Abstract
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In a laboratory experiment (repeated eight times) individuals of six small rodent species were mixed with 500 Ixodes ricinus larvae for 24 h, than over a 3-day-long observation period engorged ticks fallen from individually kept rodents were counted. Forty engorged larvae fell from the hosts, 25% from striped field mice, 32.5% from house mice, 22.5% from common voles, 10% from bank voles, while wood mouse and steppe mouse proved to be almost free of successfully infesting ticks (both 5%). Statistical analysis indicated, that tick burden differed significantly among host species. Similarly significant differences were shown between sensitivity of two related species, house mouse and steppe mouse, and more ticks were collected on the second observation day compared to the first day. The difference in susceptibility of hosts to Ixodes infestation could be due to various anti-tick behavior habits of hosts, or difference in preference of the ticks between host species.
Ventilation through an extraglottic tracheal tube: a technique for deep extubation and airway control |
Wed, 07 Jun 2017 05:57:03 +0000 |
,The parable of Buridan's ass |
Wed, 07 Jun 2017 05:46:05 +0000 |
„Ich möchte Neuheiten begutachten — den State-of-the-art der Zahnheilkunde inklusive aller aktuellen Innovationen auf einen Blick. Dazu interessante Leute treffen, auch Bekannte wiedersehen, Gespräche führen und meinen Horizont erweitern", so lauteten die generellen Erwartungen angehender junger Zahnärzte an die Internationale Dental-Schau (IDS). Das klingt ganz ähnlich wie bei vielen „alten Hasen", die schon zum zehnten oder zwanzigsten Mal dabei waren. Und doch erlebten Zahnmedizinstudenten, Berufseinsteiger und Kollegen in den ersten Jahren nach ihrer Niederlassung die IDS 2017 etwas anders ...
Die Veranstaltung der DG PARO — Young-Professionals jährt sich zum fünften Mal. Veranstaltungsort am 8. Juli 2017 wird das Hyatt Regency Hotel im Düsseldorfer Medienhafen sein, das einen tollen Ausblick auf Hafen, Altstadt, Rheinturm und Skyline bietet und somit einen idealen Rahmen für den fachlichen Diskurs darstellt.
The origin, differentiation and functional ultrastructure of oncospheral or egg envelopes in Echinococcus multilocularis Leuckart, 1863 were studied by transmission electron microscopy (TEM) and cytochemistry. The purpose of our study is to describe the formation of the four primary embryonic envelopes, namely vitelline capsule, outer envelope, inner envelope and oncospheral membrane, and their transformation into the oncospheral or egg envelopes surrounding the mature hexacanth. This transformation takes place in the preoncospheral phase of embryonic development. The vitelline capsule and oncospheral membrane are thin membranes, while the outer and inner envelopes are thick cytoplasmic layers formed by two specific types of blastomeres: the outer envelope by cytoplasmic fusion of two macromeres and the inner envelope by cytoplasmic fusion of three mesomeres. Both outer and inner envelopes are therefore cellular in origin and syncytial in nature. During the advanced phase of embryonic development, the outer and inner envelopes undergo great modifications. The outer envelope remains as a metabolically active layer involved in the storage of glycogen and lipids for the final stages of egg development and survival. The inner envelope is the most important protective layer because of its thick layer of embryophoric blocks that assures oncospheral protection and survival. This embryophore is the principal layer of mature eggs, affording physical and physiological protection for the differentiated embryo or oncosphere, since the outer envelope is stripped from the egg before it is liberated. The embryophore is very thick and impermeable, consisting of polygonal blocks of an inert keratin-like protein held together by a cementing substance. The embryophore therefore assures extreme resistance of eggs, enabling them to withstand a wide range of environmental temperatures and physicochemical conditions.
In this work, we develop a device, called 'Walk-Even', that can provide real-time feedback to correct gait asymmetry commonly exhibited in post-stroke survivors and persons with certain neurological disorders. The device computes gait parameters, including gait time, swing time, and stance time of each leg, to detect gait asymmetry and provide corresponding real-time biofeedback by means of auditory and electrotactile stimulation to actively correct the user's gait. The system consists of customized force-sensor-embedded insoles adjustable to fit any shoe size, electrotactile and auditory feedback circuits, microcontroller, and wireless XBee transceivers. The device also offers data saving capability. To validate its accuracy and reliability, we compared the gait measurements from our device with a commercial gait and balance assessment device, Zeno Walkway. The results show good correlation and agreement in a validity study with six healthy subjects and reliability study with seventeen healthy subjects. In addition, preliminary testing on six post-stroke patients after an 8-week training shows that the Walk-Even device helps to improve gait symmetry, foot pressure and forefoot loading of the affected side. Thus, initial testing indicates that the device is accurate in measuring the gait parameters and effective in improving gait symmetry using real-time feedback. The device is portable and low cost and has the potential for use in a non-clinical setting for patients that can walk independently without assistance. A more extensive testing with stroke patients is still ongoing.
Abdominalperineal resection (APR) represents the gold standard for lower third of rectum and anal cancer; after this wide excision, it results a large non-collapsible dead space that tends to collect fluid, increasing the risk of infection and wound dehiscence. Moreover, APR is associated to neoadjuvant/adjuvant radiation therapy with further risk of local complications. In this background, flap reconstruction after APR o eAPR represents the best strategy for minimizing tension in skin closure, providing healthy well vascularized and restoring a good functional local anatomy.
A retrospective study was performed at the Department of Plastic Reconstructive and Aesthetic Surgery at the University Hospital Città della Salute e della Scienza of Turin from March 2013 to November 2016: 11 patients were included in the study: 5 men and 6 women aged 53 to 76 years (mean ± SD age: 66 ± 7 years). All of them received eAPR (extended-APR). Seven patients required a total dose of 20Gy as neoadjuvant radiotherapy treatment and 6 patients needed adjunctive chemotherapy treatment. Skin defects size ranged from 56 to 180 cm2 (mean 114 ± 38 cm2). Skin defect less than 5 cm of maximum width was not included in the study because no major reconstructions were needed. Surgical reconstruction was planned depending on sacrectomy eventually associated to eAPR and defect size too. Planned follow-up was carried out at 1, 3, and 6 months recording clinical data, local and systemic complications, and pain evaluation at sitting position and during normal walking activity.
Wound healing was achieved in all patients within a period of 21 days. Only one patient showed partial flap necrosis and required wound surgical revision with simple skin closure. Another one patient suffered from mild venous congestion and partial flap necrosis was observed: a period of 2 weeks of negative pressure wound therapy and dressing led to complete healing of the defect (both these patients received 20Gy neoadjuvant radiotherapy). Esthetic pleasant results, high patient satisfaction, and no significant motor impairment were recorded among all patients, excepting for just one patient who reports mild walking impairment and pain at sitting position, after the 6th month follow-up. None of the patient referred significant life quality impairment and all of them expressed general high satisfaction concerning reconstructive expectations.
Many flaps can be harvested to fill and close the large defect after eAPR, with respectively advantages and disadvantages, but we found the use composite gluteal flap technique suitable for most of the patients undergoing eAPR, with good functional results and low rates of morbidity and complications.
Level of Evidence: Level IV, therapeutic study.
As of February 2017, approximately 7639 amphibian species have been described in the AmphibiaWeb database. However, only 20 cathelicidin-like antimicrobial peptides have been identified to date from 10 amphibian species. Half of these peptides were identified from genome sequences and have not yet been functionally characterized. In this study, a novel cathelicidin-like peptide designated cathelicidin-PP was purified from the skin of tree frog Polypedates puerensis. Cathelicidin-PP is a 32 residue peptide of sequence ASENGKCNLLCLVKKKLRAVGNVIKTVVGKIA. Circular dichroism spectroscopy indicated that cathelicidin-PP mainly adopts a β-sheet structure in membrane-mimetic solutions. Cathelicidin-PP exhibits potent antimicrobial activity against bacteria and fungi, especially Gram-negative bacteria. Meanwhile, it shows low cytotoxicity toward mammalian cells. Scanning electron microscopy analysis indicated that cathelicidin-PP kills bacteria through the disruption of the bacterial cell membrane integrity. Furthermore, cathelicidin-PP exerts significant anti-inflammatory functions by inhibiting the lipopolysaccharide (LPS)-mediated generation of nitric oxide and pro-inflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6. The MAPKs (ERK, JNK, and p38) and NF-κB signaling pathways are involved in the anti-inflammatory effect. Cathelicidin-PP caused partial neutralization of LPS in a dose-dependent manner. Quantitative PCR indicated that infection of tree frogs with bacteria causes increased expression of cathelicidin-PP in immune-related tissues. Taken together, cathelicidin-PP is the first identified cathelicidin-like peptide from tree frogs. Our findings demonstrate that in addition to direct bactericidal capacity, cathelicidin-PP also possesses immunomodulatory properties, including partial neutralization of LPS, and inhibiting the production of inflammatory cytokines.
Surgical removal plays an important role in treating children's craniopharyngioma. For a safe and minimally invasive craniotomy, a reformed surgical modality was proposed in this paper by combining the insertion of an Ommaya reservoir system (ORS) by stereotactic puncture, aspiration of cystic fluid in 2-day interval for consecutive 7–10 days, and the delayed tumor resection.
Eleven patients (aged from 5 to 9 years old) with giant cystic craniopharyngiomas who had undergone the reformed surgical modality during November 2014 and December 2015 were collected as group A. In contrast, seven patients (aged from 5 to 11 years old) who had undergone the traditional directed operation without any prior management from January 2014 to October 2014 were collected into group B. A retrospective analysis was performed for both groups at one institution. The preoperative and postoperative clinical presentations, neuroimaging, early postoperative outcome, and the surgery-related complications of both groups were reviewed.
For group A, the mean value of the maximum tumor diameters shank from 52.36 to 23.82 mm after implementing aspiration of the cystic fluid in 1-day interval for consecutive 8.23 days. Eight patients (72.73%) in group A underwent a gross total resection (GTR), while two (28.57%) patients underwent GTR in group B. The postoperative electrolyte disturbance rate and endocrine disorder rate of group B were significantly higher than those of group A (42.86 vs 36.36%; 71.43 vs 45.45%). Postoperative long-term diabetes insipidus only occurred in one patient of group B, and postoperative visual deterioration occurred in two patients of group B. Besides, one patient of group B died of severe postoperative hypothalamus dysfunction. Patients with residual tumors were applied with additional adjuvant radiotherapy, and no recurrence was observed in follow-up examinations.
A favorable outcome can be achieved by combining the insertion of an ORS by stereotactic puncture, aspiration of cystic fluid in 2-day interval for continuously 7–10 days, and the delayed tumor resection. This combined treatment modality maybe an effective method to treat children with giant cystic craniopharyngiomas.
Accurate and timely prenatal diagnosis of spina bifida (SB) is a major goal of modern antenatal care. Prenatal screening for open SB should be first performed at the time of routine first-trimester ultrasound by examining the posterior fossa for obliteration or non-visualization of the fourth ventricle ("intracranial translucency") and cisterna magna. The second step of screening is the second-trimester anatomy scan, at which time the features of the Chiari type II malformation should be looked for, including ventriculomegaly, scalloping of the frontal bones ("lemon" sign), and backward and caudal displacement of the cerebellar vermis with obliteration of the cisterna magna ("banana" sign). In cases with positive findings, evaluation must include a focused examination of the spine for defects. In cases of closed SB and SB occulta, the cranial and posterior fossa features will not be present as they are not associated with leaking of spinal fluid and resultant hindbrain herniation, highlighting the fact that the spine should be examined thoroughly whenever possible during the second-trimester scan. In tertiary fetal medicine centers, two-dimensional and three-dimensional ultrasound allows an accurate determination of the location, type, extent, and upper level of the spinal defect as well as the presence of associated anomalies. Fetal magnetic resonance imaging should be restricted to candidates for intrauterine surgery as part of the preoperative protocol.
The precise incidence of hydrocephalus in patients with mucopolysaccharidoses (MPS) is hard to determine, because the condition lacks a formal, consensus-based definition. The diagnosis of hydrocephalus depends on symptom profile, presence of neuroimaging features, and the outcome of diagnostic tests. Although numerous techniques are used to identify MPS patients who are most likely to have hydrocephalus and respond to treatment, no definitive method exists to prove diagnosis.
The authors propose an algorithm to aid in the diagnosis and management of hydrocephalus in MPS patients.
The theory of venous hypertension associated with the morphological changes in the skull base and craniocervical junction indicate the need for future neuroimaging studies including cerebrospinal fluid (CSF) and venous flow measurements to monitor hydrocephalus progression and select therapeutic interventions in MPS patients. Preoperative planning should also be based on the increased risk of intraoperative and postoperative hemorrhagic complications.
The specific antibody response to the unconjugated 23-valent pneumococcal polysaccharide vaccine is one of the most common tests used to assess for possible humoral immunodeficiency. The results can be difficult to interpret because most people have been immunized with one or more of the pneumococcal vaccines and there is controversy regarding what constitutes a normal response. To circumvent this problem, we developed an ELISA to measure IgG-specific antibodies to the Salmonella Vi Typhim (S. Typhim) vaccine, a pure polysaccharide vaccine, which is a neoantigen for the vast majority of people in the USA.
We compared the pre- and post-vaccination serum titers to the Vi Typhim vaccine in healthy controls (n = 22), patients previously diagnosed with a primary immunodeficiency (n = 30), and patients referred for possible humoral immune deficiency (n = 29). We also determined if the S. Typhim vaccine could be used to assess specific antibody responses in people on antibody replacement therapy.
Following immunization with the S. Typhim vaccine, we found that a 2-fold increase in titers is 100% sensitive and specific in detecting known humoral immune deficiencies as determined by ROC curve analysis. This cut-off value was successfully applied to possible immune deficiency patients (n = 29), resulting in the diagnosis of seven subjects with humoral immunodeficiency. The use of immunoglobulin replacement therapy did not affect the median response ratios compared to subjects not receiving gammaglobulin.
This study suggests that measurement of the specific antibody response to the S. Typhim vaccine may have advantages over pneumococcal vaccination in the evaluation of the humoral immune response.
Single nucleotide polymorphisms (SNPs), genetic background, and epigenetics play important roles in rheumatoid arthritis (RA). These factors can be useful in RA diagnosis, prognosis, and treatment response evaluation, particularly with the growing trends in personalized medicine. Therefore, categorizing classic genes and SNPs in RA can present an appropriate guideline for RA management.
Prognostic and diagnostic biomarkers play important roles in RA diagnosis and treatment. Categorizing SNPs is not an easy process yet, but selecting classic SNPs can be useful worldwide, according to basic similarities that exist in genomes. In this review, we compiled some of these RA-associated SNPs and biomarkers in a table, according to newly identified factors. The role of epigenetics in RA is undeniable; using epigenetic biomarkers like histone deacetylase (HDACs) can be useful in RA diagnosis and treatment. miRs such as miR-146a, miR-155, and miR-222 are useful in diagnosis and can be used in treatment by interfering with other factors' functions. Interleukins (ILs) seem to be good prognostic and diagnostic markers and can be targeted in RA treatment.
Using multiple types of biomarkers, such as genes, SNPs, and epigenetic biomarkers like HDACs can be useful in RA management and treatment. PTPN22, HLA-DR polymorphisms, miRs, and HDACs are considerable in RA susceptibility; hence, they can be valuable biomarkers in future studies. This article gathered separate information from approximately 100 articles to present useful biomarkers and polymorphisms in one review.
To assess the diagnostic confidence in detecting and localizing areas of bone marrow edema in the sacroiliac joint of patients with suspected spondyloarthritis using a single-plane method and comparing it with multiplanar unenhanced and enhanced methods.
Patients with clinical suspicion of spondyloarthritis undergoing an MRI of the sacroiliac joint were included in this retrospective study. To assess sacroiliitis, three methods were applied: single-plane (i.e., para-coronal STIR alone), multiplanar unenhanced (i.e., para-coronal STIR and para-axial PD-fs), and multiplanar enhanced method (i.e., para-coronal and para-axial post-contrast T1-fs). Two 4-point scales were used to evaluate, respectively, the diagnostic confidence in detection and localization of bone marrow edema. The distribution of certain and uncertain rating according to signal intensity and size of the lesions was also calculated.
Seventy-four patients met the inclusion criteria. Both multiplanar methods increased the diagnostic confidence in detection (p < 0.001) and localization (p < 0.001) of sacroiliitis; no significant difference occurred between the multiplanar unenhanced and enhanced methods (p = 0.405 and p = 1.00, respectively, for detection and localization). A statistically significant difference between the distributions of certain and uncertain rating for detection based on the size and signal intensity of each lesion emerged (p = 0.006 and p < 0.001, respectively), whereas no statistically significant difference occurred for the confidence of localization (p = 0.452 and p = 0.694, respectively).
The multiplanar methods increased the diagnostic confidence in detection and localization of sacroiliitis. The absence of a significant difference between the proposed unenhanced and enhanced methods suggests that contrast medium is not mandatory for the detection of sacroiliitis.
Computational prediction of intrinsic disorder in protein sequences dates back to late 1970 and has flourished in the last two decades. We provide a brief historical overview, and we review over 30 recent predictors of disorder. We are the first to also cover predictors of molecular functions of disorder, including 13 methods that focus on disordered linkers and disordered protein–protein, protein–RNA, and protein–DNA binding regions. We overview their predictive models, usability, and predictive performance. We highlight newest methods and predictors that offer strong predictive performance measured based on recent comparative assessments. We conclude that the modern predictors are relatively accurate, enjoy widespread use, and many of them are fast. Their predictions are conveniently accessible to the end users, via web servers and databases that store pre-computed predictions for millions of proteins. However, research into methods that predict many not yet addressed functions of intrinsic disorder remains an outstanding challenge.
The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration. Diabetic rats were injected intraperitoneally with 0.03 μg exendin-4/kg body weight/daily or treated with 5 ppm selenium in drinking water for a period of 4 weeks. GLP-1R and IRS-1 levels were decreased while the level of preproinsulin messenger RNA (mRNA) was increased in the pancreas of diabetic untreated rats, as compared to that in control rats. Treatment of diabetic rats with exendin-4 increased protein and mRNA levels of GLP-1R, and IRS-1, and the mRNA level of preproinsulin in the pancreas, as compared to their levels in diabetic untreated rats. Selenium treatment of diabetic rats increased the pancreatic mRNA levels of GLP-1R, IRS-1, and preproinsulin. Exendin-4 or selenium treatment of diabetic rats also increased the numbers of pancreatic islets and GLP-1R molecules in the pancreas. Therefore, exendin-4 and selenium may exert their antidiabetic effects by increasing GLP-1R, IRS-1, and preproinsulin expression in the pancreas and by increasing the number of pancreatic islets.
Recently, it is common to perform the Fontan procedure after the Glenn procedure as surgical repair for the univentricular heart. How the brain oxygen saturation (rSO2) values change with the cardiac restoration and the process of growth during these procedures in individual children remains unknown. In this study, we retrospectively studied rSO2 data as well as the perioperative clinical records of 30 children who underwent both Glenn and Fontan procedures by the same surgeon in the same institute. The rSO2 was measured at the beginning and end of each procedure with an INVOS 5100C. Cerebral perfusion pressure was calculated by subtracting central venous pressure from mean arterial pressure. Arterial oxygen saturation (SaO2) and the hemoglobin concentration were obtained as candidates affecting rSO2 changes at the start and the end of both procedures. The rSO2 increased during the Glenn procedure, but this increase was slight and insignificant. On the other hand, the rSO2 significantly increased during the Fontan procedure. Significant increases in SaO2 were observed only between the beginning and end of the Fontan procedure. Correlation coefficients determined by linear regression analysis were more than 0.5 between rSO2 and SaO2 in both procedures. Multiple linear regression analysis showed that SaO2 was the key determinant of the rSO2. The rSO2 increases step by step from the Glenn to the Fontan procedure in the same patient. Within each procedure, SaO2 is the key determinant of the rSO2. The significance of rSO2 monitoring in these procedures should be further evaluated.
A 20-month-old boy with Williams syndrome had undergone multiple surgical and catheter-based interventions for resistant peripheral pulmonary arterial stenoses with eventual bilateral stent placement and conventional balloon angioplasty. He persistently developed suprasystemic right ventricular (RV) pressure. Angioplasty with a drug-coated balloon (DCB) was performed for in-stent restenosis and to remodel his distal pulmonary vessels bilaterally. This resulted in immediate improvement in the in-stent stenosis and resultant decrease in RV pressure. Follow-up catheterization two months later continued to show long-lasting improvement in the in-stent stenosis. We hypothesize that the anti-proliferative effects of DCBs may be of benefit in the arteriopathy associated with Williams syndrome. We report this as a novel use of a DCB in the pulmonary arterial circulation in a patient with Williams syndrome.
Superabsorbent polymer based on Polyaspartic acid (PASP) and 2-acrylamido-propane sulphonic acid (AMPS) has been synthesized to achieve maximum swelling with deionized water. The swelling properties of the polymer have been studied in different physiological fluids viz. saline and glucose. Best swelling has been observed in glucose solution. Studies at different pH have shown that the polymer has better swelling under extreme acidic and alkaline conditions. A parabolic curve has been observed. The polymer based on PASP and AMPS is sensitive to glucose and pH conditions. This property can be exploited for diabetic /chronic wound dressing. The polymer has also been evaluated for their blood compatibility, encapsulation efficiency and release of peptide GHK-Cu having dermatological application. The polymer and the encapsulated polymer structure have been studied using FTIR and SEM with EDAX. An encapsulation efficiency of 72.8% was achieved and a release of 88.46% was observed in 24h.
Chiari malformation type I (CM-I), described by a descent of the cerebellar tonsils, is assumed to be a neurological developmental disorder. The aim of the present study was to investigate morphological variance in cerebellar sub-structures, including gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), using magnetic resonance (MR) images with three-dimensional (3D) fractal dimension (FD) analysis in patients with CM-I. MRI data of 16 patients and 15 control subjects were obtained, and structural complexity analyses were performed using a box-counting FD algorithm. Results showed that patients with CM-I had significantly reduced FD values for WM and CSF in comparison with controls, and statistically significant differences in cerebellar GM and CSF volumes between patients and controls were found. Moreover, a significant difference was not found between the WM volumes. This may suggest that there are changes in structural complexity in WM even when its volume is unaffected. We conclude that the findings of this preliminary study indicate the possibility of using FD analysis to understand the pathophysiology of CM-I in patients.
Positive activity behaviours (i.e. higher physical activity [PA]/lower sedentary behaviour [SB]) are beneficial from infancy, yet evidence suggests that young children (0- to 6-year-olds) are relatively inactive. To better understand the perceived influences on these behaviours and to aid intervention development, this paper systematically synthesizes the extensive qualitative literature regarding perceived barriers and facilitators to PA and SB in young children (0–6 years old). A search of eight electronic databases (July 2016) identified 43 papers for inclusion. Data extraction and evidence synthesis were conducted using thematic content analysis, underpinned by the socio-ecological model (i.e. individual, interpersonal, community, organizational and policy levels). Parents, childcare providers and children perceived seven broad themes to be important for PA and SB, including the child; the home; out-of-home childcare; parent–childcare provider interactions; environmental factors; safety; and weather. Each theme mapped onto between one and five levels of the socio-ecological model; barriers and facilitators at the interpersonal level (e.g. parents, care providers and family) were most frequently cited, reflecting the important (perceived) role adults/peers play in shaping young children's behaviours. We provide an overarching framework to explain PA and SB in early childhood. We also highlight where gaps in the current literature exist (e.g. from male carers; in developing countries; and barriers and facilitators in the environmental and policy domains) and where future quantitative work may focus to provide novel insights about children's activity behaviours (e.g. safety and weather).
The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration. Diabetic rats were injected intraperitoneally with 0.03 μg exendin-4/kg body weight/daily or treated with 5 ppm selenium in drinking water for a period of 4 weeks. GLP-1R and IRS-1 levels were decreased while the level of preproinsulin messenger RNA (mRNA) was increased in the pancreas of diabetic untreated rats, as compared to that in control rats. Treatment of diabetic rats with exendin-4 increased protein and mRNA levels of GLP-1R, and IRS-1, and the mRNA level of preproinsulin in the pancreas, as compared to their levels in diabetic untreated rats. Selenium treatment of diabetic rats increased the pancreatic mRNA levels of GLP-1R, IRS-1, and preproinsulin. Exendin-4 or selenium treatment of diabetic rats also increased the numbers of pancreatic islets and GLP-1R molecules in the pancreas. Therefore, exendin-4 and selenium may exert their antidiabetic effects by increasing GLP-1R, IRS-1, and preproinsulin expression in the pancreas and by increasing the number of pancreatic islets.
The specific antibody response to the unconjugated 23-valent pneumococcal polysaccharide vaccine is one of the most common tests used to assess for possible humoral immunodeficiency. The results can be difficult to interpret because most people have been immunized with one or more of the pneumococcal vaccines and there is controversy regarding what constitutes a normal response. To circumvent this problem, we developed an ELISA to measure IgG-specific antibodies to the Salmonella Vi Typhim (S. Typhim) vaccine, a pure polysaccharide vaccine, which is a neoantigen for the vast majority of people in the USA.
We compared the pre- and post-vaccination serum titers to the Vi Typhim vaccine in healthy controls (n = 22), patients previously diagnosed with a primary immunodeficiency (n = 30), and patients referred for possible humoral immune deficiency (n = 29). We also determined if the S. Typhim vaccine could be used to assess specific antibody responses in people on antibody replacement therapy.
Following immunization with the S. Typhim vaccine, we found that a 2-fold increase in titers is 100% sensitive and specific in detecting known humoral immune deficiencies as determined by ROC curve analysis. This cut-off value was successfully applied to possible immune deficiency patients (n = 29), resulting in the diagnosis of seven subjects with humoral immunodeficiency. The use of immunoglobulin replacement therapy did not affect the median response ratios compared to subjects not receiving gammaglobulin.
This study suggests that measurement of the specific antibody response to the S. Typhim vaccine may have advantages over pneumococcal vaccination in the evaluation of the humoral immune response.
Stathmin (STMN) plays a vital role in maintaining the malignant behavior of cancer through directly regulating microtubule dynamics equilibrium. Taxol, an effective chemotherapeutics mainly acting to promote microtubule polymerization, has been commercially applied in treating solid tumors, which results in serious drug resistance. Our study demonstrated that STMN RNA interference (RNAi) enlarged taxol-induced inhibitions in cellular proliferation, colony formation, and multidimensional spaces of cell immigration and decreased half maximal inhibitory concentration (IC50) of taxol in nonsmall cell lung cancer (NSCLC) NCI-H1299 cells; STMN RNAi and taxol jointly attenuated the expressions of extracellular regulated kinase (ERK), nuclear factor kappa B (NF-κB) and B cell lymphoma-2 (Bcl-2), but up regulated Bax expression and initiated intrinsic cell death pathway by activating caspase-3 and caspase-9, while inhibited interleukin 10 (IL-10) autocrine from cell culture supernatant and xenografted mouse serum, as well as intracellular expressions of IL-10 protein and mRNA in vitro; additionally, neutralizing IL-10 alone would incur cell apoptosis to some degree; the further study confirmed that RNAi targeting STMN promoted the sensitivity of taxol in different NSCLC cells. In vivo animal experiments proved that STMN RNAi and taxol cooperatively inhibited the tumorigenicity of NCI-H1299 cells and histological atypia and Ki-67 proliferative index of xenografted tumors and promoted cell differentiation to a higher grade with well-differentiated indicators of glandular lumen-like structure and proliferative fibroblasts. These findings suggest that silencing STMN alleviates the resistance to taxol and collectively contributes to induce the dysfunction of multiple signals and down regulate the malignancy of tumors; thus, STMN is a promising target in treating refractory tumors.
Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. Real world data on efficacy and safety of TNF-α blockers in the elderly with PsA are lacking. The aim of this study was to evaluate the effectiveness, through the achievement of minimal disease activity (MDA), drug discontinuation rate, and safety in elderly patients with PsA on TNF-α blockers. A multicenter, observational study was carried out in four Italian centers. The assessment of disease activity and safety were performed at the start of anti-TNF-α (T0), at 6 months (T6) and at 12 months (T12). A total of 145 PsA patients were included in the study. At baseline 68 (46.9%) patients were on etanercept, 60 (41.3%) on adalimumab, 11 (7.6%) on golimumab, and 6 (4.1%) on infliximab. All the variables concerning PsA activity showed a statistically significant improvement when comparing T6 and T12 with T0. After 6 and 12 months of therapy, respectively, 31 (22.6%) and 71 (51.8%) patients achieved MDA (p < 0.001). The drug discontinuation rate was 5.5% with a mean of 6.8 months (range 2–10 months), and it was due to lack of efficacy, adverse events, and lost to follow-up. Nine patients (6.2%) reported the onset of mild infections resolved with antimicrobial specific oral regimen without therapy interruption. TNF-α blockers are effective in the achievement of a low disease status and safe in elderly patients with PsA. Therefore, age should not be considered a limitation to their use.
While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients.
Methods and analysisA total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries.
Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes).
Ethics and disseminationEthical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval.
eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts.
Trial registration numberNCT02356081.
Since 2011, the Spanish Society of Family Medicine has recommended general practitioners (GPs) to ask their patients to stop taking antibiotics when they suspect a viral infection. However, this practice is seldom used because uncertainty about diagnosis, and fear of consequences of discontinuing antibiotic therapy, as well as perceived pressure to continue prescribing antibiotics and potential conflict with patients are more of a concern for GPs than antibiotic resistance. The main objective of this study is to determine whether discontinuation of antibiotic therapy when a GP no longer considers it necessary has any impact on the number of days with severe symptoms.
Methods and analysisThis is a multicentre, open-label, randomised controlled clinical trial. The study was conducted in 10 primary care centres in Spain. We included patients from 18 to 75 years of age with uncomplicated acute respiratory tract infections—acute rhinosinusitis, acute sore throat, influenza or acute bronchitis—who had previously taken any dose of antibiotic for <3 days, which physicians no longer considered necessary. The patients were randomly assigned to the usual strategy of continuing antibiotic treatment or to discontinuing antibiotic therapy. A sample size of 240 patients per group was calculated on the basis of a reduction of 1 day in the duration of severe symptoms being a clinically relevant outcome. The primary outcome was the duration of severe symptoms, that is, symptoms scored 5 or 6 by means of validated symptom diaries. Secondary outcomes included antibiotics taken, adverse events, patient satisfaction and complications within the first 3 months.
Ethics and disseminationThe study was approved by the Ethical Board of Fundació Jordi Gol i Gurina (reference number: 16/093). The findings of this trial will bedisseminated through research conferences and peer-reviewed journals.
Trial registration numberNCT02900820; pre-results.
Patterns of infection among children with varying levels of iron status in a malaria endemic area may vary spatially in ways requiring integrated infection and iron deficiency control programmes. The objective of this secondary analysis was to determine the geospatial factors associated with malaria and non-malaria infection status among young Ghanaian children at the end of a 5-month iron intervention trial.
DesignCluster-randomised controlled trial.
SettingRural Ghana
Participants1943 children (6–35 months of age) with geocoded compounds.
InterventionsPoint-of-use fortification with micronutrient powders containing vitamins and minerals with or without iron.
Primary and secondary outcome measuresGeneralised linear geostatistical models with a Matern spatial correlation function were used to analyse four infection response variables, defined using different combinations of inflammation (C-reactive protein, CRP >5 mg/L) and malaria parasitaemia. Analyses were also stratified by treatment group to assess the independent effects of the iron intervention.
ResultsThe by-group and combined-group analyses both showed that baseline infection status was the most consistent predictor of endline infection risk, particularly when infection was defined using parasitaemia. In the No-iron group, age above 24 months and weight-for-length z-score at baseline were associated with high CRP at endline. Higher asset score was associated with a 12% decreased odds of endline infection, defined as CRP >5 mg/L and/or parasitaemia (OR 0.88, 95% credible interval 0.78 to 0.98), regardless of group. Maps of the predicted risk and spatial random effects showed a defined low-risk area around the District centre, regardless of how infection was defined.
ConclusionIn a clinical trial setting of iron fortification, where all children receive treated bed nets and access to malaria treatment, there may be geographical variation in the risk of infection with distinct high-risk and low-risk areas, particularly around municipal centres.
Trial registration numberclinicaltrials.gov, NCT01001871.
To understand attitudes and behaviours of adolescents towards antibiotics, antimicrobial resistance and respiratory tract infections.
DesignQualitative approach informed by the Theory of Planned Behaviour. Semi-structured interviews and focus groups were undertaken. We aimed to inform the development of an intervention in an international setting to improve antibiotic use among adolescents; therefore on completion of thematic analysis, findings were triangulated with qualitative data from similar studies in France, Saudi Arabia and Cyprus to elucidate differences in the behaviour change model and adaptation to diverse contexts.
Setting7 educational establishments from the south of England.
Participants53 adolescents (16–18 years) participated in seven focus groups and 21 participated in interviews.
ResultsMost participants had taken antibiotics and likened them to other common medications such as painkillers; they reported that their peers treat antibiotics like a ‘cure-all’ and that they themselves were not interested in antibiotics as a discussion topic. They demonstrated low knowledge of the difference between viral and bacterial infections.Participants self-cared for colds and flu but believed antibiotics are required to treat other RTIs such as tonsillitis, which they perceived as more ‘serious’. Past history of taking antibiotics for RTIs instilled the belief that antibiotics were required for future RTIs. Those who characterised themselves as ‘non-science students’ were less informed about antibiotics and AMR. Most participants felt that AMR was irrelevant to them and their peers. Some ‘non-science’ students thought resistance was a property of the body, rather than bacteria.
ConclusionAddressing adolescents’ misperceptions about antibiotics and the treatment of RTIs using a behaviour change intervention should help improve antibiotic awareness and may break the cycle of patient demand for antibiotics to treat RTIs amongst this group. Schools should consider educating all students in further education about antibiotic usage and AMR, not only those taking science.
The primary aim of this study is to compare the efficacy of three short-term glucose-lowering interventions (exercise, metformin and dapagliflozin) on glycaemic variability in overweight or obese men and women with elevated diabetes risk (ie, prediabetes, defined as haemoglobin A1c (HbA1c)39–47 mmol/mol / 5.7%–6.4%). The secondary aims are to investigate the effects of the interventions on body composition and cardiometabolic risk factors.
Methods and analysisThe Pre-D Trial is an investigator-initiated, randomised, controlled, parallel, open-label, superiority trial. The study aims to assign 120 participants in a 1:1:1:1 ratio to receive one of four interventions for 13 weeks: (1) dapagliflozin (10 mg once daily); (2) metformin (850 mg twice daily); (3) exercise (interval training, 5 days a week, 30 min per session); or (4) control (lifestyle advice). After the 13 weeks of intervention, a follow-up period of 13 weeks will follow to study the long-term effects of the interventions. The primary endpoint is reduction from baseline to end-of treatment (13 weeks) in mean amplitude of glycaemic excursions measured by continuous glucose monitoring. The secondary endpoints include concomitant changes in various measures of glucose metabolism, body weight, cardiorespiratory fitness, blood pressure, plasma lipids, objectively measured physical activity and dietary intake.
Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the Capital Region and the Danish Medicines Agency. Approval of data and biobank storage has been obtained from the Danish Data Protection Board. The study will be carried out according to the Declaration of Helsinki and to the regulations for good clinical practice. The results from this trial will allow a number of research questions concerning the effect of exercise versus dapagliflozin or metformin in HbA1c-defined prediabetes to be addressed.
Trial registrationNCT02695810
In the UK, it is estimated that a disabling hearing loss (HL) affects 1 in 6 people. HL has functional, economic and social-emotional consequences for affected individuals. Intervention for HL focuses on improving access to the auditory signal using hearing aids or cochlear implants. However, even if sounds are audible and speech is understood, individuals with HL often report increased effort when listening.
Listening effort (LE) may be measured using self-reported measures such as patient-reported outcome measures (PROMs). PROMs are validated questionnaires completed by patients to measure their perceptions of their own functional status and well-being. When selecting a PROM for use in research or clinical practice, it is necessary to appraise the evidence of a PROM’s acceptability to patients, validity, responsiveness and reliability.
Methods and analysisA systematic review of studies evaluating the measurement properties of PROMs available to measure LE in HL will be undertaken. MEDLINE, EMBASE, CINAHL, PsychINFO and Web of Science will be searched electronically. Reference lists of included studies, key journals and the grey literature will be hand-searched to identify further studies for inclusion. Two reviewers will independently complete title, abstract and full-text screening to determine study eligibility. Data on the characteristics of each study and each PROM will be extracted. Methodological quality of the included studies will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, the quality of included PROMs appraised and the credibility of the evidence assessed. A narrative synthesis will summarise extracted data.
Ethics and disseminationEthical permission is not required, as this study uses data from published research. Dissemination will be through publication in peer-reviewed journals, conference presentations and the lead author’s doctoral dissertation. Findings may inform the selection of PROMs used to measure LE in HL.
Dyspnoea consists of multiple dimensions including the intensity, unpleasantness, sensory qualities and emotional responses which may differ between patient groups, settings and in relation to treatment. The Dyspnoea-12 is a validated and convenient instrument for multidimensional measurement in English. We aimed to take forward a Swedish version of the Dyspnoea-12.
MethodsThe linguistic validation of the Dyspnoea-12 was performed (Mapi Language Services, Lyon, France). The standardised procedure involved forward and backward translations by three independent certified translators and revisions after feedback from an in-country linguistic consultant, the developerand three native physicians. The understanding and convenience of the translated version was evaluated using qualitative in-depth interviews with five patients with dyspnoea.
ResultsA Swedish version of the Dyspnoea-12 was elaborated and evaluated carefully according to international guidelines. The Swedish version, ‘Dyspné–12’, has the same layout as the original version, including 12 items distributed on seven physical and five affective items. The Dyspnoea-12 is copyrighted by the developer but can be used free of charge after permission for not industry-funded research.
ConclusionA Swedish version of the Dyspnoea-12 is now available for clinical validation and multidimensional measurement across diseases and settings with the aim of improved evaluation and management of dyspnoea.
Bacterial meningitis remains an important cause of morbidity and mortality worldwide. Its epidemiological characteristics, however, are changing due to new vaccines and secular trends. Conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae (10-valent) were introduced in 1986 and 2010 in Finland. We assessed the disease burden and long-term trends of five common causes of bacterial meningitis in a population-based observational study.
MethodsA case was defined as isolation of S. pneumoniae, Neisseria meningitidis, Streptococcus agalactiae, Listeria monocytogenes or H. influenzae from cerebrospinal fluid and reported to national, population-based laboratory surveillance system during 1995–2014. We evaluated changes in incidence rates (Poisson or negative binomial regression), case fatality proportions (2) and age distribution of cases (Wilcoxon rank-sum).
ResultsDuring 1995–2014, S. pneumoniae and N. meningitidis accounted for 78% of the total 1361 reported bacterial meningitis cases. H. influenzae accounted for 4% of cases (92% of isolates were non-type b). During the study period, the overall rate of bacterial meningitis per 1 00 000 person-years decreased from 1.88 cases in 1995 to 0.70 cases in 2014 (4% annual decline (95% CI 3% to 5%). This was primarily due to a 9% annual reduction in rates of N. meningitidis (95% CI 7% to 10%) and 2% decrease in S. pneumoniae (95% CI 1% to 4%). The median age of cases increased from 31 years in 1995–2004 to 43 years in 2005–2014 (p=0.0004). Overall case fatality proportion (10%) did not change from 2004 to 2009 to 2010–2014.
ConclusionsSubstantial decreases in bacterial meningitis were associated with infant conjugate vaccination against pneumococcal meningitis and secular trend in meningococcal meningitis in the absence of vaccination programme. Ongoing epidemiological surveillance is needed to identify trends, evaluate serotype distribution, assess vaccine impact and develop future vaccination strategies.
Although many secondary effects of high levels of vanadium (V) and chromium (Cr) overlap with symptoms seen in paediatric patients with chronic kidney disease (CKD), their plasma V and Cr levels are understudied.
DesignAncillary cross-sectional study to a prospective, longitudinal, randomised controlled trial.
SettingChildren’s Hospital of Western Ontario, London Health Sciences Centre, London, Ontario, Canada.
Participants36 children and adolescents 4–18 years of age with CKD.
Interventions1–6 trace element measurements per patient. Cystatin C (CysC) estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma V and Cr levels were measured using high-resolution sector field inductively coupled mass spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart programme. Water Cr and V data were obtained from the Ontario Water (Stream) Quality Monitoring Network.
Primary and secondary outcome measuresPrimary outcomes: plasma Cr and V. Secondary outcomes: age, season, CysC, CysC eGFR, and Cr and V levels in environmental water.
ResultsThe median (IQR) eGFR was 51 mL/min/1.73 m2 (35, 75). The median V level was 0.12 µg/L (0.09, 0.18), which was significantly greater than the 97.5th percentile of the reference interval of 0.088 µg/L; 32 patients had at least one set of V levels above the published reference interval. The median Cr level was 0.43 µg/L (0.36, 0.54), which was also significantly greater than the established reference interval; 34 had at least one set of Cr levels above the published reference interval. V and Cr levels were moderately correlated. Only some patients had high environmental exposure.
ConclusionsOur study suggests that paediatric patients with CKD have elevated plasma levels of V and Cr. This may be the result of both environmental exposure and a low eGFR. It may be necessary to monitor V and Cr levels in patients with an eGFR <30 mL/min/1.73 m2.
Trial registration numberNCT02126293; HC#172241.
This study aimed to investigate the prospective influence of multisite pain, depression, anxiety, self-rated health and pain-related disability on recovery from chronic low back pain (LBP).
SettingThe data is derived from the second (1995–1997) and third (2006–2008) wave of the Nord-Trøndelag Health Study (HUNT) in Norway.
ParticipantsThe study population comprises 4484 women and 3039 men in the Norwegian HUNT Study who reported chronic LBP at baseline in 1995–1997.
Primary outcome measuresThe primary outcome was recovery from chronic LBP at the 11-year follow-up. Persons not reporting pain and/or stiffness for at least three consecutive months during the last year were defined as recovered. A Poisson regression model was used to estimate adjusted risk ratios (RRs) with 95% CIs.
ResultsAt follow-up, 1822 (40.6%) women and 1578 (51.9%) men reported recovery from chronic LBP. The probability of recovery was inversely associated with number of pain sites (P-trend<0.001). Compared with reporting 2–3 pain sites, persons with only LBP had a slightly higher probability of recovery (RR 1.10, 95% CI 0.98 to 1.22 in women and RR 1.10, 95% CI 1.01 to 1.21 in men), whereas people reporting 6–9 pain sites had substantially lower probability of recovery (RR 0.58, 95% CI 0.52 to 0.63 in women and RR 0.70, 95% CI 0.63 to 0.79 in men). Poor/not so good self-rated general health, symptoms of anxiety and depression, and pain-related disability in work and leisure were all associated with reduced probability of recovery, but there was no statistical interaction between multisite pain and these comorbidities.
ConclusionsIncreasing number of pain sites was inversely associated with recovery from chronic LBP. In addition, factors such as poor self-rated health, psychological symptoms and pain-related disability may further reduce the probability of recovery from chronic LBP.
Survivors of muscle invasive bladder cancer (MIBC) experience physical and psychosocial side effects of cancer diagnosis and treatment. These negative side effects have a crucial impact on their health-related quality of life (HRQoL). To date, there is evidence that rehabilitation interventions such as physical activity and psychosocial support have a positive effect on the HRQoL of cancer survivors. Unfortunately, there are no specific guidelines for rehabilitation or survivorship programmes for MIBC survivors. Therefore, this systematic review aims to assess the effects of exercise-based and psychosocial rehabilitation interventions in MIBC survivors.
Methods and analysisThe approach of this review is consistent with the Cochrane methodology. Randomized controlled trials and non-randomised studies will be included. The population of interest is patients (≥18 years of age) with diagnosis of MIBC or high-risk non-MIBC for whom a radical cystectomy is indicated. There will be two eligible intervention types for inclusion: exercise-based and psychosocial rehabilitation interventions. The primary outcome measures are patient-reported outcomes (eg, HRQoL, fatigue and pain) and physical fitness. Studies will be identified independently by two review authors by searching the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Web of Science and the Physiotherapy Evidence Database. A third reviewer will be asked by disagreements. Risk of bias will be assessed using the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. Data will be summarised descriptively. If homogeneity of the studies is sufficient, meta-analysis will be undertaken. The broad scope of this review (ie, different interventions and study designs) is needed to have a comprehensive view on effective rehabilitation interventions.
Ethics and disseminationEthics approval is not required, as no primary data will be collected. Results will be disseminated through a peer-reviewed publication.
Alcohol consumption creates a significant public health burden, and young people who drink alcohol place themselves at risk of harm. Expert guidance and reviews have highlighted the pressing need for reliable and valid, age-appropriate alcohol screening and assessment measures for young people. The proposed systematic review will evaluate existing alcohol screening and assessment measures for young people aged 24 and under.
Methods and analysisSix electronic databases will be searched for published and grey literature. In addition, reverse and forward citation searching and consultation with experts will be performed. Three sets of search terms will be combined, including alcohol use/problems, young people and validation studies. The titles and abstracts of reports from the searches will be screened, and potentially relevant full-text reports will be retrieved and independently assessed for inclusion by two reviewers based on prespecified criteria. Discrete validation studies within included reports will then be assessed for eligibility. There will be an a priori basic quality threshold for predictive validity, internal and test–retest for studies to warrant full data extraction. Studies above the quality threshold will be assessed for quality using the modified consensus-based standards for the selection of health measurement instruments checklist and a quality assessment tool for diagnostic accuracy studies.
DisseminationThis review will highlight the best performing measures both for screening and assessment based on their psychometric properties and the quality of the validation studies supporting their use. Providing clear guidance on which existing measures perform best to screen and assess alcohol use and problems in young people will inform policy, practice and decision-making, and clarify the need for further research.
Trial registration numberInternational Prospective Register of Systematic Reviews, CRD42016053330.
Guided internet-based intervention beyond hearing aid (HA) fitting has been shown to be efficacious in randomised controlled trials (RCTs). However, internet interventions have rarely been applied clinically as a part of regular aural rehabilitation (AR). Our aim was to evaluate the effectiveness of internet-based AR for HA users from a clinical population.
Outcome measuresThe Hearing Handicap Inventory for the Elderly (HHIE) was used as the primary outcome measure, and the Communication Strategies Scale (CSS) and the Hospital Anxiety and Depression Scale were used as secondary outcome measures. All questionnaires were administered before and directly after the intervention and at 6 months postintervention.
MethodsWe used a parallel group design (RCT). The data were collected in 2013–2014 at three different clinics. Seventy-four HA users were randomly assigned to receive either full internet-based AR (intervention group, n=37) or one element of the internet-based AR (control group, n=37).
ResultsData were analysed following the intention-to-treat principle. Each group showed improved HHIE scores over time and did not differ significantly from each other. The intervention group showed significantly greater improvement compared with the control group for the CSS total and the non-verbal subscale scores. The intervention group and control group were also subdivided into two age groups: 20–59 years and 60–80 years. Significantly better improvement on the CSS total and non-verbal subscale scores was found in the older group compared with the younger participants.
ConclusionsThis study indicates that participants in an internet-based intervention applied in general clinical practice showed improved self-reported communication skills compared with a control group. Receiving a full intervention was not more effective in improving self-reported hearing problems than receiving just one element of the internet-based intervention.
Trial registration numberThis trial is registered at ClinicalTrals.gov, NCT01837550; results.
Despite positive health outcomes associated with advance care planning (ACP), little research has investigated the impact of ACP in surgical populations. Our goal is to evaluate how an ACP intervention video impacts the patient centredness and ACP of the patient-surgeon conversation during the presurgical consent visit. We hypothesise that patients who view the intervention will engage in a more patient-centred communication with their surgeons compared with patients who view a control video.
Methods and analysisRandomised controlled superiority trial of an ACP video with two study arms (intervention ACP video and control video) and four visits (baseline, presurgical consent, postoperative 1 week and postoperative 1 month). Surgeons, patients, principal investigator and analysts are blinded to the randomisation assignment.
SettingSingle, academic, inner city and tertiary care hospital. Data collection began July 16, 2015 and continues to March 2017.
ParticipantsPatients recruited from nine surgical oncology clinics who are undergoing major cancer surgery.
InterventionsIn the intervention arm, patients view a patient preparedness video developed through extensive engagement with patients, surgeons and other stakeholders. Patients randomised to the control arm viewed an informational video about the hospital surgical programme.
Main outcomes and measuresPrimary Outcome: Patient centredness and ACP of patient-surgeon conversations during the presurgical consent visit as measured through the Roter Interaction Analysis System. Secondary outcomes: patient Hospital Anxiety and Depression Scale score; patient goals of care; patient, companion and surgeon satisfaction; video helpfulness; medical decision maker designation; and the frequency patients watch the video. Intent-to-treat analysis will be used to assess the impact of video assignment on outcomes. Sensitivity analyses will assess whether there are differential effects contingent on patient or surgeon characteristics.
Ethics and disseminationThis study has been approved by the Johns Hopkins School of Medicine institutional review board and is registered on clinicaltrials.gov (NCT02489799, First received: July 1, 2015).
Trial registration numberclinicaltrials.gov, NCT02489799.
Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. Real world data on efficacy and safety of TNF-α blockers in the elderly with PsA are lacking. The aim of this study was to evaluate the effectiveness, through the achievement of minimal disease activity (MDA), drug discontinuation rate, and safety in elderly patients with PsA on TNF-α blockers. A multicenter, observational study was carried out in four Italian centers. The assessment of disease activity and safety were performed at the start of anti-TNF-α (T0), at 6 months (T6) and at 12 months (T12). A total of 145 PsA patients were included in the study. At baseline 68 (46.9%) patients were on etanercept, 60 (41.3%) on adalimumab, 11 (7.6%) on golimumab, and 6 (4.1%) on infliximab. All the variables concerning PsA activity showed a statistically significant improvement when comparing T6 and T12 with T0. After 6 and 12 months of therapy, respectively, 31 (22.6%) and 71 (51.8%) patients achieved MDA (p < 0.001). The drug discontinuation rate was 5.5% with a mean of 6.8 months (range 2–10 months), and it was due to lack of efficacy, adverse events, and lost to follow-up. Nine patients (6.2%) reported the onset of mild infections resolved with antimicrobial specific oral regimen without therapy interruption. TNF-α blockers are effective in the achievement of a low disease status and safe in elderly patients with PsA. Therefore, age should not be considered a limitation to their use.
The utility of performing blood cultures in patients with a suspected skin infection is debated. We investigated the association between blood culture positivity rates and patients' clinical condition, including acute disease severity and comorbidity. We performed a retrospective study, including patients with cellulitis and wound infection who had been enrolled in three Dutch multicenter studies between 2011 and 2015. Patients' acute clinical condition was assessed using the Modified Early Warning Score (MEWS; severe: MEWS ≥2) and comorbidity with the Charlson Comorbidity Index (CCI; severe: CCI ≥2). A total of 334 patients with a suspected skin infection were included. Blood cultures were performed in 175 patients (52%), 28 of whom (16%) had a positive blood culture. Data on the clinical condition were collected in 275 patients. Blood cultures were performed in 76% of the patients with a severe acute condition, compared with 48% with a non-severe acute condition (OR 3.5; 95% confidence interval: 2.0–6.2; p < 0.001). Blood cultures were positive in 18% and 12% respectively (OR 1.7 (0.7–4.1); p = 0.3). Blood cultures were performed in 53% of patients with severe comorbidity, compared with 61% without severe comorbidity (OR 0.7; 0.4–1.2; p = 0.2). Blood cultures were positive in 25% and 10% respectively (OR = 3.1; 1.2–7.5; p = 0.02). The blood culture positivity rate among hospitalized patients diagnosed with skin infections was higher than the rates reported by the Infectious Diseases Society of America guidelines, particularly in patients with severe comorbidity. Therefore, the recommendations concerning blood culture performance in patients with a skin infection should be reconsidered.
It is possible -- such is the argument of Carter Findley in his Turks in World History -- that in doing so it drew on a long Turkish cultural tradition, born in Central Asia and predating conversion to Islam, that figured a sacralisation of the state, which has vested its modern signifier, devlet, with an aura of unusual potency.
You may be wondering what the heck a congenital variant of spinal segmentation has to do with religion. From the always-excellent Online Etymology Dictionary:
Bone at the base of the spine, 1753, from Late Latin os sacrum "sacred bone," from Latin os "bone" + sacrum, neuter of sacer "sacred" (see sacred). Said to be so called because the bone was the part of animals that was offered in sacrifices. Translation of Greek hieron osteon. Greek hieros also can mean "strong," and some sources suggest the Latin is a mistranslation of Galen, who was calling it "the strong bone."