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Ramona Meister Mariam Abbas Jochen Antel Triinu Peters Yiqi Pan Ulrike Bingel Yvonne Nestoriuc Johannes Hebebrand 《European child & adolescent psychiatry》2020,29(3):253-273
Children and adolescents with major depressive disorder (MDD) appear to be more responsive to placebo than adults in randomized placebo-controlled trials (RCTs) of second and newer generation antidepressants (SNG-AD). Previous meta-analyses obtained conflicting results regarding modifiers. We aimed to conduct a meta-analytical evaluation of placebo response rates based on both clinician-rating and self-rating scales. Based on the most recent and comprehensive study on adult data, we tested whether the placebo response rates in children and adolescents with MDD also increase with study duration and number of study sites. We searched systematically for published RCTs of SNG-AD in children and/or adolescents (last update: September 2017) in public domain electronic databases and additionally for documented studies in clinical trial databases. The log-transformed odds of placebo response were meta-analytically analyzed. The primary and secondary outcomes were placebo response rates at the end of treatment based on clinician-rating and self-rating scales, respectively. To examine the impact of study duration and number of study sites on placebo response rates, we performed simple meta-regression analyses. We selected other potential modifiers of placebo response based on significance in at least one previous pediatric meta-analysis and on theoretical considerations to perform explorative analyses. We applied sensitivity analyses with placebo response rates closest to week 8 to compare our data with those reported for adults. We identified 24 placebo-controlled trials (2229 patients in the placebo arms). The clinician-rated placebo response rates ranged from 22 to 62% with a pooled response rate of 45% (95% CI 41–50%). The number of study sites was a significant modifier in the simple meta-regression analysis [odds ratio (OR) 1.01, 95% CI 1.01–1.02, p = 0.0003, k = 24) with more study sites linked to a higher placebo response. Study duration was not significantly associated with the placebo response rate. The explorative simple analyses revealed that publication year may be an additional modifier. However, in the explorative multivariable analysis including the number of study sites and the publication year only the number of study sites reached a p value ≤ 0.05. The self-rated placebo response rates ranged from 1 to 68% with a pooled response rate of 26% (95% CI 10–54%) (k = 6; n = 396). This meta-analysis confirms a high pooled placebo response rate in children and adolescents based on clinician ratings, which exceeds that observed in the most recent meta-analysis of placebo effects in adults (36%; 95% CI 35–37%) published in 2016. However, and similar to findings in adults, the pooled response rates based on self-ratings were substantially lower. In accordance with previous meta-analyses, we corroborated the number of study sites as significant modifier. In comparison to the recent adult meta-analysis, the substantially lower number of pediatric studies entails a reduced power to detect modifiers. Future studies should provide more precise and homogenous information to support discovery of potential modifiers and consider no-treatment—if ethically permissible—to allow differentiation between placebo and spontaneous remission rates. If these differ, practicing clinicians should facilitate placebo effects as an addition to the verum effect to maximize benefits. Further research is required to explain the discrepant response rates between clinician and self-ratings. 相似文献
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Antonella Rosario Ramona Cceres Adriana Soledad Vega Orozco Ricardo Jorge Cabrera Myriam Raquel Laconi 《Journal of neuroendocrinology》2020,32(3)
The present study aimed to determine whether an i.c.v. administration of allopregnanolone (ALLO) rapidly modifies the hypothalamic and ovarian 3β‐hydroxysteroid dehydrogenase (3β‐HSD) enzymatic activity and gene expression in in vivo and ex vivo systems in pro‐oestrus (PE) and dioestrus I (DI) rats. Animals were injected with vehicle, ALLO, bicuculline or bicuculline plus ALLO and were then killed. In the in vivo experiment, the hypothalamus, ovaries and serum were extracted and analysed. In the ex vivo experiment, the superior mesenteric ganglion ‐ ovarian nerve plexus ‐ ovary system was extracted and incubated during 120 minutes at 37 ºC. The serum and ovarian compartment fluids were used to determine progesterone by radioimmunoanalysis. In the in vivo experiments, ALLO caused a decrease in hypothalamic and ovarian 3β‐HSD enzymatic activity during PE. During DI, ALLO increased hypothalamic and ovarian 3β‐HSD activity and gene expression. The ovarian 3β‐HSD activity increased in both stages in the ex vivo system; gene expression increased only during DI. ALLO induced an increase in serum progesterone only in D1 and in the ovarian incubation liquids in both stages. All findings were reversed by an injection of bicuculline before ALLO. Ovarian steroidogenic changes could be attributed to signals coming from ganglion neurones, which are affected by the acute central neurosteroid stimulation. The i.c.v. administration of ALLO via the GABAergic system altered 3β‐HSD activity and gene expression, modulating the neuroendocrine axis. The present study reveals the action that ALLO exerts on the GABAA receptor in both the central and peripheral nervous system and its relationship with hormonal variations. ALLO is involved in the “fine tuning” of neurosecretory functions as a potent modulator of reproductive processes in female rats. 相似文献
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Ramona Schuppner Justus Maehlmann Meike Dirks Hans Worthmann Anita B. Tryc Kajetan Sandorski Elisabeth Bahlmann Jan T. Kielstein Anja M. Giesemann Heinrich Lanfermann Karin Weissenborn 《Medicine》2016,95(6)
In an outbreak of shiga toxin-producing Escherichia coli infections and associated hemolytic-uremic syndrome (STEC O104:H4) in Germany in the year 2011 neurological complications in adult patients occurred unexpectedly frequent, ranging between 48% and 100% in different patient groups. Few is known about the long-term effects of such complications and so we performed follow-up exams on 44 of the patients treated for STEC-HUS at Hannover Medical Scool in this observational study. Standardized follow-up exams including neurological and neuropsychological assessments, laboratory testing, magnetic resonance imaging (MRI), and EEG were carried out. Subgroups were examined 2 (n = 34), 7 (n = 22), and 19 (n = 23) months after disease onset. Additionally, at the 19-month follow-up, quality of life, sleep quality, and possible fatigue were assessed.Nineteen months after disease onset 31 patients were reassessed, 22 of whom still suffered from symptoms such as fatigue, headache, and attention deficits. In the neuropsychological assessments only 39% of the patients performed normal, whereas 61% scored borderline pathological or lower. Upon reviewal, the follow-up data most prominently showed a secondary decline of cognitive function in about one-quarter of the patients. Outcome was not related to treatment or laboratory data in the acute phase of the disease nor length of hospitalization. Prognosis of STEC-HUS associated brain dysfunction in adults with regard to severity of symptoms is mostly good; some patients however still have not made a full recovery. Patients’ caretakers have to be aware of possible secondary decline of brain function as was observed in this study. 相似文献
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Yelda Jozaghi Mark E. Zafereo Nancy D. Perrier Jennifer R. Wang Elizabeth Grubbs Neil D. Gross Sarah Fisher Erich M. Sturgis Ryan P. Goepfert Stephen Y. Lai Conor Best Naifa L. Busaidy Maria E. Cabanillas Ramona Dadu Robert F. Gagel Mouhammed A. Habra Mimi I. Hu Camilo Jimenez Steven I. Sherman Sonali Thosani Jeena Varghese Steven G. Waguespack Steven Weitzman Anita K. Ying Paul H. Graham 《Head & neck》2020,42(6):1325-1328
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Lise Kirstine Kvisgaard Charlotte Sonne Kristensen Pia Ryt‐Hansen Kasper Pedersen Tomasz Stadejek Ramona Trebbien Lars Ole Andresen Lars Erik Larsen 《Transboundary and Emerging Diseases》2020,67(5):1786-1796
Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent in Danish swine herds. In July 2019, PRRSV‐1 was detected in a PRRSV‐negative boar station and subsequently spread to more than 38 herds that had received semen from the boar station. Full genome sequencing revealed a sequence of 15.098 nucleotides. Phylogenetic analyses showed that the strain was a recombination between the Amervac strain (Unistrain PRRS vaccine; Hipra) and the 96V198 strain (Suvaxyn PRRS; Zoetis AH). The major parent was the 96V198 strain that spanned ORFs 1–2 and part of ORF 3 and the minor parent was the Amervac strain, which constituted the remaining part of the genome. The virus seems to be highly transmissible and has caused severe disease in infected herds despite a high level of genetic identity to the attenuated parent strains. The source of infection was presumable a neighbouring farm situated 5.8 km from the boar station. 相似文献
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A. Parker Ruhl Minxuan Huang Elizabeth Colantuoni Taruja Karmarkar Victor D. Dinglas Ramona O. Hopkins Dale M. Needham With the National Institutes of Health National Heart Lung Blood Institute Acute Respiratory Distress Syndrome Network 《Intensive care medicine》2017,43(7):980-991
Purpose
To evaluate (1) post-discharge healthcare utilization and estimated costs in ARDS survivors, and (2) the association between patient and intensive care-related variables, and 6-month patient status, with subsequent hospitalization and costs.Methods
Longitudinal cohort study enrolling from four ARDSNet trials in 44 US hospitals. Healthcare utilization was collected via structured interviews at 6 and 12 months post-ARDS, and hospital costs estimated via the Medical Expenditure Panel Survey. Adjusted odds ratios for hospitalization and adjusted relative medians for hospital costs were calculated using marginal two-part regression models.Results
Of 859 consenting survivors, 839 (98%) reported healthcare utilization, with 52% female and a mean age of 49 years old. Over 12 months, 339 (40%) patients reported at least one post-discharge hospitalization, with median estimated hospital costs of US$18,756 (interquartile range $7852–46,174; 90th percentile $101,500). Of 16 patient baseline and ICU variables evaluated, only cardiovascular comorbidity and length of stay were associated with hospitalization, and sepsis was associated with hospital costs. At 6-month assessment, better patient-reported physical activity and quality of life status were associated with fewer hospitalizations and lower hospital costs during subsequent follow-up, and worse psychiatric symptoms were associated with increased hospitalizations.Conclusions
This multicenter longitudinal study found that 40% of ARDS survivors reported at least one post-discharge hospitalization during 12-month follow-up. Few patient- or ICU-related variables were associated with hospitalization; however, physical, psychiatric, and quality of life measures at 6-month follow-up were associated with subsequent hospitalization. Interventions to reduce post-ARDS morbidity may be important to improve patient outcomes and reduce healthcare utilization.10.
Joel M. Baumgartner Alyssa Krasinskas Mustapha Daouadi Amer Zureikat Wallis Marsh Kenneth Lee David Bartlett A. James Moser Herbert J. Zeh III 《Journal of gastrointestinal surgery》2012,16(6):1152-1159