Biodegradable fixation systems could reduce/delete the problems associated with titanium plate removal. This means less surgical discomfort, and a reduction in costs.
The aim of the present study was ...to compare the cost-effectiveness between a biodegradable and a titanium system in Maxillofacial surgery.
This multicenter RCT was performed in the Netherlands from December 2006 to July 2009. Included were 230 patients who underwent a bilateral sagittal split osteotomy (BSSO), a Le Fort-I osteotomy, or a bi-maxillary osteotomy and those treated for fractures of the mandible, maxilla, or zygoma. The patients were randomly assigned to a titanium group (KLS Martin) or to a biodegradable group (Inion CPS). Costs were assessed from a societal perspective. Health outcomes in the incremental cost-effectiveness ratio (ICER) were bone healing (8 weeks) and plate removal (2 years).
In 25 out of the 117 patients who were randomized to the biodegradable group, the maxillofacial surgeon made the decision to switch to the titanium system intra-operatively. This resulted in an Intention-To-Treat (ITT-)analysis and a Treatment-Received (TR-) analysis. Both analyses indicated that operations performed with titanium plates and screws had better health outcomes. In the TR-analysis the costs were lower in the biodegradable group, in the ITT-analysis costs were lower in the titanium group.
The difference in costs between the ITT and the TR analyses can be explained by the intra-operative switches: In the TR-analysis the switches were analysed in the titanium group. In the ITT-analysis they were analysed in the biodegradable group. Considering the cost-effectiveness the titanium system is preferable to the biodegradable system in the regular treatment spectrum of mandibular, Le Fort-I, and zygomatic fractures, and BSSO's, Le Fort-I osteotomies and bimaxillary osteotomies.
Controlled-Trials.com ISRCTN 44212338.
Patients with the genetic blistering skin condition epidermolysis bullosa (EB) report severe pain as a consequence of skin and mucous membrane lesions including blisters, wounds, and scars. Adequate ...symptom alleviation is not often achieved using conventional pharmacologic interventions. Finding novel approaches to pain care in EB is imperative to improve the quality of life of patients living with EB. There are several anecdotal reports on the use of cannabinoid-based medicines (CBMs) by EB patients to reduce the burden of symptoms. However, controlled clinical investigations assessing these reported effects are lacking. As the pain quality "unpleasantness" delineates EB pain, we hypothesize the modulation of affective pain processing in the brain by way of intervention with CBMs comprising the cannabinoids Δ-9-tetrahydrocannabinol and cannabidiol-objectified by functional magnetic resonance imaging (fMRI). The C4EB study is an investigator-initiated, single-centre, randomized, double-blind, placebo-controlled and crossover trial. Adult patients with the diagnosis epidermolysis bullosa, reporting chronic pain will be eligible to participate. Following baseline measurements, participants will be randomized to receive the sublingually administered interventions placebo and Transvamix® in forward or reversed orders, each for two weeks and separated by a washout. The primary outcome is the difference in numeric rating scale pain scores between grouped interventions, using affective descriptors within the Short-form McGill Pain Questionnaire-2. Secondary outcomes include pain self-efficacy, concomitant analgesic medication-use and adverse events. Additionally, fMRI will be employed to assess brain connectivity related to neuroanatomic pain circuits at baseline, placebo and Transvamix® interventions. The study was approved by the ethical committee at the University Medical Center of Groningen in the Netherlands. Results will be submitted for publication in a peer-reviewed journal. Trial registration number: Netherlands Trial Register: NL9347 (Acronym: C4EB).
The trafficking of normal cellular prion protein (PrPC) is believed to control its conversion to the altered conformation (designated PrPSc) associated with prion disease. Although anchored to the ...membrane by means of glycosylphosphatidylinositol (GPI), PrPC on neurons is rapidly and constitutively endocytosed by means of coated pits, a property dependent upon basic amino acids at its N-terminus. Here, we show that low-density lipoprotein receptor-related protein 1 (LRP1), which binds to multiple ligands through basic motifs, associates with PrPC during its endocytosis and is functionally required for this process. Moreover, sustained inhibition of LRP1 levels by siRNA leads to the accumulation of PrPC in biosynthetic compartments, with a concomitant lowering of surface PrPC, suggesting that LRP1 expedites the trafficking of PrPC to the neuronal surface. PrPC and LRP1 can be co-immunoprecipitated from the endoplasmic reticulum in normal neurons. The N-terminal domain of PrPC binds to purified human LRP1 with nanomolar affinity, even in the presence of 1 μM of the LRP-specific chaperone, receptor-associated protein (RAP). Taken together, these data argue that LRP1 controls both the surface, and biosynthetic, trafficking of PrPC in neurons.
The aim of this study was to describe the natural course of pelvic floor symptoms and pelvic floor anatomy for women long-term after hysterectomy.
Women who underwent hysterectomy between 1996-2004 ...carried out the PFDI-20 questionnaire and POP-Q examination. We collected data on the presence and type of pelvic floor symptoms and its relation to the degree of pelvic organ prolapse (POP) per compartment (≥ stage 2).
We obtained data from 247 women on average sixteen years after hysterectomy, with no prolapse (n = 94), anterior prolapse (n = 76), posterior prolapse (n = 38), both anterior- and posterior prolapse (n = 20), and a prolapse involving the vaginal vault (n = 19). Of all 153 women with ≥ stage 2 prolapse, 80 (52%) experienced moderate and/or severe symptoms of the PFDI-20. Most frequently reported symptoms by women with POP were uncontrollable flatus, urinary frequency and urge incontinence. Bulging was associated with a prolapse beyond the hymen. 39% Of women without prolapse experienced bothersome pelvic floor symptoms as well. Most often these were stress incontinence, straining to pass stool and incomplete bowel emptying. Women with a history of hysterectomy for prolapse have more pelvic floor symptoms than women who underwent hysterectomy for other indications, regardless of the current presence of POP (57% versus 40%, p = 0.009).
In a group of post-hysterectomy women who did not actively seek help, 47% experienced problematic pelvic floor symptoms, independent of the presence or absence of an anatomic POP. Creating more knowledge and awareness of the impact of hysterectomy on the pelvic floor can help women in the future.
The study was registered in the Dutch Trial Registry; Trial NL5967 (NTR6333, 2017-02-01) and approved by the Medical Research Ethics Committee of the Máxima Medical Center (NL60096.015.16, 2017-02-24).
The proton sponge hypothesis: Fable or fact? Vermeulen, Lotte M.P.; De Smedt, Stefaan C.; Remaut, Katrien ...
European journal of pharmaceutics and biopharmaceutics,
August 2018, 2018-Aug, 2018-08-00, Letnik:
129
Journal Article
Recenzirano
Odprti dostop
In non-viral gene therapy, cationic polymers and lipids are frequently used to encapsulate macromolecular therapeutics into nanoparticles. During their journey to deliver the cargo to the intended ...intracellular target, many biological barriers need to be overcome. One of the major bottlenecks for efficient transfection is the endosomal barrier since nanoparticles often remain entrapped inside endosomes and are trafficked towards the lysosomes where the cargo is degraded. For cationic polymers, the proton sponge hypothesis was introduced in the late ‘90s as a way to explain their endosomal escape properties. However, to date, no consensus has been reached in the scientific community about the validity of this hypothesis due to many contradictory reports. Here we review the sometimes conflicting reports that have been published on the proton sponge hypothesis. We also discuss membrane destabilization and polymer swelling as additional factors that might influence endosomal escape of polyplexes. Based on the key publications on this subject, we aim to launch a consensus on the role of the proton sponge hypothesis in endosomal escape.
The aim of the study was to examine the relationship between comorbidities and pain, physical function and health-related quality of life (HRQoL) after total hip arthroplasty (THA) and total knee ...arthroplasty (TKA). A cross-sectional retrospective survey was conducted including 19 specific comorbidities, administered in patients who underwent THA or TKA in the previous 7–22 months in one of 4 hospitals. Outcome measures included pain, physical functioning, and HRQoL. Of the 521 patients (281 THA and 240 TKA) included, 449 (86 %) had ≥1 comorbidities. The most frequently reported comorbidities (>15 %) were severe back pain; neck/shoulder pain; elbow, wrist or hand pain; hypertension; incontinence of urine; hearing impairment; vision impairment; and cancer. Only the prevalence of cancer was significantly different between THA (
n
= 38; 14 %) and TKA (
n
= 52; 22 %) (
p
= 0.01). The associations between a higher number of comorbidities and worse outcomes were stronger in THA than in TKA. In multivariate analyses including all comorbidities with a prevalence of >5 %, in THA dizziness in combination with falling and severe back pain, and in TKA dizziness in combination with falling, vision impairments, and elbow, wrist or hand pain was associated with worse outcomes in most of the analyses. A broad range of specific comorbidities needs to be taken into account with the interpretation of patients’ health status after THA and TKA. More research including the ascertainment of comorbidities preoperatively is needed, but it is conceivable that in particular, the presence of dizziness with falling, pain in other joints, and vision impairments should be assessed and treated in order to decrease the chance of an unfavorable outcome.
The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping ...by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology.
Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (< CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel.
QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between < CIN2 and CIN3+ for all markers (p < 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p < 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation> 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified.
The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.
Regular participation in cervical cancer screening is critical to reducing mortality. Although certain sociodemographic factors are known to be associated with one-time participation in screening, ...little is known about other factors that could be related to regular participation. Therefore, this study evaluated the association between health-related behavioral factors and regular participation in cervical cancer screening.
The Lifelines population-based cohort was linked to data for cervical cancer screening from the Dutch Nationwide Pathology Databank. We included women eligible for all four screening rounds between 2000 and 2019, classifying them as regular (4 attendances), irregular (1-3 attendances), and never participants. Multinomial logistic regression was performed to evaluate the association between behavioral factors and participation regularity, with adjustment made for sociodemographic factors.
Of the 48,325 included women, 55.9%, 35.1%, and 9% were regular, irregular, and never screening participants. After adjustment for sociodemographic factors, the likelihood of irregular or never screening participation was increased by smoking, obesity, marginal or inadequate sleep duration, alcohol consumption and low physical activity, while it was decreased by hormonal contraception use.
An association exists between unhealthy behavioral factors and never or irregular participation in cervical cancer screening.
Obsessive and Compulsive Symptoms (OCS) or Obsessive Compulsive Disorder (OCD) in the context of schizophrenia or related disorders are of clinical importance as these are associated with a range of ...adverse outcomes. Natural Language Processing (NLP) applied to Electronic Health Records (EHRs) presents an opportunity to create large datasets to facilitate research in this area. This is a challenging endeavour however, because of the wide range of ways in which these symptoms are recorded, and the overlap of terms used to describe OCS with those used to describe other conditions. We developed an NLP algorithm to extract OCS information from a large mental healthcare EHR data resource at the South London and Maudsley NHS Foundation Trust using its Clinical Record Interactive Search (CRIS) facility. We extracted documents from individuals who had received a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. These text documents, annotated by human coders, were used for developing and refining the NLP algorithm (600 documents) with an additional set reserved for final validation (300 documents). The developed NLP algorithm utilized a rules-based approach to identify each of symptoms associated with OCS, and then combined them to determine the overall number of instances of OCS. After its implementation, the algorithm was shown to identify OCS with a precision and recall (with 95% confidence intervals) of 0.77 (0.65-0.86) and 0.67 (0.55-0.77) respectively. The development of this application demonstrated the potential to extract complex symptomatic data from mental healthcare EHRs using NLP to facilitate further analyses of these clinical symptoms and their relevance for prognosis and intervention response.
We aimed to determine whether children with severe hearing loss (HL) who use hearing aids (HAs) may experience added value in the perception of speech, language development, and executive function ...(EF) compared to children who are hard of hearing (HH) or children who are deaf and who use cochlear implants (CIs) and would benefit from CIs over HAs. The results contribute to the ongoing debate concerning CI criteria. We addressed the following research question to achieve this aim: Do children who are HH or deaf with CIs perform better than children with severe HL with HAs with respect to auditory speech perception, and receptive vocabulary and/or EF?
We compared two groups of children with severe HL, profound HL or deafness, with CIs or HAs, matched for gender, test age (range, 8 to 15 years), socioeconomic status, and nonverbal intelligence quotient. Forty-three children had CIs (pure-tone average at 2000 and 4000 Hz >85 dB HL), and 27 children had HAs (mean pure-tone average: 69 dB HL). We measured speech perception at the conversational level (65 dB SPL) and the soft speech perception level (45 dB SPL). We established receptive vocabulary using the Peabody Picture Vocabulary Test-III-NL. We tested EF using the Delis Kaplan Executive Function System battery and the Dutch Rey Auditory Verbal Learning Test. We employed the Mann-Whitney U test to compare data between the CI and HA groups. We used Chi-square goodness of fit tests to contrast the CI and HA group distributions with the norm data of children who are typically developing (TD). We harnessed Kendall's Tau-b to investigate relationships between the study variables.
Both groups of children, with CIs and Has, obtained ceiling scores for perception of speech on a conversational level. However, the HA group exhibited significantly lower perception on a soft speech level scores (68 %) than the CI group (87%). No difference was present between the receptive vocabulary distributions of the CI and HA groups. The median receptive vocabulary standard scores for both groups were well within the normal range (CI group: 93; HA group: 96). In addition, we did not find any difference in EF between the CI and HA groups. For planning and verbal memory, the distributions of observed scores for children with CIs were different from the expected distributions of children who are TD. In both groups, a large proportion of children obtained below-average scores for planning (CI: 44%; HA: 33%) and for long-term verbal memory (CI: 44%; HA: 35%). In the HA group, perception at a soft speech level was associated with receptive vocabulary and planning. In the CI group, we did not find any associations.
Both groups of children with severe and profound HL with HAs exhibit less favorable auditory perception on the soft speech level, but not at a conversational level, compared to children who are HH or deaf with CIs. Both groups, children with CIs and HAs, only exhibit more problems in planning and verbal memory than the norm groups of children who are TD. The results indicate that to obtain age-appropriate levels of receptive vocabulary and EF, the perception at the soft speech level is a necessary but not sufficient prerequisite.
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