years; life expectancy from birth; and potential years of life lost (PYLL)--are compared between Registered First Nations (RFN) people and all other Manitobans (AOM) by geographical areas of Manitoba. Data were derived from the Population Health Research Data Repository, linked to the federal Status Verification System (SVS) files for the years 1995 through 1999.Results: First Nations experienced double the PMR compared to all other Manitobans (6.6 versus 3.3 deaths per thousand, p < 0.05), an eight-year gap in life expectancy (males: 68.4 versus 76.1 years; females 73.2 versus 81.4 years), and over twice the PYLL (males 158.3 versus 62.5 years of life lost per thousand; females 103.3 versus 36.5). RFN male life expectancy was geographically-related (better health status in the north), and inversely related to the corresponding regional AOM life expectancy (r = -0.61, 9 df, one-tailed, p < 0.03). As regional percentage of RFN decreased, male life expectancy decreased (r = 0.77, 9 df, one-tailed, p < 0.003). In contrast, RFN female indicators showed no such relationship.Conclusion: The inequality in health status between RFN and all other Manitobans is large, but also shows differential geographical and gender effects. [ABSTRACT FROM AUTHOR]