Surface Modification of lactose carrier particles using a fluid bed coater to improve fine particle fraction for dry powder inhalers.

Surface roughness of carrier particles can impact dry powder inhaler (DPI) performance. There are opposing views on the effect of roughness on DPI performance. Hence, a systematic approach is needed to modify carrier surfaces and evaluate the impact on drug delivery. Carrier particle surfaces were modified by fluid bed coating with saturated lactose containing micronized lactose of different sizes (2, 5 and 8 µm) and coated to different levels (20, 40, 60 and 80%). Their drug delivery performance was assessed by the fine particle fraction (FPF). Roughness parameters, mean arithmetic roughness (Ra) and arithmetic mean height (Sa), of the carrier particles, were also evaluated using optical profilometry and scanning laser microscopy. Generally, particles of higher Ra had higher FPF. Higher Sa resulted in higher FPF only for particles with 60 and 80% coat levels. Reduced contact surface area between the drug particle and rougher carrier particle resulted in easier drug detachment during aerosolization. The 5 µm micronized lactose produced optimal carrier particles with respect to FPF and surface roughness. The study highlighted that with the ideal particles for surface roughening and coating level, surface roughening could be efficiently achieved by fluid bed coating for superior DPI performance.

Global, regional, and national burden of uterine fibroids in the last 30 years: Estimates from the 1990 to 2019 Global Burden of Disease Study.

Objective: To study specific information on trends in incidence, mortality, disability-adjusted life years (DALY) and the corresponding trends among five sociodemographic index regions, 21 regions, and 204 countries for decision-making, which would enable policymakers to distribute limited resources and devise policies more rationally. Methods: Data on uterine fibroids (UNs) from 1990 to 2019, including incidence, mortality, and DALYs, were obtained from the 2019 Global Burden of Disease Study. An estimated annual percentage change (EAPC) was calculated to assess morbidity, mortality, and DALY trends. Results: The incident cases of UFs increased from 5,769,658 (95%UI, 7,634,3995-4,274,824) incidences in 1990 to 9,643,336 (95%UI, 7,178,053-12,714,741) incidences in 2017, and the age-standardized incidence rate was steady at 225.67/100,000 persons (95%UI, 167.33-298.87) in 1990 to 241.18/100,000 persons (95%UI, 179,45-318.02) in 2019. The incidence ratio in the high sociodemographic index (SDI) region showed a unimodal distribution, with peaks in 2005. Between 2009 and 2017, the age-standardized death rate of UFs declined globally, especially in low-SDI and low-middle SDI regions. In contrast with 860,619 DALYs (95%UI, 473,067-1,505,289) in 1990, the number of DALYs was 1,378,497 (95%UI, 710,915-2,475,244) in 2019, which had increased significantly, whereas the age-standardized DALY rate decreased expressively with an EAPC of -1.93 (95%CI, from -2.16 to -1.71). Conclusion: The global burden of UFs increased between 1990 and 2019, and the incidences and DALYs increased prominently worldwide, while the deaths from UFs had no evident growth. Lower SDI regions carried an incremental burden of UFs, while disease reduction was observed in higher SDI regions. It is high time we paid attention to the underprivileged regional quality of life and health protection.

Association between maternal breastfeeding and risk of systemic neoplasms of offspring.

BACKGROUND: Breastfeeding might prevent childhood cancer by stimulating the immune system. METHODS: The following databases, including PubMed, Embase, and Cochrane Library, were searched from inception to January 10, 2021. RESULTS: In dose-dependent manner, there was a statistically significant inverse association between any breastfeeding and the incidence of childhood cancer. There was no evidence that breastfeeding was inversely related to childhood cancer of the skeletal, reproductive, or sensory systems. However, breastfeeding was inversely associated with the incidence of hematological malignancies and cancers of the nervous and urinary systems. Among hematological malignancies, the relationship was significant for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), but not for acute non-lymphocytic leukemia (ANLL), Hodgkin's lymphoma (HL), or non-HL. CONCLUSIONS: The evidences demonstrated that breastfeeding have a potential protective role in preventing selective childhood cancer growth, especially for ALL, AML, cancer of nervous and urinary systems. This study recommended that breastfeeding be extended for as long as possible or maintained for at least 6 months to prevent selective childhood cancer growth.

Cognitive behavioral therapy for children and adolescents with post-traumatic stress disorder: meta-analysis.

BACKGROUND: Children and adolescents who experience traumatic events may develop post-traumatic stress disorder (PTSD), which is often associated with other psychiatric disorders, including depression and anxiety. Cognitive behavioral therapy (CBT) is widely used in psychotherapy to treat PTSD in children and adolescents. This meta-analysis evaluated previous studies on the effectiveness of CBT in the treatment of PTSD in children and adolescents. METHODS: Randomized controlled trials (RCTs) published before July 25, 2021, were retrieved from seven databases. All RCTs of CBT compared to control, including conventional treatment or other treatments, in children or adolescents with PTSD. Random effect models were employed for all outcomes. Risk of bias was performed by Cochrane Collaboration's tool. The publication bias was evaluated using the Egger's regression analysis. RESULTS: Nineteen RCTs were included in the meta-analysis. Compared with control, CBT was effective in reducing the symptoms of PTSD in children and adolescents, with a variety of scales used to measure the overall PTSD symptoms: CAPS (SMD = -0.41, 95%CI [-0.71, -0.12]), CPSS (SMD = -0.88, 95%CI [-1.42, -0.34]) and UCLA-PTSD RI (SMD = -1.70, 95%CI [-2.98, -0.42]). Furthermore, CBT also improved the comorbidities of depression (SMD = -0.43, 95%CI [-0.70, -0.17]) and anxiety (SMD = -0.29, 95%CI [-0.56, -0.03]) associated with PTSD. However, CBT was not effective in reducing avoidance symptoms (SMD = 0.38, 95%CI [-0.55, 1.31]). CONCLUSION: CBT can reduce the severity of PTSD in children and adolescents and improve the symptoms of depression and anxiety, as evident in the treatment of PTSD victims of sexual abuse and war and in patients aged more than 7 years.

Effectiveness, Acceptability and Safety of Pharmaceutical Management for Combat-Related PTSD in Adults Based on Systematic Review of Twenty-Two Randomized Controlled Trials.

Objective: This study assessed the efficacy, acceptability, and safety of pharmaceutical management for combat-related post-traumatic stress disorder (PTSD) to provide a clinical decision-making basis for clinicians. Method: A comprehensive search was conducted using Ovid MEDLINE, Ovid EMBASE, Cochrane Library, Scopus, ScienceDirect, and Web of Science for randomized controlled trails (RCTs), which reported pharmaceutical management and placobo for adults with combat-related PTSD, that were published until April 21, 2021. The effectiveness, acceptability, and adverse events (AEs), were designed as interested outcomes. The change in total symptoms of combat-related PTSD according to the clinician rating scale was defined as primary outcome, and the others were defined as secondary outcomes. Results: Twenty-two RCTs with 1,221 patients were involved. Compared with placebo, overall active comparators had statistical differences for all outcomes, including the change in total symptoms of combat-related PTSD [SMD = -0.36, 95%CI (-0.62,-0.09)], depression [SMD = -0.28, 95%CI (-0.45,-0.10)], anxiety [SMD = -0.44, 95%CI (-0.64,-0.23)], re-experience [SMD = -0.33, 95%CI (-0.52,-0.13)], avoidance [SMD = -0.24, 95%CI (-0.43,-0.05)], and hyper-arousal [SMD = -0.26, 95%CI (-0.48,-0.03)]. Compared with the placebo, in terms of acceptability, overall active comparators did not significantly decrease all-cause discontinuance rates [RR = 0.97, 95%CI (0.78,1.20)], and the significance decreased due to AEs [RR = 2.42, 95%CI (1.41,4.13)]. Nevertheless, overall there was no statistically significant difference for overall AEs, including somnolence, sedation, dizziness, paresthesia, anxiety, blurred vision, generalized anxiety disorder, and sleep disturbance. All funnel plots were symmetrical and no publication bias was found. Conclusion: Active drugs, especially amitriptyline, imipramine, and quetiapine, had a positive effect on the improvement of combat-related PTSD symptoms. Despite there being no significant increase in the AEs of the active drugs, the fact that the discontinuation rates of these drugs, including risperidone, imipramine, and topiramate, were increased deserves attention. Furthermore, as active drugs were effective across ethnic groups and battlefields, active drug regimens were revealed to be more appropriate for treating people with symptoms of extreme severe PTSD (≥80) or PTSD that is at least 8 weeks old. In addition, current evidence was from adults under 60 years of age and male combat-related PTSD. Whether this evidence can be extended to other populations of combat-related PTSD needs to be confirmed by subsequent high-quality, large-sample studies.

Meta-Analysis of Randomized Controlled Trials Using Botulinum Toxin A at Different Dosages for Urinary Incontinence in Patients With Overactive Bladder.

Background: Urinary incontinence (UI) is a common and refractory complication for patients with neurogenic detrusor overactivity (NDO) or idiopathic overactive bladder (IOAB). Objectives: To evaluate the effect of Botulinum toxin A (BTX-A) based on different dosages strategy for UI. Method: The MEDLINE, Ovid EMbase, The Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Internet (CNKI), and WanFang database were searched for relevant published randomized controlled trials (RCTs) between 1969 to September 31, 2018. All database were searched to identify relevant randomized controlled trials (RCTs) that investigated the clinical benefit of BTX-A for management of UI in patients with NDO and IOAB. Results: This meta-analysis involved 19 original studies. The BTX-A was superior to placebo in reducing episodes of UI for NDO patients in all subgroups of different dosages for different durations, and also reduced maximum detrusor pressure in all kinds of 200U and 300U at 6 weeks. However, it increased post void residual in different dosages of 200U at 2 weeks. For IOAB patients, compared to placebo, BTX-A increased detrusor compliance for different dosages of 200U and 300U at 12 and 36 weeks, but it increased risk of urinary tract infections at other dosages. Conclusions: This meta-analysis indicated that BTX-A 200U and 300U are more effective than placebo in the treatment of NDO, with minimal, local, and manageable adverse events. Furthermore, BTX-A 300U and 200U could also improve detrusor compliance of IOAB. However, more RCTs would still be necessary to explore the effect of BTX-A on management of UI in NDO and IOAB patients.