Reporting Completeness of Intensity-, Dose-, and Dosage-Related Items in Active Pediatric Upper Limb Neurorehabilitation Trials: A Systematic Review.

OBJECTIVE: To analyze the reporting completeness of the TIDieR items 8-12, in particular intensity, dose, and dosage, in active pediatric upper limb neurorehabilitation trials. DATA SOURCES: We searched PubMed Central, Scopus, CINAHL, OTseeker, and Web of Science for eligible publications. STUDY SELECTION: We included publications analyzing active pediatric upper limb neurorehabilitation interventions and assessed the reporting completeness of 11 items for each intervention and control group. DATA EXTRACTION: Two raters independently screened titles and abstracts and selected the publications using the RYYAN platform. We unblinded the results after the raters had completed their selection and resolved the disagreements by discussion. We used the same procedures to review the full texts. DATA SYNTHESIS: We included 52 randomized controlled trials with 65 intervention and 48 control groups. Authors did not report all 11 items in any of the study groups. The overall reporting completeness varied between 1% (intensity) to 95% (length of the intervention). The reporting completeness of the TIDieR items ranged from 2% (modifications) to 64% (when and how much). We found no significant differences in the reporting completeness between the intervention and control groups. CONCLUSIONS: Information essential for dose-response calculations is often missing in randomized controlled trials of pediatric upper limb neurorehabilitation interventions. Reporting completeness should be improved, and new measures to accurately quantify intensity should be discussed and developed.

[Osteopathy under scrutiny]. / Osteopathie auf dem Prüfstand.

Osteopathic medicine is a medical specialty that enjoys a high level of recognition and increasing popularity among patients. High-quality education and training are essential to ensure good and safe patient treatment. At a superficial glance, osteopathy could be misunderstood as a myth; accurately considered, osteopathic medicine is grounded in medical and scientific knowledge and solid theoretical and practical training. Scientific advances increasingly confirm the empirical experience of osteopathy. Although more studies on its efficacy could be conducted, there is sufficient evidence for a reasonable application of osteopathy. Current scientific studies show how a manually executed osteopathic intervention can induce tissue and even cellular reactions. Because the body actively responds to environmental stimuli, osteopathic treatment is considered an active therapy. Osteopathic treatment is individually applied and patients are seen as an integrated entity. Because of its typical systemic view and scientific interpretation, osteopathic medicine is excellently suited for interdisciplinary cooperation. Further work on external evidence of osteopathy is being conducted, but there is enough knowledge from the other pillars of evidence-based medicine (EBM) to support the application of osteopathic treatment. Implementing careful, manual osteopathic examination and treatment has the potential to cut healthcare costs. To ensure quality, osteopathic societies should be intimately involved and integrated in the regulation of the education, training, and practice of osteopathic medicine.

[Treatment for chronic back pain? : Active multimodal, interdisciplinary pain therapy vs. physiotherapy-physical therapy for chronic back pain]. / Behandlung bei chronischen Rückenschmerzen? : Aktive multimodale, interdisziplinäre Schmerztherapie vs. physiotherapeutisch-physikalische Therapie bei chronischen Rückenschmerzen.

BACKGROUND: In industrialized countries, chronic back pain is referred to as the "number one common disease". OBJECTIVES: Are there any indications of different outcomes of chronic back pain patients when treated with a multimodal, interdisciplinary pain therapy (MMSTh) compared to physiotherapy-physical therapy? MATERIALS AND METHODS: Entrance and final examination by means of survey, questionnaires and physical tests in the intervention and control group, evaluation and comparison of the results. RESULTS: The intervention group showed very significant improvements in all tests. In contrast, the control group achieved only partial improvements in physical parameters and quality of life. This resulted in clear group differences in favor of the MMSTh. In terms of patient satisfaction, the control group showed a better result than the intervention group. CONCLUSIONS: Treatment with MMSTh is superior to standard physiotherapy-physical. Due to the extensive, proven positive effect on many pain-causing and pain-preserving factors, multimodal pain centers should be used more frequently in chronic back pain patients.

Independent contribution of bronchoalveolar lavage and serum galactomannan in the diagnosis of invasive pulmonary aspergillosis.

The optimal combination of galactomannan index (GMI) testing for the diagnosis of invasive pulmonary aspergillosis (IPA) remains unclear. For diagnostic approaches that are triggered by clinical signs and symptoms in high-risk patients, institutional variation remains, with some centers routinely relying on only serum GMI or bronchoalveolar lavage (BAL) GMI testing. In addition, use of mold-active agents before diagnosis of IPA is becoming increasingly common, and understanding the effect of these drugs on test yield is important when making time-critical treatment decisions. In a single-center cohort of 210 allogeneic hematopoietic cell transplant recipients, we found that serum and BAL GMI testing contributed independently to IPA diagnosis, supporting the practice of sending both tests simultaneously to ensure a timely diagnosis of IPA. BAL GMI sensitivity was not affected by receipt of mold-active therapy in our cohort.

GSH-Responsive Drug Delivery System for Active Therapy and Reducing the Side Effects of Bleomycin.

The application of drug delivery system (DDS) has achieved breakthroughs in many aspects, especially in the field of tumor treatment. In this work, polyethylene glycol (PEG)-modified hollow mesoporous manganese dioxide (HMnO2@PEG) nanoparticles were used to load the anti-tumor drug bleomycin (BLM). When the DDS reached the tumor site, HMnO2@PEG was degraded and reduced to Mn2+ by the overexpression of glutathione in the tumor microenvironment, and the drug was released simultaneously. BLM coordinated with Mn2+ in situ, thereby greatly improving the therapeutic activity of BLM. The results of in vivo and in vitro treatment experiments showed that the DDS had excellent responsive therapeutic activation ability. In addition, Mn2+ exhibited strong paramagnetism and was used for T1-weighted magnetic resonance imaging in vivo. Furthermore, this therapeutic mode of responsively releasing drugs and activating in situ effectively attenuated pulmonary fibrosis initiated by BLM. In short, this DDS could help in avoiding the side effects of drugs.

The Impact of Carbapenem Resistance on Mortality in Patients With Klebsiella Pneumoniae Bloodstream Infection: An Individual Patient Data Meta-Analysis of 1952 Patients.

INTRODUCTION: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. METHODS: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). RESULTS: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56-3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24-2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70-4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36-3.59; I2 = 58%). CONCLUSION: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials.

Efficiency of active therapy for low back pain in elderly men.

BACKGROUND: Restoration of functionality in patients with low back pain is one of the most important rehabilitation and societal problems. The aim of this study was to verify the results of the DBC (Documentation Based Care) method used in elderly men. METHOD: This study evaluated the efficiency of DBC treatment on the basis of spinal mobility in sagittal, frontal and transverse planes and a subjective assessment of pain. There were two research groups: one with 187 men over the age of 65, and the other with 187 men under the age of 65. The patients in the study were carefully selected. All subjects suffered from chronic, non-specific low back pain lasting for a period of at least three months. CONCLUSION: The conducted analyses confirmed that a functional restoration process improved spinal mobility in all planes of movement, decreased pain and functional limitations, and reduced the level of depression.

Effectiveness of Active Therapy-Based Training to Improve the Balance in Patients with Fibromyalgia: A Systematic Review with Meta-Analysis.

Balance impairment is a frequent disorder in patients with fibromyalgia (FMS), increasing the risk of falls and decreasing physical function and quality of life. In recent years, the use of active therapy-based training (ATBT) has increased, with the aim of improving balance in women with FMS. Our study aimed to assess the effect of ATBT to improve different balance outcomes in subjects with FMS. A systematic review with meta-analysis was carried out. We searched PubMed Medline, SCOPUS, Web of Science, CINAHL, and PEDro (Physiotherapy Evidence Database) databases up to September 2020. We included randomized controlled trials (RCT) that assessed the balance in patients with FMS after ATBT and compared to other treatments or no intervention. In a random-effects model, the standardized mean difference (SMD) was used to calculate the effect size. Ten studies were included in the review providing data from 546 FMS patients with a mean age of 52.41 ± 2.90 years old (98% females). Our results showed a medium effect favors ATBT with respect to other therapies for monopedal static balance (SMD = 0.571; 95% CI = 0.305, 0.836; p < 0.001), dynamic balance (SMD = 0.618; 95% CI = 0.348, 0.888; p < 0.001), and functional balance (SMD = 0.409; 95% CI = 0.044, 0.774; p = 0.028). No statistically significant differences were found for balance on unstable support. The present meta-analysis showed moderate-quality evidence of a medium effect of ATBT to improve dynamic and functional balance and low-quality evidence of a medium effect to improve monopedal static balance with respect to other therapies or no intervention.

Combined passive and active treatment in strabismic amblyopia with accommodative component.

BACKGROUND: Treatment of amblyopia in esotropic subjects with accommodative component currently consists of optical correction and subsequent occlusion, or penalisation, of the dominant eye. This treatment obtains a good outcome in visual acuity but poor outcomes in binocular vision. An intervention protocol that could improve the outcome of conventional treatment is presented. METHODS: A retrospective study in subjects with amblyopia associated with both fully accommodative and partially accommodative esotropia is presented. Subjects were refracted under cycloplegia and treated with occlusion (passive therapy). Subjects who did not achieve orthotropia through optical correction (partially accommodative esotropia) performed an active therapy (full-time prismatic correction and subsequent fusional vergence therapy or surgery in larger angles > 12 prism dioptres). After treatment, the subjects were examined by a masked optometrist in an external ophthalmology clinic. RESULTS: Twenty-six subjects (12 males and 14 females) aged from six to 13 years (median 8.50; interquartile range [IQR] 3) were included. Median age of detection was three years (IQR 1). All the subjects were hyperopic. In the baseline, median best-corrected visual acuity of the amblyopic eye was 0.40 logMAR (IQR 0.30) and 0.00 logMAR (IQR 0.01) in the dominant eye. After the treatment, the median best-corrected visual acuity in the amblyopic eye was 0.06 logMAR (IQR 0.08). These differences were statistically significant (p < 0.001). All subjects acquired stereoacuity equal or better than 800'' with the Randot Preschool Stereoacuity Test. CONCLUSIONS: The proposed treatment highlights the management of amblyopia in esotropic subjects with accommodative component. This intervention protocol could help to determine if the treatment has to be passive (in fully accommodative esotropia) or a combination of passive and active therapies (in partially accommodative esotropia).

Six-Month Follow-Up of Recovery-Oriented Cognitive Therapy for Low-Functioning Individuals With Schizophrenia.

OBJECTIVE: The study examined six-month follow-up results and the impact of length of illness on treatment outcomes of recovery-oriented cognitive therapy (CT-R). METHODS: Sixty outpatients (mean age 38.4 years, 33% female, 65% African American) with schizophrenia or schizoaffective disorder and elevated negative symptoms were randomly assigned to CT-R or standard treatment. Assessments were conducted at baseline, midtreatment (six and 12 months), end of treatment (18 months), and follow-up (24 months, N=46 after attrition) by assessors blind to treatment condition. Global functioning, measured with the Global Assessment Scale, was the primary outcome. Secondary outcomes were negative symptoms (avolition-apathy score on the Scale for the Assessment of Negative Symptoms) and positive symptoms (total score on the Scale for the Assessment of Positive Symptoms). Length of illness indexed chronicity (less chronic, one to 12 years; more chronic, 13 to 40 years). RESULTS: Intent-to-treat analyses (hierarchal linear modeling) at follow-up indicated significant benefits for individuals assigned to CT-R compared with standard treatment: higher global functioning scores (between-group Cohen's d=.53), lower scores for negative symptoms (d=-.66), and lower scores for positive symptoms (d=-1.36). Length of illness moderated treatment effects on global functioning, such that those with a less chronic illness began to show improvements earlier (at the trend level by six months and reaching significance by the end of treatment), whereas the group with a more chronic illness did not show significant improvements until later (at follow-up). CONCLUSIONS: CT-R produced durable effects that were present even among individuals with the most chronic illness.

The role of regulated clinical trials in the development of bacteriophage therapeutics.

Antibiotic resistance is now recognized as a major, global threat to human health and the need for the development of novel antibacterial therapies has become urgent. Lytic bacteriophages (phages) targeting individual bacterial pathogens have therapeutic potential as an alternative or adjunct to antibiotic use. Bacteriophage therapy has been used for decades, but clinical trials in this field are rare, leaving many questions unanswered as to its effectiveness for many infectious diseases. As a consequence bacteriophage therapy is not used or accepted in most parts of the world. The increasing need for new antimicrobial therapies is driving the development of bacteriophage therapies for a number of diseases but these require the successful completion of large-scale clinical trials in accordance with US FDA or European EMA guidelines. Bacteriophages are considered as biological agents by regulatory authorities and they are managed by biological medicinal products guidelines for European trials and guidelines of the division of vaccines and related product applications in the USA. Bacteriophage therapy is typically an 'active' treatment requiring multiplication in the bacterial host and therefore the factors that govern its success are different from those of conventional antibiotics. From the pharmacokinetic and pharmacodynamic points of view, time of treatment, dosage depending on the site of infection and the composition of the bacteriophage formulation (single vs multiple strains) need careful consideration when designing clinical trials. Scientific evidence regarding inflammatory effects, potential for gene transfer and phage resistance, need to be evaluated through such trials. However purity, stability and sterility of preparations for human use can be addressed through Good Manufacturing Practises to reduce many potential safety concerns. In this review we discuss the potential for the development of bacteriophage therapy in the context of critical aspects of modern, regulated clinical trials.