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Background: Culturally sensitive care is integral to effective and equitable healthcare delivery, necessitating an understanding and acknowledgment of patients' cultural needs, preferences, and expectations. This study investigates the perceptions of cultural sensitivity among general practitioners (GPs), focusing on their intentions, willingness and perceived responsibilities in providing care tailored to cultural needs. Methods: In-depth interviews were conducted with 21 Flemish GPs to explore their perspectives on culturally sensitive care. Data analysis followed a conventional qualitative content analysis approach within a constructivist framework. A coding scheme was developed to identify recurring themes and patterns in the GPs' responses. Results: Findings reveal that culturally sensitive care provision is perceived as a multifaceted process, initiated by an exploration phase where GPs inquire about patients' cultural needs and preferences. Two pivotal factors shaping culturally sensitive care emerged: patients' specific cultural expectations and GPs' perceived responsibilities. These factors guided the process of culturally sensitive care towards three distinct outcomes, ranging from complete adaptation to patients' cultural requirements driven by a high sense of responsibility, through negotiation and compromise, to a paternalistic approach where GPs expect patients to conform to GPs' values and expectations. Three typologies of GPs in providing culturally sensitive care were identified: genuinely culturally sensitive, surface-level culturally sensitive, and those perceiving diversity as a threat. Stereotyping and othering persist in healthcare, underscoring the importance of critical consciousness and cultural reflexivity in providing patient-centered and equitable care. Conclusions: This study emphasizes the significance of empathy and underscores the necessity for GPs to embrace the exploration and acknowledgement of patients' preferences and cultural needs as integral aspects of their professional role. It highlights the importance of shared decision-making, critical consciousness, cultural desire and empathy. Understanding these nuances is essential for enhancing culturally sensitive care and mitigating healthcare disparities. [ABSTRACT FROM AUTHOR]

Summary: The bendamustine–rituximab (BR) schedule is an efficient first‐line therapy in Waldenström macroglobulinaemia (WM). A previous analysis of 69 patients who received this treatment confirmed a high response rate and good progression‐free (PFS) and overall survival (OS). With a median follow‐up of 76.1 months (95% confidence interval [CI] 69.9–80.6), 5‐year outcome is still excellent at 66.63% (95% CI 56.09–79.17) for PFS and 80.01% (95% CI 70.82–90.41) for OS. The rate of secondary cancers is 17.66% (IQR 7.99–27.64) at 66 months. Relapsed patients who received ibrutinib as second‐line clearly benefited from this schedule. This confirms current recommendations suggesting BR long‐term efficacy as first‐line option in WM. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 42-year-old patient experiencing foot pain, a 65-year-old man with diabetic neuropathy, and a 62-year-old man with chronic obstructive pulmonary disease, discussing treatment options, diagnostic techniques, and lifestyle interventions for each condition. Topics discussed include managing plantar fasciitis, diagnosing arthritis in the foot and ankle, and incorporating exercise for patients with chronic lung disease.

Keywords: osteoporosis; patient preference; burden of disease; quality of life EN osteoporosis patient preference burden of disease quality of life 107 118 12 02/08/23 20230101 NES 230101 Kyriakos Souliotis, SP 1, sp SP 2 sp Christina Golna, SP 2 sp Christina Poimenidou, SP 2 sp Tatiana Drakopoulou, SP 3 sp Memi Tsekoura, SP 2 sp Damon Willems, SP 4 sp Vasileios Kountouris, SP 5 sp Polyzois Makras SP 6 sp SP 1 sp Department of Social and Education Policy, University of Peloponnese, Corinth, Greece; SP 2 sp Research Department, Health Policy Institute, Maroussi, Greece; SP 3 sp Greek Bone Health Association "Petalouda", Perama, Greece; SP 4 sp Market Access Lead, UCB Pharma, Brussels, Belgium; SP 5 sp External Engagement Lead, UCB Pharma, Athens, Greece; SP 6 sp Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece Correspondence: Kyriakos Souliotis, Email [email protected] Plain Language Summary This study aimed to describe patient-reported health status and quality of life in postmenopausal women with severe osteoporosis in Greece, and to understand patient preferences for osteoporosis therapies. Finally, when participants in this study were asked to select their preferred treatment scenario between two unlabeled anabolic treatments, 70% opted for the scenario that shared treatment characteristics with romosozumab over a scenario that shared treatment characteristics with teriparatide. Around half of participants (58%) would consider their osteoporosis treatment to be effective if it led to a 50% reduction in future fracture risk, 10% would consider their osteoporosis treatment to be effective only if it led to an 80% reduction in risk, and almost 20% only if it led to at least a 90% reduction in risk. [Extracted from the article]

Internalized HIV stigma is prevalent and research on internalized HIV stigma has increased during the past 10 years. The aim of this systematic review was to synthesize research on internalized HIV stigma and relationships with various health-related variables in order to better inform the development of interventions aimed at reducing internalized HIV stigma. We reviewed 176 studies with a quantitative design reporting correlates that were peer-reviewed, published in English before January 2021, drawn from PubMed, PSYCHINFO, Web of Science, EBSCO, and Scopus. Synthesis showed consistent associations between internalized stigma and negative psychological (e.g., depression, anxiety), social (e.g., lack of social support, discrimination, nondisclosure, and intersecting stigmas), and health (e.g., substance use, treatment nonadherence, negative clinical HIV outcomes) variables. We argue for a more socioecological approach to internalized stigma, with greater attention for intersectional stigmas, and more longitudinal research, if we are to effectively develop interventions that reduce internalized stigma. [ABSTRACT FROM AUTHOR]

Introduction: For pediatric dentistry and orthodontists it is extremely important to estimate age in treatment planning. Basis of treatment planning of skeletal disharmonies is optimal treatment time. The most favorable time for the treatment of skeletal disharmonies is before or during pubertal growth spurt. As there are individual variation in the beginning and duration of pubertal growth acceleration we need an assessment of individual development stages. Aim: The aim of this study was to examine the relationship between chronological and dental age estimated on the basis of the method according to Demirjian, according to Willems and to Cameriere respectively. Materials and Methods: Retrospective study was performed on a sample of 560 orthodontics patients aging from 7.83 - 15.08, mean age being 11.62 (255 boys mean age 11.57 and 305 girls mean age 11.66). Dental age from panoramic radiographs was assessed using Demirjian method (mean age 12,64), Willems method (mean age 12,07) and Camerieri method (mean age 11.47). Results: By establishing the connection between those three methods of dental age assessment and chronological age of the respondents it is confirmed a statistically significant correlation with the achieved high coefficients of determination (r 2). Correlation of chronological age, common variation (determinative coefficient), achieved with Demirjian dental age was r2 = 0.867, followed by Cameriere dental age r2 = 0.863 and with Willems dental age r2 = 0.854. Correlation refers analyzed variables are presented in diagram. Conclusion: The greatest correlation of chronological age was achieved with Demirjian dental age (r2 = 0.867). [ABSTRACT FROM AUTHOR]

Bovine leukemia virus (BLV) is a retrovirus closely related to the human T-lymphotropic virus type 1 (HTLV-1). BLV is a major animal health problem worldwide causing important economic losses. A series of attempts were developed to reduce prevalence, chiefly by eradication of infected cattle, segregation of BLV-free animals and vaccination. Although having been instrumental in regions such as the EU, these strategies were unsuccessful elsewhere mainly due to economic costs, management restrictions and lack of an efficient vaccine. This review, which summarizes the different attempts previously developed to decrease seroprevalence of BLV, may be informative for management of HTLV-1 infection. We also propose a new approach based on competitive infection with virus deletants aiming at reducing proviral loads.

Oncology and hematology physicians aim during the COVID-19 pandemic to protect their patients from COVID-19 infection without impairing the prognosis of the disease. We describe how at-home treatment was used in our department to maintain multiple myeloma treatment while protecting the patient. [Extracted from the article]

Aim The purpose of this study was to evaluate the periapical status of endodontically treated teeth and the integrity of endodontic treatment before and after orthodontic treatment. Materials and methods This retrospective study was conducted by evaluating 128 teeth with root canal treatment (RCT). The teeth were obtained from 72 patients (23 males, 49 females) who had undergone fixed orthodontic treatment. Panoramic radiographs were taken and were evaluated before the start and after the completion of orthodontic treatment. Apical periodontitis (AP) was evaluated by the periapical index (PAI) and the probability index (PRI) of periapical bone destruction. Other variables related to the quality of root canal fillings were included, such as RCT quality index, length, and homogeneity, and coronal restoration. Results According to the PRI, the proportion of teeth with periapical bone destruction was significantly higher after orthodontic treatment. Overall, there was no significant change in the PAI scores after orthodontic treatment. However, the quality of the endodontic treatment moderated the change in the PAI score, as well as the change in the PRI. There was no significant increase in PAI and PRI scores after orthodontic treatment for adequately treated teeth. However, the risk for periapical lesions and bone destruction after orthodontic treatment was significantly increased for teeth receiving inadequate endodontic treatment compared with those receiving adequate endodontic treatment. Conclusion Increased PAI and PRI after orthodontic treatment correlated with the quality of endodontic treatment. [ABSTRACT FROM AUTHOR]

Background: An important goal in the treatment of osteoporotic vertebral compression fractures (OVCFs) is the prevention of new vertebral fractures and the subsequent progression to global sagittal malalignment. Current conservative treatment is multimodal and comprises analgesics, medication for osteoporosis, and physical therapy. However, little is known about the value of orthoses in the treatment of OVCFs. Aims: The primary purpose of this study was to examine the direct effect of a semirigid thoracolumbar orthosis on gait in patients suffering from an OVCF. The secondary purpose was to evaluate changes in gait, radiographic sagittal alignment, pain, and quality of life over time. Methods: Fifteen postmenopausal patients with an OVCF were treated with a semirigid thoracolumbar orthosis. At baseline, after 6 weeks, and after 6 months, gait analysis was performed with a dual belt–instrumented treadmill with a 180° projection screen providing a virtual environment (computer-assisted rehabilitation environment) combined with clinical and radiographic assessments. Results: At baseline, bracing caused a significantly more upright posture during walking and patients walked faster, with larger strides, longer stride times, and lower cadence compared to walking without orthosis. After 6 weeks, radiographic and dynamic sagittal alignment had improved compared to baseline. The observed effect was gone after 6 months, when the orthosis was not worn anymore. Conclusion: A semirigid thoracolumbar orthosis seems to have a positive effect on gait and stability in patients suffering from an OVCF, as was shown by a more upright posture, which may result in decreased compressive loading of the vertebrae. For studying the true effectiveness of dynamic bracing in the treatment of OVCFs, a prospective, randomized controlled trial will be needed. [ABSTRACT FROM AUTHOR]

Introduction: The MARVEL study demonstrated at a single time point that accelerometer (ACC)‐based atrial sensing improves atrioventricular (AV) synchrony (AVS) in patients with AV block and a Micra pacemaker (Medtronic, Minneapolis, MN, USA). The purpose of the MARVEL Evolve substudy was to assess the performance over time. Methods: This prospective single‐center study compared AVS and ACC signals at two visits ≥6 months apart. Custom software was temporarily downloaded into the Micra at each visit and AVS was measured during 30 min at rest. Results: Nine patients from the MARVEL study were enrolled. The mean (±standard deviation) age was 82.3 ± 6.0 years old, 67% were male, and a Micra was implanted for 6.0 ± 6.4 months. High‐degree AV block was present in four patients, whereas five with predominantly intrinsic conduction required intermittent pacing for bradycardia. The mean interval between visits was 7.1 ± 0.6 months. Seven patients had normal sinus node function at both visits and were included in a paired analysis. Both ACC signal amplitude (visit 2‐visit 1 = 1.4 mG; 95% confidence interval [CI] [−25.8 to 28.4 mG]; P = 0.933) and AVS (visit 1: 90.8%, 95% CI [72.4, 97.4] and visit 2: 91.4%, 95% CI [63.8, 98.5]; P = 0.740) remained stable. Three patients had spontaneous atrial tachycardia. During atrial fibrillation, no atrial contraction was detected or tracked. During atrial flutter, intermittent tracking resulted in a ventricular rate of 60 ± 8 beats per minute (bpm); there was no ventricular pacing >100 bpm. Conclusion: ACC signals amplitude and performance of AVS pacing were stable over time. During atrial arrhythmias, the AV synchronous pacing mode behaved safely. [ABSTRACT FROM AUTHOR]

Background: Promotion of a healthy lifestyle for people with intellectual disabilities is important; however, the effectiveness of lifestyle change interventions is unclear. Aims: This research will examine the effectiveness of lifestyle change interventions for people with intellectual disabilities. Methods and Procedures: Randomized controlled trials (RCTs) of lifestyle change interventions for people with intellectual disabilities were included in a systematic review and meta‐analysis. Data on study and intervention characteristics were extracted, as well as data on outcome measures and results. Internal validity of the selected papers was assessed using the Cochrane Collaboration's risk bias tool. Outcomes and Results: Eight RCTs were included. Multiple outcome measures were used, whereby outcome measures targeting environmental factors and participation were lacking and personal outcome measures were mostly used by a single study. Risks of bias were found for all studies. Meta‐analysis showed some effectiveness for lifestyle change interventions, and a statistically significant decrease was found for waist circumference. Conclusion and Implications: Some effectiveness was found for lifestyle change interventions for people with intellectual disabilities. However, the effects were only statistically significant for waist circumference, so current lifestyle change interventions may not be optimally tailored to meet the needs of people with intellectual disabilities. [ABSTRACT FROM AUTHOR]

Objective: To systematically and comprehensively document the effectiveness of nonpharmacologic interventions on physical functioning and psychological well-being in patients with systemic sclerosis (SSc).Methods: Multiple electronic databases were searched for studies on the effectiveness of nonpharmacologic interventions in SSc. Randomized clinical trials (RCTs), controlled clinical trials (CCTs), and observational designs (ODs) with ≥10 participants were included. Two reviewers independently assessed methodologic quality using the Downs and Black checklist.Results: Twenty-three studies (9 RCTs, 4 CCTs, and 10 ODs) were included. Studies assessing comparable interventions were grouped, resulting in data for 16 different interventions. The total number of patients included per study ranged from 10 to 53. Seventeen different outcome domains were assessed, with hand function, limitations in activities, and quality of life being assessed most frequently. Three studies, all RCTs, were rated as high quality. These RCTs reported that 1) a multifaceted oral health intervention improves mouth hygiene, and additional orofacial exercises did not improve mouth opening, 2) a multidisciplinary team-care program improves limitations in activities, mouth opening, and hand grip strength, and 3) manual lymph drainage improves hand function, limitations in activities, and quality of life.Conclusion: The body of knowledge regarding nonpharmacologic care in SSc is very limited due to the wide variety in studied interventions and outcomes in the relatively uncommon but highly disabling disease. To structure and focus future research, an international consensus should be established to prioritize primary targets for nonpharmacologic treatment and the content of interventions and to agree on a core set of outcome measures. [ABSTRACT FROM AUTHOR]

Whether well-being and depressive symptoms can be considered as two sides of the same coin is widely debated. The aim of this study was to gain insight into the etiology of the association between well-being and depressive symptoms across the lifespan. In a large twin-design, including data from 43,427 twins between age 7 and 99, we estimated the association between well-being and depressive symptoms throughout the lifespan and assessed genetic and environmental contributions to the observed overlap. For both well-being (range 31–47%) and depressive symptoms (range 49–61%), genetic factors explained a substantial part of the phenotypic variance across the lifespan. Phenotypic correlations between well-being and depressive symptoms across ages ranged from −0.34 in childhood to −0.49 in adulthood. In children, genetic effects explained 49% of the phenotypic correlation while in adolescents and young adults, genetic effects explained 60–77% of the phenotypic correlations. Moderate to high genetic correlations (ranging from −0.59 to −0.66) were observed in adolescence and adulthood, while in childhood environmental correlations were substantial but genetic correlations small. Our results suggest that in childhood genetic and environmental effects are about equally important in explaining the relationship between well-being and depressive symptoms. From adolescence onwards, the role of genetic effects increases compared to environmental effects. These results provided more insights into the etiological underpinnings of well-being and depressive symptoms, possibly allowing to articulate better strategies for health promotion and resource allocation in the future. [ABSTRACT FROM AUTHOR]

Background: Several case reports and small case series have suggested a higher incidence of medication-related osteonecrosis of the jaw (MRONJ) in patients treated concomitantly with bone resorption inhibitors (BRIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), as compared to patients treated with BRIs alone. We aimed to assess ONJ-incidence in patients exposed concomitantly to BRIs and VEGFR-TKIs.Patients and Methods: We reviewed the records of all patients who received VEGFR-TKIs concomitantly with BRIs. Patients, who were treated with BRIs without VEGFR-TKI, served as a control group. Endpoints of the study were total MRONJ-incidence, MRONJ-incidence during the first and second year of exposure, and time-to-ONJ-incidence.Results: Ninety patients were treated concomitantly with BRIs and VEGFR-TKIs with a median BRI-exposure of 5.0 months. Total MRONJ-incidence was 11.1%. During the first year of BRI-exposure (with a median concomitant exposure of 4.0 months), 6 out of 90 patients (6.7%) developed a MRONJ, compared to 1.1% in the control group (odds ratio 5.9; 95%CI 2.0-18.0; p = 0.0035). In Kaplan-Meier estimates, time-to-ONJ-incidence was significantly shorter in patients treated with BRIs and VEGFR-TKIs compared to BRIs alone (hazard ratio 9.5; 95%CI 3.1-29.6; p < 0.0001). MRONJs occurred earlier in patients treated concomitantly compared to patients treated with BRIs only (after a median exposure of 4.5 and 25.0 months, respectively; p = 0.0033).Conclusion: With a global MRONJ-incidence of 11%, patients receiving concomitant treatment with VEGFR-TKIs and BRIs have a five to ten times higher risk for development of MRONJ compared to patients treated with BRIs alone. [ABSTRACT FROM AUTHOR]

Background: The use of low intra-abdominal pressure (<10 mmHg) reduces postoperative pain scores after laparoscopic surgery. Objective: To investigate whether low-pressure pneumoperitoneum with deep neuromuscular blockade improves the quality of recovery after laparoscopic donor nephrectomy (LDN). Design, setting and participants: In a single-center randomized controlled trial, 64 live kidney donors were randomly assigned to 6 or 12 mmHg insufflation pressure. A deep neuromuscular block was used in both groups. Surgical conditions were rated by the five-point Leiden-surgical rating scale (L-SRS), ranging from 5 (optimal) to 1 (extremely poor) conditions. If the L-SRS was insufficient, the pressure was increased stepwise. Main outcome measure: The primary outcome measure was the overall score on the quality of recovery-40 (QOR-40) questionnaire at postoperative day 1. Results: The difference in the QOR-40 scores on day 1 between the low- and standard-pressure group was not significant ( p = .06). Also the overall pain scores and analgesic consumption did not differ. Eight procedures (24%), initially started with low pressure, were converted to a standard pressure (≥10 mmHg). A L-SRS score of 5 was significantly more prevalent in the standard pressure as compared to the low-pressure group at 30 min after insufflation ( p < .01). Conclusions: Low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade during LDN does not reduce postoperative pain scores nor improve the quality of recovery in the early postoperative phase. The question whether the use of deep neuromuscular blockade during laparoscopic surgery reduces postoperative pain scores independent of the intra-abdominal pressure should be pursued in future studies. Trial registration: The trial was registered at clinicaltrial.gov before the start of the trial (NCT02146417). [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma (AdCC) of the head and neck is an uncommon malignant epithelial tumour of the secretory glands. Many patients develop slowly growing local recurrence and/or distant metastasis, for which treatment options are limited. A retrospective analysis of 9 AdCC patients was conducted to analyse the visualization of AdCC on PSMA PET/CT and to investigate the expression of PSMA on primary, recurrent and metastatic AdCC tumour tissue using immunohistochemistry. Results: Local recurrence occurred in six patients and eight developed distant metastasis. All PET/CTs depicted PSMA-ligand uptake. Four PSMA PET/CTs showed suspected residual disease, eight scans depicted uptake in areas suspected of distant metastasis. Median Maximum Standardized Uptake Value (SUV) in local recurrent and distant metastatic AdCC was 2.52 (IQR 2.41-5.95) and 4.01 (IQR 2.66-8.71), respectively. All primary tumours showed PSMA expression on immunohistochemistry (5-90% expression), as well as all available specimens of local recurrence and distant metastases. Conclusion: PSMA PET/CT is able to detect and visualize local recurrent and distant metastatic AdCC. PSMA-specific targeting is supported by PSMA expression on immunohistochemistry. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effects of orthodontic non-extraction treatment with or without headgear on the position of and the space available for upper third molars in growing children with class II malocclusions. Materials and methods: The sample consisted of pre- and post-treatment panoramic radiographs and lateral cephalograms of 294 class II orthodontic patients; 160 were treated with headgear and 134 were treated without headgear. The space available for the upper third molar was measured on the lateral cephalogram as the distance from pterygoid vertical (PTV) to the distal surface of the upper first molar crown (PTV-M1). Angulation, vertical position and tooth development stage of the upper third molars were evaluated on panoramic radiographs. All measurements were evaluated statistically. Results: In both groups PTV-M1 increased, but the increase in PTV-M1 was significantly higher for patients treated without headgear. A linear model for repeated measures revealed that this difference was still significant after correction for age, gender and molar occlusion. Further, there is no evidence that the change in angulation, vertical position and development stage of the upper third molars during orthodontic treatment is influenced by headgear therapy. Conclusion: This study indicates that the use of headgear in growing patients significantly affects the space available for upper third molars. However, orthodontic treatment with headgear does not influence the angulation, vertical position and development stage of upper third molars. It is therefore important to always take into account third molars during treatment planning. [ABSTRACT FROM AUTHOR]

The article focuses on problem of concussion in professional sports litigation with advancements in medicine and lawyers need to understand some of the basics of concussion diagnosis and treatment and legal developments. Topics discussed include need to determine an athlete's cognitive abilities and identify underlying health conditions, legal claims available to help compensate a concussed athlete such as negligence, fraud and product liability and issues regarding statutory immunities.

Background There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. Methods All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. Results We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). Conclusion In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local recurrence. Therefore, we suggest (neo-)adjuvant chemotherapy in patients amenable to chemotherapy. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 39: 140-146, 2017 [ABSTRACT FROM AUTHOR]

Objective IQSEC2 is an X-linked gene associated with intellectual disability ( ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. Methods Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. Results Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic ( GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging ( MRI) were prominent features. Significance The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC2 should be evaluated in both male and female patients with an epileptic encephalopathy. [ABSTRACT FROM AUTHOR]

Different follow-up methods have been used to report success rates after AF ablation. Recent studies have shown that intermittent rhythm monitoring underestimates the actual AF recurrence rate. We therefore report our experience with continuous rhythm monitoring by implantable loop recorder (ILR) in a large patient cohort. Between 09/2008 and 12/2012, 343 cardiac surgical patients underwent concomitant surgical AF ablation. ILR implantation was performed in 206 patients. ILR interrogation was accomplished at 3, 6 and 12 months postoperatively. Successful ablation was defined as AF Burden <0.5 %. Primary outcome of the study was freedom from AF at 12-month follow-up. Mean patient's age was 70.5 ± 7.4 years. No major ablation- or ILR-related complications occurred. In 4 patients (1.9 %) ILR had to be explanted due to ILR-related wound infection ( n = 2) or chronic pain ( n = 2). Survival rate at 1-year follow-up was 96.6 %. Freedom from AF rate after 1-year follow-up was 68.5 and 63.6 % off antiarrhythmic drugs, respectively. Statistically significant predictors for successful ablation at 1-year follow-up were smaller LA diameter, shorter duration of AF and preoperative paroxysmal AF. Demographic data, indication for surgery, lesion set and used energy source had no impact on freedom from AF after 1 year. Continuous ILR monitoring after concomitant surgical AF ablation was safe and feasible, with registered freedom from AF rate of 68.5 % at 1-year follow-up. Thus continuous rhythm monitoring provides reliable outcome data and helps to guide antiarrhythmic therapy. [ABSTRACT FROM AUTHOR]

Background: Lumbar spinal fusion for degenerative disorders of the lumbar spine is frequently used, despite current research presenting inconclusive evidence. This study aims to systematically review and meta-analyse the natural course of pain and disability in patients with degenerative disorders of the lumbar spine such as spinal stenosis, spondylolisthesis, disc herniation, or discogenic low back pain to improve lumbar spinal fusion management. Methods/design: An electronic database search will be conducted up to 30 September 2015 using MEDLINE, EMBASE, CINAHL, and ZETOC database. In addition, a search for articles in press and published ahead of print, British National Bibliography for Report Literature, and OpenGrey will be conducted. Prospective cohort studies using outcome measures of pain and disability will be eligible for inclusion. Two reviewers will screen titles, abstracts, and full-text independently using predetermined inclusion and exclusion criteria. The risk of bias of included studies will be assessed with the modified version of the Quality in Prognostic Studies tool. If metaanalysis of outcome data is deemed appropriate, variance-weighted pooled means will be calculated. Discussion: The results of this systematic review and meta-analysis may improve understanding of recovery after lumbar spinal fusion and improve lumbar spinal fusion management. [ABSTRACT FROM AUTHOR]

Chorioamnionitis, an inflammatory reaction of the fetal membranes to microbes, is an important cause of preterm birth and associated with inflammation-driven lung injury. However, inflammation in utero overcomes immaturity of the premature lung by inducing surfactant lipids and lung gas volume. Previously, we found that lipopolysaccharide (LPS)-induced chorioamnionitis resulted in pulmonary inflammation with increased effector T cells and decreased regulatory T cell (Treg) numbers. Because Tregs are crucial for immune regulation, we assessed the effects of interleukin (IL)-2-driven selective Treg expansion on the fetal lung in an ovine chorioamnionitis model. Instrumented fetuses received systemic prophylactic IL-2 treatment [118 days gestational age (dGA)] with or without subsequent exposure to intra-amniotic LPS (122 dGA). Following delivery at 129 dGA (term 147 dGA), pulmonary and systemic inflammation, morphological changes, lung gas volume, and phospholipid concentration were assessed. IL-2 pretreatment increased the FoxP3+/CD3+ ratio, which was associated with reduced CD3-positive cells in the fetal lungs of LPS-exposed animals. Prophylactic IL-2 treatment did not prevent pulmonary accumulation of myeloperoxidase- and PU.1-positive cells or elevation of bronchoalveolar lavage fluid IL-8 and systemic IL-6 concentrations in LPS-exposed animals. Unexpectedly, IL-2 treatment improved fetal lung function of control lambs as indicated by increased disaturated phospholipids and improved lung gas volume. In conclusion, systemic IL-2 treatment in utero preferentially expanded Tregs and improved lung gas volume and disaturated phospholipids. These beneficial effects on lung function were maintained despite the moderate immunomodulatory effects of prophylactic IL-2 in the course of chorioamnionitis. [ABSTRACT FROM AUTHOR]

Background: Degenerative lumbosacral stenosis is a common problem in large breed dogs. For severe degenerative lumbosacral stenosis, conservative treatment is often not effective and surgical intervention remains as the last treatment option. The objective of this retrospective study was to assess the middle to long term outcome of treatment of severe degenerative lumbosacral stenosis with pedicle screw-rod fixation with or without evidence of radiological discospondylitis. Results: Twelve client-owned dogs with severe degenerative lumbosacral stenosis underwent pedicle screw-rod fixation of the lumbosacral junction. During long term follow-up, dogs were monitored by clinical evaluation, diagnostic imaging, force plate analysis, and by using questionnaires to owners. Clinical evaluation, force plate data, and responses to questionnaires completed by the owners showed resolution (n=8) or improvement (n = 4) of clinical signs after pedicle screw-rod fixation in 12 dogs. There were no implant failures, however, no interbody vertebral bone fusion of the lumbosacral junction was observed in the follow-up period. Four dogs developed mild recurrent low back pain that could easily be controlled by pain medication and an altered exercise regime. Conclusions: Pedicle screw-rod fixation offers a surgical treatment option for large breed dogs with severe degenerative lumbosacral stenosis with or without evidence of radiological discospondylitis in which no other treatment is available. Pedicle screw-rod fixation alone does not result in interbody vertebral bone fusion between L7 and S1. [ABSTRACT FROM AUTHOR]

Background: Concomitant Surgical AF ablation is an established procedure, recommended in guidelines. However many surgeons are reluctant to perform AF ablation in patients with significantly enlarged left atrium. We therefore analyzed outcomes of patients with left-atrial diameter >55 mm undergoing concomitant AF ablation.Methods: Between 05/2003 and 12/2012 124 patients with significantly enlarged left-atrium >55 mm underwent concomitant surgical AF ablation. Rhythm monitoring was accomplished by implantable loop recorder (ILR) interrogation (n = 54), or 24-h Holter-ECG (n = 70). Successful ablation was defined as AF Burden <0.5 % in ILR interrogation or absence of AF episode >30 s in 24-h Holter-ECG. Primary endpoint of the study was freedom from AF at 12 months follow-up.Results: Mean patient's age was 65.7+/-9.6 years, 69.4 % were male. No major ablation or ILR related complications occurred. Mean LA diameter was 60.7+/-4.4 mm. Survival rate at one-year follow up was 94.4 %. 11 (8.8 %) patients received additional catheter-based ablation, while 23 (18.5 %) had an electrical cardioversion during follow-up period. Overall freedom from AF rate after one-year follow-up was 64.4 % and 59.4 % off antiarrhythmic drugs respectively. Logistic regression analysis identified preoperative paroxysmal AF, duration of AF and LA diameter > 70 mm as predictors for rhythm outcome at 12 months follow-up.Conclusion: In this patient cohort with significantly enlarged LA diameter, concomitant surgical AF ablation provided freedom from AF of 64.4 % after one-year follow-up. However in this patient population, an accurate postoperative care with interventions like medical or- electrical cardioversion and additional catheter based ablation is necessary to achieve satisfactory results. [ABSTRACT FROM AUTHOR]

Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 induced Adult T cell leukemia (ATL). The paper by Zane et al. shows that a mediator of p53 activity, Wild-type p53-induced phosphatase 1 (Wip1), contributes to Tax-induced oncogenesis in a mouse model. Wip1 may therefore be a novel target for therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: More and more quantitative information is becoming available about the risks of complications arising from medical treatment. In everyday practice, this raises the question whether each and every risk, however low, should be disclosed to patients. What could be good reasons for doing or not doing so? This will increasingly become a dilemma for practitioners. Objective: To report doctors' views on whether to disclose or withhold information on low risks of complications. Methods: In a qualitative study design, 37 respondents (gastroenterologists and gynaecologists or obstetricians) were included. Focus group interviews were held with 22 respondents and individual in-depth interviews with 15. Results: Doctors have doubts about disclosing or withholding information on complication risk, especially in a risk range of 1 in 200 to 1 in 10 000. Their considerations on whether to disclose or to withhold information depend on a complicated mix of patient and doctor-associated reasons; on medical and personal considerations; and on the kind and purpose of intervention. Discussion: Even though the degree of a risk is important in a doctor's considerations, the severity of the possible complications and patients' wishes and competencies have an important role as well. Respondents said that low risks should always be communicated when there are alternatives for the intervention or when the patient may prevent or mitigate the risk. When the appropriateness of disclosing risks is doubtful, doctors should always tell their patients that no intervention is without risk, give them the opportunity to gather all the information they need or want, and enable them to detect a complication at an early stage. [ABSTRACT FROM AUTHOR]

Objective: The most recent WHO definition of palliative care regards living as actively as possible as an important aim. We explored, over a 1-year period, the work this involves for patients with end-stage heart failure. Design: Prospective longitudinal multiple case study using qualitative interview techniques. Participants: Thirty-one respondents from two hospitals who fulfilled one or more of the following criteria: NYHA III or IV, ejection fraction < 25%, at least one hospitalization for heart failure. Main outcomes: Types and content of patient work involved in living with end-stage heart failure. Results: For patients with advanced heart failure, work consisted mainly of four types of tasks, as identified by Glaser and Strauss: 'managing illness', 'everyday work to keep life going', 'biographical work' and 'arrangement work'. Conclusions: Systematic attention to patient work, for example using these four categories, could improve the quality of care from the patient's perspective. [ABSTRACT FROM AUTHOR]

Arterial coronary bypass grafts [internal mammary arteries and gastroepiploic artery (GEA)] are in widespread use for coronary surgery. Since selective catheterisation of the GEA graft to monitor patency, is often unsuccessful, a non-invasive protocol to visualise the GEA-graft from origin to anastomosis is presented using 16-slice multidetector computed tomography (MDCT). Twenty-six male patients (mean age 58.1+/-6.7 years) with GEA grafts were scanned according to a protocol of an ECG-synchronised cardiac scan followed by a thoracoabdominal scan. To terminate the scan at the correct anatomical level, the lowest level of the GEA was coded based on the lumbar vertebrae level. Scores ranging from one (excellent) to four (bad) were assigned to evaluate visualisation quality of the grafts. GEA grafts were assessable in 62% of the thoracoabdominal scans and 69% of the cardiac scans. On average, the lowest part of the GEA corresponded with a level between L1 and L2, in two cases in the upper part of L3. Mean visualisation score in the thoracoabdominal scans and cardiac scans was good (respectively 1.4+/-0.6 and 1.4+/-1.0). Sixteen-slice MDCT is a promising alternative for catheterisation in evaluating patency of GEA grafts, using the presented protocol with thoracoabdominal scan including L3 for complete coverage of the GEA graft. [ABSTRACT FROM AUTHOR]

Two strains of porcine reproductive and respiratory syndrome virus (PRRS V) were isolated in 2006 and 2016 and designated as FZ06A and FZ16A, respectively. Inoculation experiments showed that FZ06A caused 100% morbidity and 60% mortality, while FZ16A caused 100% morbidity without death. By using genomic sequence and phylogenetic analyses, close relationships between a Chinese highly pathogenic PRRS V strain and the FZ06A and FZ16A strains were observed. Based on the achieved results, multiple genomic variations in Nsp2, a unique N-glycosylation site (N33--»K33), and a K151 amino acid (AA) substitution for virulence in the GP5 of FZ16A were detected; except the 30 AA deletion in the Nsp2-coding region. Inoculation experiments were conducted and weaker virulence of FZ16A than FZ06A was observed. Based on our results, a 30 AA deletion in the Nsp2-coding region is an unreliable genomic indicator of a high virulence PRRSV strain. The Nsp2 and GP5 differences, in addition to the virulence difference between these two highly pathogenic PRRSV strains, have the potential to be used to establish a basis for further study of PRRSV virulence determinants and to provide data useful in the development of vaccines against this economically devastating disease. [ABSTRACT FROM AUTHOR]

Background: The approach to treat device infection in patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) is a challenging procedure. Optimal treatment is complete extraction of the infected device. To protect these patients from sudden cardiac arrest while waiting for reimplantation and to avoid recurrent infection, a wearable cardioverter defibrillator (WCD) seems to be a valuable solution. Therefore, we investigated the management and outcome of patients with ICD or CRT-D infections using the WCD as a bridge to re-implantation after lead extraction procedures.Methods: We conducted a retrospective study on consecutive patients who underwent ICD or CRT-D removal due to device-related local or systemic infections. All patients were prescribed a WCD at our center between 01/2012 and 10/2015. All patients returned to our outpatient clinic for regular ICD or CRT-D monitoring initially 1 and 3 months after reimplantation followed by 6-months intervals.Results: Twenty-one patients (mean age 65.0 ± 8.0 years, male 76.2%) were included in the study. Complete lead extraction was achieved in all patients. While waiting for reimplantation one patient experienced a symptomatic episode of sustained ventricular tachycardia. This episode was converted successfully into sinus rhythm by a single 150 J shock. Mean follow-up time 392 ± 206 days, showing survival rate of 100% and freedom from reinfection in all patients.Conclusion: The WCD seems to be a valuable bridging option for patients with ICD or CRT-D infections, showing no recurrent device infection. [ABSTRACT FROM AUTHOR]

Background Schnitzler's syndrome (SchS) is an autoinflammatory disease characterized by a chronic urticarial rash, a monoclonal component and signs of systemic inflammation. Interleukin ( IL)-1β is pivotal in the pathophysiology. Objectives Here we investigated the cellular source of proinflammatory mediators in the skin of patients with SchS. Methods Skin biopsies of lesional and nonlesional skin from eight patients with SchS and healthy controls, and patients with cryopyrin-associated periodic syndrome ( CAPS), delayed-pressure urticaria ( DPU) and cold-contact urticaria ( CCU) were studied. We studied in vivo IL-1β, IL-17 and antimicrobial protein ( AMP) expression in resident skin cells and infiltrating cells. In addition we investigated the in vitro effect of IL-1β, IL-17 and polyinosinic-polycytidylic acid (poly: IC) stimulation on cultured epidermal keratinocytes. Results Remarkably, we found IL-1β-positive dermal mast cells in both lesional and nonlesional skin of patients with SchS, but not in healthy control skin and CCU, and fewer in CAPS. IL-17-positive neutrophils were observed only in lesional SchS and DPU skin. In lesional SchS epidermis, mRNA and protein expression levels of AMPs were strongly increased compared with nonlesional skin and that of healthy controls. When exposed to IL-1β, poly: IC or IL-17, patient and control primary human keratinocytes produced AMPs in similar amounts. Conclusions Dermal mast cells of patients with SchS produce IL-1β. This presumably leads to activation of keratinocytes and neutrophil influx, and further amplification of inflammation by IL-17 (from neutrophils and mast cells) and epidermal AMP production leading to chronic histamine-independent neutrophilic urticarial dermatosis. [ABSTRACT FROM AUTHOR]

People living with chronic illness often report uncertainty about the future, fear of disease progression, fear of becoming physically disabled, and a reduced life expectancy as important sources of stress. However, little is known about psychological interventions targeting these concerns. The aim of this study is to illustrate an intervention to reduce emotional distress and concerns about the future in a patient with systemic sclerosis (SSc), a rare chronic rheumatic disease with serious consequences for most patients, and to present a preliminary report on its effectiveness using a single-case study design. Because of the complexity of symptoms and complaints due to SSc, the psychological intervention was embedded in an interdisciplinary care program also consisting of physical therapy, occupational therapy, and specialized nurse care. [ABSTRACT FROM AUTHOR]

Simple Summary: A critical step in the success of immunotherapy is the presentation of tumor-derived peptides by the major histocompatibility complex I (MHC-I) of tumor cells. These neoantigens are potentially immunogenic and trigger immune responses orchestrated by cytotoxic cells. In malignant mesothelioma (MM), tumor development is nevertheless characterized by a low mutation rate despite major structural chromosomal rearrangements driving oncogenesis. In this paper, we propose a paradigm based on the mechanisms of the DNA damage tolerance (DDT) pathways to increase the frequency of non-synonymous mutations. The idea is to transiently activate the error-prone DDT in order to generate neoantigens while preserving a fully competent antitumor immune response. Immunotherapy based on two checkpoint inhibitors (ICI), programmed cell death 1 (PD-1, Nivolumab) and cytotoxic T-lymphocyte 4 (CTLA-4, Ipilimumab), has provided a significant improvement in overall survival for malignant mesothelioma (MM). Despite this major breakthrough, the median overall survival of patients treated with the two ICIs only reached 18.1 months vs. 14 months in standard chemotherapy. With an objective response rate of 40%, only a subset of patients benefits from immunotherapy. A critical step in the success of immunotherapy is the presentation of tumor-derived peptides by the major histocompatibility complex I (MHC-I) of tumor cells. These neoantigens are potentially immunogenic and trigger immune responses orchestrated by cytotoxic cells. In MM, tumor development is nevertheless characterized by a low mutation rate despite major structural chromosomal rearrangements driving oncogenesis (BAP1, NF2, CDKN2AB). In this opinion, we propose to investigate an approach based on the mechanisms of the DNA damage tolerance (DDT) pathways to increase the frequency of non-synonymous mutations. The idea is to transiently activate the error-prone DDT in order to generate neoantigens while preserving a fully competent antitumor immune response. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapies for squamous cell carcinomas of the head and neck (SCCHN) have been rapidly evolving, initially with the inclusion of immunotherapy, but more recently with the consideration of anti-angiogenic therapies. Recent preclinical and clinical data reveal a strong correlation between vascular endothelial growth factor (VEGF) and the progression of SCCHN, with nearly 90% of these malignancies expressing VEGF. Our review article not only elaborates on the utility of anti-VEGF therapies on SCCHN but also its interaction with the immune environment. Furthermore, we detailed the current data on immunotherapies targeting SCCHN and how this could be coupled with anti-angiogenics therapies. Despite the lack of approved anti-angiogenic therapies in squamous cell carcinoma of the head and neck (SCCHN), preclinical and more recent clinical evidence support the role of targeting the vascular endothelial growth factor (VEGF) in this disease. Targeting VEGF has gained even greater interest following the recent evidence supporting the role of immunotherapy in the management of advanced SCCHN. Preclinical evidence strongly suggests that VEGF plays a role in promoting the growth and progression of SCCHN, and clinical evidence exists as to the value of combining this strategy with immunotherapeutic agents. Close to 90% of SCCHNs express VEGF, which has been correlated with a worse clinical prognosis and an increased resistance to chemotherapeutic agents. As immunotherapy is currently at the forefront of the management of advanced SCCHN, revisiting the rationale for targeting angiogenesis in this disease has become an even more attractive proposition. [ABSTRACT FROM AUTHOR]

Background: A program supporting the initiation of insulin therapy in primary care was introduced in Belgium, as part of a larger quality improvement project on diabetes care. This paper reports on a study exploring factors influencing the engagement of general practitioners (GPs) in insulin therapy initiation (research question 1) and exploring factors relevant for future program development (research question 2). Methods: We have used semi-structured interviews to answer the first research question: two focus group interviews with GPs who had at least one patient in the insulin initiation program and 20 one-to-one interviews with GPs who were not regular users of the overall support program in the region. To explore factors relevant for future program development, the data from the GPs were triangulated with data obtained from individual interviews with patients (n = 10), the diabetes nurse educator (DNE) and the specialist involved in the program, and data extracted from meeting reports evaluating the insulin initiation support program. Results: We found differences between GPs engaged and those not engaged in insulin initiation in attitude, subjective norm and perceived behavioural control regarding insulin initiation. In general the support program was evaluated in a positive way by users of the program. Some aspects need further consideration: job boundaries between the DNE and GPs, job boundaries between GPs and specialists, protocol adherence and limited case load. Conclusion: The study shows that the transition of insulin initiation from secondary care to the primary care setting is a challenge. Although a support program addressing known barriers to insulin initiation was provided, a substantial number of GPs were reluctant to engage in this aspect of care. Important issues for future program development are: an interdisciplinary approach to job clarification, a dynamic approach to the integration of expertise in primary care and feedback on protocol adherence. Trial registration: ClinicalTrials.gov Identifier: NCT00824499 [ABSTRACT FROM AUTHOR]

Although studies have addressed the exhaustion of the host's immune response to HCV and its role in treatment, there is little information about the possible contribution of innate immunity to treatment-induced clearance. We hypothesized that because intact myeloid dendritic cell (MDC) pathogen sensing functions are associated with improved HCV-specific CD8+ T cell functionality in some chronically infected patients, it might enhance HCV clearance rate under standard interferon therapy. To investigate this hypothesis, TLR-induced MDC activation and HCV-specific CD8+ T cell response quality were monitored longitudinally at the single-cell level using polychromatic flow cytometry in chronically infected patients undergoing interferon therapy. We correlated the immunological, biochemical and virological data with response to treatment. We demonstrate that the clinical efficacy of interferon-induced viral clearance is influenced by the extent to which HCV inhibits MDC functions before treatment, rather than solely on a breakdown of the extrinsic T cell immunosuppressive environment. Thus, viral inhibition of MDC functions before treatment emerges as a co-determining factor in the clinical efficacy of interferon therapy during chronic HCV infection. [ABSTRACT FROM AUTHOR]

The article presents three case studies involving patients with acute lymphoblastic leukemia (ALL) who developed L-asparaginase (L-ase)-induced severe acute hepatotoxicity with liver steatosis including a 60-year-old women, a 51-year-old man, and a 64-year-old woman. The article discusses the adverse effect of treatment with L-ase, treatment with the mitochondrial cofactors vitamin B complex and L-carnitine, and the effectiveness of the patients' treatment regimens.

Treatment of "subacromial impingement syndrome" of the shoulder has changed drastically in the past decade. The anatomical explanation as "impingement" of the rotator cuff is not sufficient to cover the pathology. "Subacromial pain syndrome", SAPS, describes the condition better. A working group formed from a number of Dutch specialist societies, joined by the Dutch Orthopedic Association, has produced a guideline based on the available scientific evidence. This resulted in a new outlook for the treatment of subacromial pain syndrome. The important conclusions and advice from this work are as follows: (1) The diagnosis SAPS can only be made using a combination of clinical tests. (2) SAPS should preferably be treated non-oper-atively. (3) Acute pain should be treated with analgetics if necessary. (4) Subacromial injection with corticosteroids is indicated for persistent or recurrent symptoms. (5) Diagnostic imaging is useful after 6 weeks of symptoms. Ultrasound examination is the recommended imaging, to exclude a rotator cuff rupture. (6) Occupational interventions are useful when complaints persist for longer than 6 weeks. (7) Exercise therapy should be specific and should be of low intensity and high frequency, combining eccentric training, attention to relaxation and posture, and treatment of myofascial trigger points (including stretching of the muscles) may be considered. (8) Strict immobilization and mobilization techniques are not recommended. (9) Tendinosis calcarea can be treated by shockwave (ESWT) or needling under ultrasound guidance (barbotage). (10) Rehabilitation in a specialized unit can be considered in chronic, treatment resistant SAPS, with pain perpetuating behavior. (11) There is no convincing evidence that surgical treatment for SAPS is more effective than conservature management. (12) There is no indication for the surgical treatment of asymptomatic rotator cuff tears. [ABSTRACT FROM AUTHOR]

Background. Despite stable overall antibiotic use between 2007 and 2011 in The Netherlands, use of nitrofurantoin and trimethoprim increased by 32%. The background of this increased antibiotic use against uropathogens is unknown. Objectives. To determine whether increased use of urinary tract infection antibiotics is caused by changes in patients’ consultation or physicians’ prescribing behaviour and to investigate attitudes and opinions of women with respect to cystitis management and antibiotics. Methods. Consultation and prescribing for International Classification of Primary Care (ICPC) codes U01 (dysuria), U02 (frequency), U05 (other urination problems), U70 (pyelonephritis) and U71 (cystitis) were determined from 2007 to 2010, using routinely collected primary health care data. Separately, behaviour of women with respect to managing cystitis, consultation and opinions towards (delayed) antibiotic treatment were studied using questionnaires in 2012. Results. Consultation for U02 and U71 significantly increased from 93 to 114/1000 patient-years from 2007 to 2010; proportion of episodes in which an antibiotic was prescribed remained constant. Questionnaires revealed that urination problems and pain were dominant complaints of cystitis; pain medication, however, was not adequately used. One-third of women directly consult upon first symptoms, whereas the majority awaits an average of 4 days. Sixty-six per cent of women report to be willing to postpone antibiotic use. Conclusion. Increased use of urinary tract infection antibiotics may be caused by increased consultation for cystitis in primary care. Future research should focus on the outcomes of adequate pain medication, enhanced diagnostic procedures and of delaying antibiotic use in cystitis management. [ABSTRACT FROM PUBLISHER]

Background: Recently, we have shown that intraplaque mast cell numbers are associated with atherosclerotic plaque vulnerability and with future cardiovascular events, which renders inhibition of mast cell activation of interest for future therapeutic interventions. However, the endogenous triggers that activate mast cells during the progression and destabilization of atherosclerotic lesions remain unidentified. Mast cells can be activated by immunoglobulins and in the present study, we aimed to establish whether specific immunoglobulins in plasma of patients scheduled for carotid endarterectomy were related to (activated) intraplaque mast cell numbers and plasma tryptase levels. In addition, the levels were related to other vulnerable plaque characteristics and baseline clinical data. Methods and Results: OxLDL-IgG, total IgG and total IgE levels were measured in 135 patients who underwent carotid endarterectomy. No associations were observed between the tested plasma immunoglobulin levels and total mast cell numbers in atherosclerotic plaques. Furthermore, no associations were found between IgG levels and the following plaque characteristics: lipid core size, degree of calcification, number of macrophages or smooth muscle cells, amount of collagen and number of microvessels. Interestingly, statin use was negatively associated with plasma IgE and oxLDL-IgG levels. Conclusions: In patients suffering from carotid artery disease, total IgE, total IgG and oxLDL-IgG levels do not associate with plaque mast cell numbers or other vulnerable plaque histopathological characteristics. This study thus does not provide evidence that the immunoglobulins tested in our cohort play a role in intraplaque mast cell activation or grade of atherosclerosis. [ABSTRACT FROM AUTHOR]

Purpose: Many systematic reviews have been published on surgical interventions for low back disorders. The objective of this overview was to evaluate the available evidence from systematic reviews on the effectiveness of surgical interventions for disc herniation, spondylolisthesis, stenosis, and degenerative disc disease (DDD). An earlier version of this review was published in 2006 and since then, many new, better quality reviews have been published. Methods: A comprehensive search was performed in the Cochrane database of systematic reviews (CDSR), database of reviews of effectiveness (DARE) and Pubmed. Two reviewers independently performed the selection of studies, risk of bias assessment, and data extraction. Included are Cochrane reviews and non-Cochrane systematic reviews published in peer-reviewed journals. The following conditions were included: disc herniation, spondylolisthesis, and DDD with or without spinal stenosis. The following comparisons were evaluated: (1) surgery vs. conservative care, and (2) different surgical techniques compared to one another. The methodological quality of the systematic reviews was evaluated using AMSTAR. We report (pooled) analyses from the individual reviews. Results: Thirteen systematic reviews on surgical interventions for low back disorders were included for disc herniation ( n = 6), spondylolisthesis ( n = 2), spinal stenosis ( n = 4), and DDD ( n = 4). Nine (69 %) were of high quality. Five reviews provided a meta-analysis of which two showed a significant difference. For the treatment of spinal stenosis, intervertebral process devices showed more favorable results compared to conservative treatment on the Zurich Claudication Questionnaire [mean difference (MD) 23.2 95 % CI 18.5-27.8]. For degenerative spondylolisthesis, fusion showed more favorable results compared to decompression for a mixed aggregation of clinical outcome measures (RR 1.40 95 % CI 1.04-1.89) and fusion rate favored instrumented fusion over non-instrumented fusion (RR 1.37 95 % CI 1.07-1.75). Conclusions: For most of the comparisons, the included reviews were not significant and/or clinically relevant differences between interventions were identified. Although the quality of the reviews was quite acceptable, the quality of the included studies was poor. Future studies are likely to influence our assessment of these interventions. [ABSTRACT FROM AUTHOR]

Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E. faecium and E. faecalis. These new antibacterial agents include teixobactin (targeting lipid II and lipid III), lipopeptides derived from nisin (targeting lipid II), dimeric vancomycin analogues (targeting lipid II), sortase transpeptidase inhibitors (targeting the sortase enzyme), alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors (targeting LtaS), various oxazolidinones (targeting the bacterial ribosome), and tarocins (interfering with teichoic acid biosynthesis). The targets of these novel compounds and mode of action make them very promising for further antimicrobial drug development and future treatment of Gram-positive bacterial infections. Here we review current knowledge of the most favorable anti-enterococcal compounds along with their implicated modes of action and efficacy in animal models to project their possible future use in the clinical setting. [ABSTRACT FROM AUTHOR]

Background and objective One of the treatment options for arteriovenous malformations consists of embolization, with a choice of various embolic agents, with or without subsequent surgical excision. If embolization is offered without subsequent surgery, the embolic material will stay in situ, in which case the consistency and color become important in superficial lesions. The purpose of this case report is to describe if the use of a novel liquid embolic agent (PHIL) is well suited for treatment of superficial AVMs without subsequent surgery. Case description A 30-year-old male presented with a painful reddish, pulsatile swelling of the left ear that had been present for more than 10 years. Angiography confirmed an arteriovenous malformation supplied by the superficial temporal artery and the posterior auricular artery. The lesion was successfully treated by embolization with PHIL, through the superficial temporal artery. A minute residual shunt, from the posterior auricular artery, was accepted. Immediate disappearance of pulsatile tinnitus was reported. Moreover, return of normal skin color was observed without discomfort from the embolic deposits. This result has been stable throughout one year of clinical follow-up. Conclusion To our knowledge, this is the first case report describing PHIL embolization as a treatment option for superficial arteriovenous malformations without the necessity for subsequent surgery. The white color and rubbery consistency are beneficial characteristics of PHIL in treatment of subcutaneous lesions, especially in cosmetically relevant locations. [ABSTRACT FROM AUTHOR]