Quality of life of pediatric and adult individuals with osteogenesis imperfecta: a meta-analysis

Background Osteogenesis imperfecta (OI) is a group of rare inheritable disorders of connective tissue. The cardinal manifestations of OI are low bone mass and reduced bone mineral strength, leading to increased bone fragility and deformity that may lead to significant impairment in daily life. The phenotypic manifestations show a broad range of severity, ranging from mild or moderate to severe and lethal. The here presented meta-analysis aimed to analyze existing findings on quality of life (QoL) in children and adults with OI. Methods Nine databases were searched with predefined key words. The selection process was executed by two independent reviewers and was based on predetermined exclusion and inclusion criteria. The quality of each study was assessed using a risk of bias tool. Effect sizes were calculated as standardized mean differences. Between-study heterogeneity was calculated with the I$^{2}$ statistic. Results Among the studies included two featured children and adolescents (N = 189), and four adults (N = 760). Children with OI had significantly lower QoL on the Pediatric quality of life inventory (PedsQL) with regards to the total score, emotional, school, and social functioning compared to controls and norms. The data was not sufficient to calculate differences regarding OI-subtypes. In the adult sample assessed with Short Form Health Survey Questionnaire, 12 (SF-12) and 36 items (SF-36), all OI types showed significantly lower QoL levels across all physical component subscales compared to norms. The same pattern was found for the mental component subscales namely vitality, social functioning, and emotional role functioning. The mental health subscale was significantly lower for OI type I, but not for type III and IV. All of the included studies exhibited a low risk of bias. Conclusions QoL was significantly lower in children and adults with OI compared to norms and controls. Studies in adults comparing OI subtypes showed that the clinical severity of the phenotype is not related to worse mental health QoL. Future research is needed to examine QoL in children and adolescents in more sophisticated ways and to better understand the association between clinical severity of an OI-phenotype/severity and mental health in adults

Task failure from inspiratory resistive loaded breathing: a role for inspiratory muscle fatigue?

The use of non-invasive resistive breathing to task failure to assess inspiratory muscle performance remains a matter of debate. CO2 retention rather than diaphragmatic fatigue was suggested to limit endurance during inspiratory resistive breathing. Cervical magnetic stimulation (CMS) allows discrimination between diaphragmatic and rib cage muscle fatigue. We tested a new protocol with respect to the extent and the partitioning of inspiratory muscle fatigue at task failure. Nine healthy subjects performed two runs of inspiratory resistive breathing at 67 (12)% of their maximal inspiratory mouth pressure, respiratory rate ( f R), paced at 18min-1, with a 15-min pause between runs. Diaphragm and rib cage muscle contractility were assessed from CMS-induced esophageal (P es,tw), gastric (P ga,tw), and transdiaphragmatic (P di,tw) twitch pressures. Average endurance times of the first and second runs were similar [9.1 (6.7)and 8.4 (3.5)min]. P di,tw significantly decreased from 33.1 to 25.9cmH2O in the first run, partially recovered (27.6cmH2O), and decreased further in the second run (23.4cmH2O). P es,tw also decreased significantly (-5.1 and -2.4cmH2O), while P ga,tw did not change significantly (-2.0 and -1.9cmH2O), indicating more pronounced rib cage rather than diaphragmatic fatigue. End-tidal partial pressure of CO2 (P ETCO2) rose from 37.2 to 44.0 and 45.3mmHg, and arterial oxygen saturation (S aO2) decreased in both runs from 98% to 94%. Thus, task failure in mouth-pressure-targeted, inspiratory resistive breathing is associated with both diaphragmatic and rib cage muscle fatigue. Similar endurance times despite different degrees of muscle fatigue at the start of the runs indicate that other factors, e.g. increases in P ETCO2, and/or decreases in S aO2, probably contributed to task-failur

Staphylococcus aureus Small Colony Variants in Prosthetic Joint Infection

Background. Small colony variants of Staphylococcus aureus tend to persist despite antimicrobial therapy, especially when involved in implant-associated infections. Methods. We analyzed 5 cases of hip prosthesis-associated infections due to small colony variants, including their course prior to identification of the pathogen. Biopsy investigations included microbiological examination and, in 1 case, transmission electron microscopy to detect intracellular bacteria in nonprofessional phagocytes. A treatment concept was elaborated on the basis of a published algorithm and patients were managed accordingly. Results. The patients' mean age was 62.2 years. All patients experienced treatment failures prior to isolation of small colony variants, despite as many as 3 surgical revisions and up to 22 months of antibiotics. Transmission electron microscopy performed on biopsy specimens from periprosthetic tissue revealed intracellular cocci in fibroblasts. All prostheses were removed without implanting a spacer, and antimicrobial agents were administered for 5.5-7 weeks. Reimplantation of the prosthesis was performed for 4 patients. Follow-ups were uneventful in all 5 cases. Conclusions. In the case of a poor response to adequate antimicrobial and surgical treatment in implant-associated staphylococcal infections, small colony variants should be considered and actively sought. In our case series, a 2-stage exchange without implantation of a spacer combined with antimicrobial therapy for an implant-free interval of 6-8 weeks was associated with successful outcome, with a mean follow-up of 24 month

Reflectance spectra of synthetic Fe-free ortho- and clinoenstatites in the UV/ VIS/IR and implications for remote sensing detection of Fe-free pyroxenes on planetary surfaces

For a better spectral characterization of planetary bodies with enstatite-rich surfaces like Mercury or E-type asteroids, we synthesized two different enstatite (Mg2Si2O6) polymorphs: Orthoenstatite and clinoenstatite. Both enstatite polymorphs are known from the meteorite record and are commonly observed in aubrites and enstatite chondrites. The synthesized enstatites are particulate samples suitable for laboratory reflectance measurements and can be used for compositional modelling by preparing mixtures of samples in the laboratory or by using the sample's spectra in mathematical models. We report on the synthesis process, chemical composition, grain size distribution, and reflectance spectra of these synthetic enstatites covering the wavelength range from 0.25 to 17 μm, compare them to other pyroxenes (meteoritic enstatite and other synthetic enstatites and diopside), and discuss the implications of retrieving surface compositions of planetary bodies like E-type asteroids, comets, or Mercury. Both enstatite spectra are very bright in the VIS and NIR and show almost neutral to slightly bluish spectral slopes with a steep absorption in the UV. Very low iron in the enstatites (below ~0.04 wt% FeO) already results in weak albeit noticeable absorptions in the VNIR between 0.4 and 0.9 μm. Orthoenstatite and clinoenstatite are not distinguishable based only on their spectra in the VIS and NIR. At the Reststrahlen bands in the MIR a systematic difference in the number and exact position of local minima at ~10 μm between clinoenstatite and orthoenstatite is evident. This can be used to discern between the polymorphs in this wavelength range. Additionally, we can distinguish between Fe-free low- and high-Ca pyroxenes in the MIR

Kinomic exploration of temozolomide and radiation resistance in Glioblastoma multiforme xenolines

Glioblastoma multiforme (GBM) represents the most common and deadly primary brain malignancy, particularly due to temozolomide (TMZ) and radiation (RT) resistance. To better understand resistance mechanisms, we examined global kinase activity (kinomic profiling) in both treatment sensitive and resistant human GBM patient-derived xenografts (PDX or “xenolines”)

Caregiver burden, and parents' perception of disease severity determine health-related quality of life in paediatric patients with intoxication-type inborn errors of metabolism.

Background Living with a non-acute (phenylketonuria) or acute (e.g. urea cycle disorders, organic acidurias) intoxication-type inborn error of metabolism (IT-IEM) can have a substantial impact on health-related quality of life (HrQoL) of paediatric patients and their families. Parents take primary responsibility for treatment monitoring and experience worry and fear about their child's health status. Quantitative evidence on parental psychological factors which may influence the HrQoL of patients with IT-IEM are sparse to non-existent. Methods In this multicenter survey study 50 parents of IT-IEM patients (ages 5-19) assessed the severity of their child's disease, reported on caregiver burden, and proxy-rated their child's HrQoL. Additionally, 35 patient self-reports on HrQoL were obtained (n = 16 female patients, n = 19 male patients). Multiple linear regressions were conducted to examine the predictive power of child age, sex, medical diagnosis type (acute / non-acute), parental perceived disease severity and caregiver burden on patients' HrQoL. Mediation analyses were used to investigate the relation of caregiver burden and parental ratings of disease severity with patients' HrQoL. Results Significant regression models for self-reported [F(5,34) = 10.752, p < .001, R 2 adj.. = 0.59] and parent proxy reported HrQoL [F(5,49) = 20.513, p < .001, R 2 adj.. = 0.67] emerged. High caregiver burden and perceived disease severity predicted significantly lower patient self- and proxy-reported HrQoL while type of diagnosis (acute versus non-acute) did not. Female sex predicted significantly lower self-reported HrQoL. High caregiver burden was the mediating factor between high perceived severity of the child's disease and lower proxy- by parent rated HrQoL. Conclusion Detecting elevated burden of care and providing support for parents seems crucial to prevent adverse consequences for their children's HrQoL. Intervention studies are needed, to assess which support programs are most efficient

A randomized controlled trial of an Internet-based intervention for eating disorders and the added value of expert-patient support: study protocol

Background: E-mental health has become increasingly popular in interventions for individuals with eating disorders (EDs). It has the potential to offer low-threshold interventions and guide individuals to the needed care more promptly. Featback is such an Internet-based intervention and consists of psychoeducation and a fully automated monitoring and feedback system. Preliminary findings suggest Featback to be (cost-)effective in reducing ED symptomatology. Additionally, e-mail or chat support by a psychologist did not enhance the effectiveness of Featback. Support by an expert patient (someone with a lived experience of an ED) might be more effective, since that person can effectively model healthy behavior and enhance self-efficacy in individuals struggling with an ED. The present study aims to replicate and build on earlier findings by further investigating the (cost-)effectiveness of Featback and the added value of expert-patient support. Methods: The study will be a randomized controlled trial with a two-by-two factorial design with repeated measures. The four conditions will be (1) Featback, in which participants receive automated feedback on a short monitoring questionnaire weekly, (2) Featback with weekly e-mail or chat support from an expert patient, (3) weekly support from an expert patient, and (4) a waiting list. Participants who are 16 years or older and have at least mild self-reported ED symptoms receive a baseline measure. Subsequently, they are randomized to one of the four conditions for 8 weeks. Participants will be assessed again post-intervention and at 3, 6, 9, and 12 months follow-up. The primary outcome measure will be ED psychopathology. Secondary outcome measures are experienced social support, self-efficacy, symptoms of anxiety and depression, user satisfaction, intervention usage, and help-seeking attitudes and behaviors. Discussion: The current study is the first to investigate e-mental health in combination with expert-patient support for EDs and will add to the optimization of the delivery of Internet-based interventions and expert-patient support. Trial registration: Netherlands Trial Register, NTR7065. Registered on 7 June 2018

Patient and surgery related factors associated with fatigue type polyethylene wear on 49 PCA and DURACON retrievals at autopsy and revision

<p>Abstract</p> <p>Background</p> <p>Polyethylene wear is an important factor for longevity of total knee arthroplasty. Proven and suspicious factors causing wear can be grouped as material, patient and surgery related. There are more studies correlating design and/or biomaterial factors to in vivo wear than those to patient and surgery related factors. Many retrieval studies just include revision implants and therefore may not be representative. This study is aimed to correlate patient- and surgery- related factors to visual wear score by minimizing design influence and include both autopsy and revision implants. Comparison between the groups was expected to unmask patient and surgery-related factors responsible for wear.</p> <p>Methods</p> <p>The amount of joint side wear on polyethylene retrievals was measured using a modification of an established visual wear score. Fatigue type wear was defined as summation of the most severe wear modes of delamination, pitting and cracks. Analysis of patient and surgery related variables suspicious to cause wear included prospectively sampled patient activity which was measured by self reported walking capacity. Statistical analysis was done by univariate analysis of variance. Activity level and implantation time were merged to an index of use and correlated to the wear score.</p> <p>Results</p> <p>Wear score after comparable implantation time was significantly less in the autopsy group. Even so, fatigue type wear accounted for 84 and 93 % of total wear score on autopsy and revision implants respectively. A highly significant influence on wear score was found in time of implantation (p = 0.002), level of activity (p = 0.025) and inserts belonging to revision group (p = 0.006). No influence was found for the kind of patella replacement (p = 0.483). Body mass index and accuracy of component alignment had no significant influence on visual wear score. Fatigue-type wear in the medial compartment was closely correlated to the index of use in the autopsy (R²= 0.383) and the revision group (R²= 0.813).</p> <p>Conclusion</p> <p>The present study's finding of substantial fatigue type wear in both autopsy and revision retrievals supports the theory that polyethylene fatigue strength is generally exceeded in this type of prosthesis. Furthermore, this study correlated fatigue-type polyethylene wear to an index of use as calculated by activity over time. Future retrieval studies may use activity over time as an important patient related factor correlated to the visual wear score. When evaluating total knee arthroplasty routine follow up, the surgeon must think of substantial wear present even without major clinical signs.</p