bluuebunny/crossref_metadata_2025 huggingface dataset:
A multinational, drug utilization study to investigate the use of dexmedetomidine (Dexdor®) in clinical practice in the EU
Authors: Weatherall Mary , Aantaa Riku , Conti Giorgio , Garratt Chris , Pohjanjousi Pasi , Lewis Michael A. , Moore Nicholas , Perez‐Gutthann Susana
Published: March 2017

Aims

Dexmedetomidine (dexdor®) is approved in the European Union (EU) for sedation of adults in the intensive care unit (ICU). The present observational, retrospective study was requested by the European Medicines Agency to investigate dexmedetomidine use in clinical practice, with a particular focus on off‐label use, including the paediatric population.

Methods

Study countries and sites were chosen from those with highest dexmedetomidine use, based on sales. Site selection (blind) was conducted by a multispecialist, independent group. Anonymized data on demographics, treatment indication, dexmedetomidine dosing, concomitant medications and treatment effectiveness were collected retrospectively from records of all dexmedetomidine‐treated patients at the site during the enrolment period. Informed consent was waived, to avoid influencing the prescribing of dexmedetomidine. Recruitment was completed within 18 months of first site initiation.

Results

Data from 2000 patients were collected from 16 hospitals in four EU countries (Finland 750, Poland 505, Germany 470, Austria 275). The median age was 62 years, with more males (70.2%) than females. Dexmedetomidine was primarily used in the adult ICU (86.0%) for ICU sedation (78.6%) and mostly dosed according the product label. The intended sedative effect was obtained in 84.9% of administrations. Paediatric use (5.9% of patients, mostly in Austria and Finland) occurred mainly in the adult or paediatric ICU (75.6%) for sedation (67.2%).

Conclusions

Overall, most patients were treated with dexmedetomidine according to the product labelling. Use in children was limited but significant and similar in scope to that in adults. Administrations not fully according to the product labelling usually occurred in an ICU environment and reflected extensively investigated clinical uses of dexmedetomidine.
Simvastatin reduces vaso‐occlusive pain in sickle cell anaemia: a pilot efficacy trial
Authors: Hoppe Carolyn , Jacob Eufemia , Styles Lori , Kuypers Frans , Larkin Sandra , Vichinsky Elliott
Published: March 2017

Sickle cell anaemia (SCA) is a progressive vascular disease characterized by episodic vaso‐occlusive pain. Despite the broad impact of inflammation on acute and chronic clinical manifestations of SCA, no directed anti‐inflammatory therapies currently exist. Statins are cholesterol‐lowering agents shown to confer protection from vascular injury by suppressing inflammation. We previously documented a reduction in soluble biomarkers of inflammation in patients with sickle cell disease treated with simvastatin. To determine the potential clinical efficacy of simvastatin, we treated 19 SCA patients with single daily dose simvastatin for 3 months and assessed changes from baseline in the frequency and intensity of diary‐reported pain and levels of circulating nitric oxide metabolites (NOx), high sensitivity C‐reactive protein (hs‐CRP), vascular cell adhesion molecule 1 (VCAM‐1), intercellular adhesion molecule 1 (ICAM‐1), ICAM‐3, E‐selectin, and vascular endothelial growth factor (VEGF). Treatment with simvastatin resulted in a significant reduction in the frequency of pain (P = 0·0003), oral analgesic use (P = 0·003) and circulating hs‐CRP (P = 0·003), soluble (s)E‐selectin (P = 0·01), sICAM‐1 (P = 0·02), sICAM‐3 (P = 0·02) and sVEGF (P = 0·01). Simvastatin had no effect on pain intensity or levels of NOx, sP‐selectin and sVCAM‐1. The observed reductions in pain rate and markers of inflammation were greatest in subjects receiving hydroxycarbamide (HC), suggesting a synergistic effect of simvastatin. These results provide preliminary clinical data to support a larger trial of simvastatin in SCA.
Lichenoid folliculitis: A unifying concept
Authors: Turegano Mamina M. , Sperling Leonard C.
Published: March 2017

Skin diseases presenting with keratotic papules, atrophy, cicatricial alopecia and/or “lichenoid” histopathologic changes have been described under at least 30 names. This family of diseases contains 2 subgroups, largely based on clinical features: keratosis pilaris atrophicans (KPA; including keratosis pilaris atrophicans faciei/ulerythema ophryogenes, atrophoderma vermiculatum, and keratosis follicularis spinulosa decalvans); and the lichen planopilaris (LPP) subgroup (including LPP, frontal fibrosing alopecia, Graham‐Little‐Piccardi‐Lassueur Syndrome and fibrosing alopecia in a pattern distribution). An interface dermatitis with lichenoid inflammation is characteristic of the LPP group of disorders, but the literature provides scant information about the histopathology of the KPA group. Our experience has been that the 2 subgroups show a unifying histologic similarity as well as considerable clinical overlap. Because these conditions overlap clinically and histologically, we propose that the term lichenoid folliculitis (LF) be used to refer to this group of diseases, thus simplifying cumbersome nomenclature and highlighting the possibility of shared pathogenesis and treatment options.
Short‐term effects of a low carbohydrate diet on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes: A randomized open‐label crossover trial
Authors: Ranjan Ajenthen , Schmidt Signe , Damm‐Frydenberg Camilla , Holst Jens Juul , Madsbad Sten , Nørgaard Kirsten
Published: March 2017

The aim of the present study was to assess the effects of a high carbohydrate diet (HCD) vs a low carbohydrate diet (LCD) on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes. Ten patients (4 women, insulin pump‐treated, median ± standard deviation [s.d.] age 48 ± 10 years, glycated haemoglobin [HbA1c] 53 ± 6 mmol/mol [7.0% ± 0.6%]) followed an isocaloric HCD (≥250 g/d) for 1 week and an isocaloric LCD (≤50 g/d) for 1 week in random order. After each week, we downloaded pump and sensor data and collected fasting blood and urine samples. Diet adherence was high (225 ± 30 vs 47 ± 10 g carbohydrates/d; P < .0001). Mean sensor glucose levels were similar in the two diets (7.3 ± 1.1 vs 7.4 ± 0.6 mmol/L; P = .99). The LCD resulted in more time with glucose values in the range of 3.9 to 10.0 mmol/L (83% ± 9% vs 72% ± 11%; P = .02), less time with values ≤3.9 mmol/L (3.3% ± 2.8% vs 8.0% ± 6.3%; P = .03), and less glucose variability (s.d. 1.9 ± 0.4 vs 2.6 ± 0.4 mmol/L; P = .02) than the HCD. Cardiovascular markers were unaffected, while fasting glucagon, ketone and free fatty acid levels were higher at end of the LCD week than the HCD week. In conclusion, the LCD resulted in more time in euglycaemia, less time in hypoglycaemia and less glucose variability than the HCD, without altering mean glucose levels.
The impact of seizures on epilepsy outcomes: A national, community‐based survey
Authors: Josephson Colin B. , Patten Scott B. , Bulloch Andrew , Williams Jeanne V. A. , Lavorato Dina , Fiest Kirsten M. , Secco Mary , Jette Nathalie
Published: March 2017

Objective

The aim of this study was to examine the impact of seizures on persons living with epilepsy in a national, community‐based setting.

Methods

The data source was the Survey of Living with Neurological Conditions in Canada (SLNCC), a cohort derived from a national population‐based survey of noninstitutionalized persons aged 15 or more years. Participants had to be on a seizure drug or to have had a seizure in the past 5 years to meet the definition of active epilepsy. The respondents were further stratified by seizure status: the seizure group experienced ≥1 seizure in the past 5 years versus the no seizure group who were seizure‐free in the past ≥5 years regardless of medication status. Weighted overall and stratified prevalence estimates and odds ratios were used to estimate associations.

Results

The SLNCC included 713 persons with epilepsy with a mean age of 45.4 (standard deviation 18.0) years. Fewer people in the seizure group (42.7%) reported being much better than a year ago versus those in the no seizure group (70.1%). Of those with seizures, 32.1% (95% confidence interval [95% CI] 18.8–45.3) had symptoms suggestive of major depression (as per the Patient Health Questionnaire‐9) compared to 7.7% (95% CI 3.4–11.9) of those without seizures. Driving, educational, and work opportunities were also significantly limited, whereas stigma was significantly greater in those with seizures.

Significance

This community‐based study emphasizes the need for seizure freedom to improve clinical and psychosocial outcomes in persons with epilepsy. Seizure freedom has an important influence on overall health, as those with at least one seizure over the prior 5 years had an increased risk of mood disorders, worse quality of life, and faced significantly more stigma.
A critical analysis of the direct effects of dredging on fish
Authors: Wenger Amelia S. , Harvey Euan , Wilson Shaun , Rawson Chris , Newman Stephen J. , Clarke Douglas , Saunders Benjamin J. , Browne Nicola , Travers Michael J. , Mcilwain Jennifer L. , Erftemeijer Paul L. A. , Hobbs Jean‐Paul A. , Mclean Dianne , Depczynski Martial , Evans Richard D.
Published: March 2017

Dredging can have significant impacts on aquatic environments, but the direct effects on fish have not been critically evaluated. Here, a meta‐analysis following a conservative approach is used to understand how dredging‐related stressors, including suspended sediment, contaminated sediment, hydraulic entrainment and underwater noise, directly influence the effect size and the response elicited in fish across all aquatic ecosystems and all life‐history stages. This is followed by an in‐depth review summarizing the effects of each dredging‐related stressor on fish. Across all dredging‐related stressors, studies that reported fish mortality had significantly higher effect sizes than those that describe physiological responses, although indicators of dredge impacts should endeavour to detect effects before excessive mortality occurs. Studies examining the effects of contaminated sediment also had significantly higher effect sizes than studies on clean sediment alone or noise, suggesting additive or synergistic impacts from dredging‐related stressors. The early life stages such as eggs and larvae were most likely to suffer lethal impacts, while behavioural effects were more likely to occur in adult catadromous fishes. Both suspended sediment concentration and duration of exposure greatly influenced the type of fish response observed, with both higher concentrations and longer exposure durations associated with fish mortality. The review highlights the need for in situ studies on the effects of dredging on fish which consider the interactive effects of multiple dredging‐related stressors and their impact on sensitive species of ecological and fisheries value. This information will improve the management of dredging projects and ultimately minimize their impacts on fish.
Spaces of lobbying
Authors: Hofman Annelore , Aalbers Manuel B.
Published: March 2017

This paper departs from the observation that a systematic review of the available theories, concepts, and methods and techniques for researching lobbying is lacking. Lobbying is a relational geography of power. And although economic and political geographers study a range of practices that could be considered constitutive to lobbying, they have hitherto largely ignored the spaces of lobbying. We conceptualize lobbying as a practice of 3 flows between spaces of lobbying: the flows of people between organizations, the flows of ideas between these people, and the flows of resources between organizations. Lobbying is fundamental to understand the execution of power by firms towards a range of state actors, and understood as the directed actions of individuals and groups to alter, influence, or hamper the decision‐making process of governments; these actions consist of the mobilization of resources that activate power and enable access to spaces of lobbying. Access to different spaces of lobbying will influence the effectiveness of lobbying practices. Geographers are in a unique position to look at the mobilization of power through access to spaces of lobbying and its resources. We discuss how lobbying is supported by material and immaterial resources for the (re)production of spaces of lobbying. Finally, we present different methods and techniques to research lobbying.
A prospective study of health‐related quality of life of boys with severe haemophilia A in China: comparing on‐demand to prophylaxis treatment
Authors: Wu R. , Sun J. , Xiao J. , Liu Y. , Xue F. , Wang H. , Tang L. , Zhao Y. , Li K. , Yang R. , Hu Y. , Luke K.‐H. , Poon M.‐C. , Blanchette V. S. , Usuba K. , Young N. L.
Published: March 2017

Introduction

Treatment for boys with haemophilia in China is rapidly improving; however, comprehensive outcomes have not been examined prospectively.

Aim

The aim of this study was to evaluate the effect of short‐term full‐dose prophylaxis compared to on‐demand treatment, on the Health‐Related Quality of Life (HR‐QoL) of boys with severe haemophilia A (HA) in China.

Methods

Boys with severe HA (FVIII<1%) completed 3 months of on‐demand treatment and 3 months of full‐dose prophylaxis (25 FVIII IU per kg 3x per week). The primary outcomes were child‐ and parent‐reported Canadian Hemophilia Outcomes – Kids Life Assessment Tool (CHO‐KLAT) scores. The number and type of bleeds and Activities Scale for Kids (ASK) scores were also recorded.

Results

Analyses included 23 boys between 4 and 15.9 years of age. The number of bleeds decreased by 94% on prophylaxis (P < 0.0001, Wilcoxon Signed‐Rank test). The mean child‐reported CHO‐KLAT scores for boys ≥7 years (n = 20) was 61.4 (±10.9) during on‐demand treatment and 61.9 (±11.4) following short‐term prophylaxis (P = 0.72, paired t‐test). The mean parent‐reported CHO‐KLAT score during the on‐demand phase was 54.4 (±10.5) with an increase of 3.8 points (±8.1; P = 0.04, paired t‐test) following prophylaxis.

Conclusions

Child‐reported CHO‐KLAT scores were lower in boys with severe HA in China than reported in countries with access to full‐dose prophylaxis. Boys reported higher HR‐QoL scores than their parents. Small improvements in ASK scores were noted following the prophylaxis phase. These changes were only significant in the parent‐reported CHO‐KLAT scores. Longer term prospective clinical trials are needed in China to determine the impact of prophylaxis on HR‐QoL in boys with severe HA.
Severe bleeding diatheses in an elderly patient with combined type autoantibody against factor XIII A subunit; novel approach to the diagnosis and classification of anti‐factor XIII antibodies
Authors: Kun M. , Szuber N. , Katona É. , Pénzes K. , Bonnefoy A. , Bécsi B. , Erdődi F. , Rivard G. E. , Muszbek L.
Published: March 2017

Introduction

Acquired factor XIII (FXIII) deficiency due to autoantibody is a rare, severe bleeding diathesis. Its laboratory diagnosis and classification represents a difficult task.

Aim

Introduction of novel approaches into the diagnosis and characterization of anti‐FXIII autoantibody and demonstration of their use in the diagnosis of a patient with autoimmune FXIII deficiency.

Methods

Factor XIII activity, FXIII antigen levels and the titre of anti‐FXIII‐A antibody were monitored throughout the course of the disease. FXIII activity was measured by ammonia release assay; FXIII‐A2B2 complex, total and free FXIII‐B concentrations were determined by ELISAs. The binding constant for the interaction of the autoantibody with recombinant FXIII‐A2 (rFXIII‐A2) and FXIII‐A2B2 was determined by surface plasmon resonance (SPR). The inhibitory capacity of IgG was expressed as the concentration exerting 50% inhibition of FXIII activation/activity (IC50). The truncation of FXIII‐A by thrombin was monitored by western blotting. The inhibition of Ca2+ ‐induced FXIII activation and active FXIII (FXIIIa) were assessed by FXIII activity assay.

Results

The antibody bound to rFXIII‐A2 and FXIII‐A2B2 with high affinity and accelerated the decay of supplemented FXIII concentrate. An IC50 value of 170.1 μg IgG·mL−1 indicated effective FXIII neutralization. The main neutralizing effect of the autoantibody was the inhibition of FXIIIa. After 2 months, due to combined therapeutic modalities, the autoantibody disappeared and FXIII activity significantly elevated.

Conclusion

The anti‐FXIII‐A autoantibody exerted a combined effect including inhibition of FXIIIa and acceleration of FXIII decay in the plasma. IC50 and binding constant determinations added important information to the characterization of the autoantibody.
Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement
Authors: Iorio A. , Iserman E. , Blanchette V. , Dolan G. , Escuriola Ettingshausen C. , Hermans C. , Negrier C. , Oldenburg J. , Reininger A. , Rodriguez‐Merchan C. , Spannagl M. , Valentino L. A. , Young G. , Steinitz‐Trost K. N. , Gringeri A.
Published: March 2017

Background

Prophylactic replacement with factor concentrate is the optimal treatment for persons with severe haemophilia to avoid or minimize bleeding. This ultimately prevents or reduces joint disease and improves life expectancy and quality of life towards values matching those in the normal population. However, uncertainty still exists around the optimal regimens to be prescribed for prophylaxis. An increasing number of treating physicians and patients are showing interest in patient‐tailored approaches to prophylaxis, which aim to harmonize the prophylaxis regimen with the patients’ bleeding phenotype, levels of physical activity and a variety of other variables.

Methods

A modified Delphi technique was adopted to generate consensus. The expert panel met in person to set the objectives, be trained on the Delphi technique and agree on the desired level of consensus. Three iterations were used to identify the targets, the scenarios and their combinations.

Results

Twenty‐eight scenarios and eight target levels were identified and used to issue recommendations. The panel reached the desired level of consensus on positive or negative recommendations. Areas where consensus was not reached were identified and proposed as areas for future research. Prospective assessment of the validity of most of the proposed targets is recommended.

Conclusions

We have generated, by expert consensus, target plasma levels of factor concentrate to be used to tailor treatment for persons with haemophilia.
A prospective evaluation of levofloxacin‐based triple therapy for refractory Helicobacter pylori infection in Australia
Authors: Katelaris Peter H. , Katelaris Anthea L.
Published: March 2017

Background

First‐line Helicobacter pylori eradication failure is a common and challenging problem.

Aim

To assess the efficacy of salvage levofloxacin‐based triple therapy in Australia.

Methods

Prospective patients referred after prior treatment failure(s) were prescribed esomeprazole 40 mg, amoxicillin 1 g and levofloxacin 500 mg each twice daily for 10 days. All patients received detailed written and verbal adherence support. Outcome assessment was by
13C‐urea breath test and/or histology and urease test.

Results

In 150 consecutive, evaluable patients (66% female, mean age 54 ± 14 years; six smokers), the main indications for treatment were peptic ulcer disease (17%), increased gastric cancer risk (20%), symptoms (35%) and other risk reduction (28%). The median number of previous treatments was 2 (range 1–7). Eradication of H. pylori was achieved in 90% (intention to treat (ITT)) and 91% (per‐protocol (PP)) of patients. The eradication rate did not differ according to the type or number of prior treatments: 93% when ≤2 (n = 107) compared with 84% after three or more prior treatments (n = 43; P = 0.13) or with age, ethnicity or indication for treatment but it was higher in females (ITT 94 vs 82%, P = 0.04). Adherence was excellent (95%). No serious adverse effects were observed; mild adverse effects were reported in 11%. No primary levofloxacin resistance was observed in 20 concurrent cases.

Conclusion

The efficacy and safety of this levofloxacin‐based triple therapy suggests it should be used as a salvage regimen in this region. Randomised comparative trials are unlikely to be done but these data compare favourably with local data for other salvage therapies.
Purebreeding of Red Maasai and crossbreeding with Dorper sheep in different environments in Kenya
Authors: Zonabend König E. , Strandberg E. , Ojango J.M.K. , Mirkena T. , Okeyo A.M. , Philipsson J.
Published: March 2017

The aim of this article was to study opportunities for improvement of the indigenous and threatened Red Maasai sheep (RM) in Kenya, by comparing purebreeding with crossbreeding with Dorper sheep (D) as a terminal breed, in two different environments (Env. A and a harsher Env. B), assuming different levels of genotype‐by‐environment interaction (G × E). Breeding goals differed between environments and breeds. Four scenarios of nucleus breeding schemes were stochastically simulated, with the nucleus in Env. A. Overall, results showed an increase in carcass weight produced per ewe by more than 10% over 15 years. Genetic gain in carcass weight was 0.17 genetic SD/year (0.2 kg/year) across scenarios for RM in the less harsh Env. A. For survival and milk yield, the gain was lower (0.04–0.05 genetic SD/year). With stronger G × E, the gain in the commercial tier for RM in the harsher Env. B became increasingly lower. Selection of females also within the commercial tier gave slightly higher genetic gain. The scenario with purebreeding of RM and a subnucleus in Env. B gave the highest total income and quantity of meat. However, quantity of meat in Env. A increased slightly from having crossbreeding with D, whereas that in Env. B decreased. A simple and well‐designed nucleus breeding programme would increase the genetic potential of RM. Crossbreeding of RM with D is not recommended for harsh environmental conditions due to the large breed differences expected in that environment.
Association between diabetes mellitus/hyperglycaemia and peri‐implant diseases: Systematic review and meta‐analysis
Authors: Monje Alberto , Catena Andres , Borgnakke Wenche S.
Published: March 2017

Aim

This systematic review investigates whether hyperglycaemia/diabetes mellitus is associated with peri‐implant diseases (peri‐implant mucositis and peri‐implantitis).

Materials and Methods

Electronic and manual literature searching was conducted. An a priori case definition for peri‐implantitis was used as an inclusion criterion to minimize risk of bias. The Newcastle‐Ottawa Scale was used for quality assessment; random effect models were applied; and results were reported according to the PRISMA Statement.

Results

Twelve studies were eligible for qualitative and seven of them for quantitative analyses. Meta‐analyses detected the risk of peri‐implantitis was about 50% higher in diabetes than in non‐diabetes (RR = 1.46; 95% CI: 1.21–1.77 and OR = 1.89; 95% CI: 1.31–2.46; z = 5.98; p < .001). Importantly, among non‐smokers, those with hyperglycaemia had 3.39‐fold higher risk for peri‐implantitis compared with normoglycaemia (95% CI: 1.06–10.81). Conversely, the association between diabetes and peri‐implant mucositis was not statistically significant (RR = 0.92; 95% CI: 0.72–1.16 and OR = 1.06; 95% CI: 0.84–1.27; z = 1.06, p = .29).

Conclusions

Within its limits that demand great caution when interpreting its findings, this systematic review suggests that diabetes mellitus/hyperglycaemia is associated with greater risk of peri‐implantitis, independently of smoking, but not with peri‐implant mucositis.
Tooth loss in generalized aggressive periodontitis: Prognostic factors after 17 years of supportive periodontal treatment
Authors: Graetz Christian , Sälzer Sonja , Plaumann Anna , Schlattmann Peter , Kahl Maren , Springer Claudia , Dörfer Christof , Schwendicke Falk
Published: March 2017

Aim

This retrospective longitudinal study assessed the risk of and prognostic factors for tooth loss in patients with generalized aggressive periodontitis (GAgP) after periodontal treatment in a university setting.

Methods

Fifty‐seven patients (1,505 teeth) were examined before (T0) and after active periodontal therapy (APT, T1) as well as after 17.4 ± 4.8 [range: 9–28] years of supportive periodontal therapy (SPT, T2). Descriptive statistics and a Cox‐proportional‐hazards shared‐frailty model were applied.

Results

Overall, 98 and 134 teeth were lost during APT and SPT, respectively, with 0.14 ± 0.18 teeth being lost per patient and year. During SPT, three patients (5%) lost ≥10 teeth, 14 (25%) lost 4–9 teeth, 40 lost 0–3 (70%) teeth, respectively. One‐third (n = 19) of all patients lost no teeth. Mean PPD of the teeth surviving SPT was stable from T1 (3.5 ± 1.1 mm) to T2 (3.4 ± 1.1 mm). Nearly, 84% of all survived teeth showed stable or improved bone level at T2. Risk of tooth loss was significantly increased in active smokers (HR[95% CI]: 4.94[1.91/12.75]), the upper dental arch (1.94[1,16/3.25]), with each mm of residual PPD (1.41[1.29/1.53]), teeth with furcation involvement (FI) (HR 4.00–4.44 for different degrees) and mobility (5.39 [2.06/14.1] for degree III).

Conclusion

Within the provided conservative treatment regimen, GAgP patients lost only few teeth.
A survey of clinicians regarding respiratory physiotherapy intervention for intubated and mechanically ventilated patients with community‐acquired pneumonia. What is current practice in Australian ICUs?
Authors: van der Lee Lisa , Hill Anne‐Marie , Patman Shane
Published: March 2017

Rationale, aims, and objectives

Community‐acquired pneumonia (CAP) is a common cause for intensive care unit (ICU) admission resulting in high morbidity and mortality. There is a paucity of evidence regarding respiratory physiotherapy for intubated and mechanically ventilated patients with CAP, and anecdotally clinical practice is variable in this cohort. The aims of this study were to identify the degree of variability in physiotherapy practice for intubated adult patients with CAP and to explore ICU physiotherapist perceptions of current practice for this cohort and factors that influence physiotherapy treatment mode, duration, and frequency.

Method

A survey was developed based on common aspects of assessment, clinical rationale, and intervention for intubated and mechanically ventilated patients. Senior ICU physiotherapists across 88 Australian public and private hospitals were recruited.

Results

The response rate was 72%. Respondents (n = 75) stated their main rationale for providing a respiratory intervention were improved airway clearance (98%, n = 60/61), alveolar recruitment (74%, n = 45/61), and gas exchange (33%, n = 20/61). Respondents estimated that average intervention lasted between 16 and 30 minutes (70% of respondents, n = 41/59) and would be delivered once (44%) or twice (44%) daily. Results indicated large variability in reported practice; however, trends existed regarding positioning in alternate side‐lying (81%, n = 52/64) or affected lung uppermost (83%, n = 53/64) and use of hyperinflation techniques (81%, 52/64). Decisions regarding duration were reported to be based on sputum volume (95%), viscosity (93%) and purulence (88%), cough effectiveness (95%), chest X‐ray (87%), and auscultation (84%). Sixty percent reported that workload and staffing affected intervention duration and frequency. Intervention time was more likely increased when there was greater staffing (P = .03).

Conclusion

Respiratory physiotherapy treatment varies for intubated patients with CAP. Further research is required to determine what is considered best practice for this patient population.
Restraint Use in Older Adults Receiving Home Care
Authors: Scheepmans Kristien , Dierckx de Casterlé Bernadette , Paquay Louis , Van Gansbeke Hendrik , Milisen Koen
Published: March 2017

Objectives

To determine the prevalence, types, frequency, and duration of restraint use in older adults receiving home nursing care and to determine factors involved in the decision‐making process for restraint use and application.

Design

Cross‐sectional survey of restraint use in older adults receiving home care completed by primary care nurses.

Setting

Homes of older adults receiving care from a home nursing organization in Belgium.

Participants

Randomized sample of older adults receiving home care (N = 6,397; mean age 80.6; 66.8% female).

Measurements

For each participant, nurses completed an investigator‐constructed and ‐validated questionnaire collecting information demographic, clinical, and behavioral characteristics and aspects of restraint use. A broad definition of restraint was used that includes a range of restrictive actions.

Results

Restraints were used in 24.7% of the participants, mostly on a daily basis (85%) and often for a long period (54.5%, 24 h/d). The most common reason for restraint use was safety (50.2%). Other reasons were that the individual wanted to remain at home longer, which necessitated the use of restraints (18.2%) and to provide respite for the informal caregiver (8.6%). The latter played an important role in the decision and application process. The physician was less involved in the process. In 64.5% of cases, there was no evaluation after restraint use was initiated.

Conclusion

Use of restraints is common in older adults receiving home care nursing in Belgium. These results contribute to a better understanding of the complexity of use of restraints in home care, a situation that may be even more complex than in nursing homes and acute hospital settings.
RS9, a novel Nrf2 activator, attenuates light‐induced death of cells of photoreceptor cells and Müller glia cells
Authors: Inoue Yuki , Shimazawa Masamitsu , Noda Yasuhiro , Nagano Ryota , Otsuka Tomohiro , Kuse Yoshiki , Nakano Yukimichi , Tsuruma Kazuhiro , Nakagami Yasuhiro , Hara Hideaki
Published: March 2017

The retina is highly sensitive to oxidative stress because of its high consumption of oxygen associated with the phototransductional processes. Recent findings have suggested that oxidative stress is involved in the pathology of age‐related macular degeneration, a progressive degeneration of the central retina. A well‐known environmental risk factor is light exposure, as excessive and continuous light exposure can damage photoreceptors. Nuclear factor‐erythroid 2‐related factor 2 (Nrf2) is a transcriptional factor that controls antioxidative responses and phase 2 enzymes. Thus, we hypothesized that RS9, a specific activator of Nrf2, decreases light‐induced retinal cell death in vivo and in vitro. Nrf2 was detected in the nucleus of the 661W cells exposed to RS9 and also after light exposure, and the Nrf2‐antioxidant response element binding was increased in 661W cells after exposure to RS9. Consequentially, the expression of the phase 2 enzyme's mRNAs of Ho‐1, Nqo‐1, and Gclm genes was increased in 661W cells after exposure to RS9. Furthermore, RS9 decreased the light‐induced death of 661W cells (2500 lux, 24 h), and also reduced the functional damages and the histological degeneration of the nuclei in the outer nuclear layer or the retina in the in vivo studies (8000 lux, 3 h). Heme oxygenase‐1 was increased after light exposure, and Nrf2 was translocated into the nucleus after light exposure in vivo. Silencing of Ho‐1 reduced the protective effects of RS9 against light‐induced death of 661W cells. These findings indicate that RS9 has therapeutic potential for retinal diseases that are aggravated by light exposure.

image
Association between serum and oral matrix metalloproteinase‐8 levels and periodontal health status
Authors: Noack B. , Kipping T. , Tervahartiala T. , Sorsa T. , Hoffmann T. , Lorenz K.
Published: March 2017

Background and Objective

Matrix metalloproteinase‐8 (MMP‐8) is involved in a wide range of pathologies including periodontitis and cardiovascular diseases (CVD). The association between periodontitis and CVD has been repeatedly recognized. The aim of the study was to analyze to what extent circulating active MMP‐8 (aMMP‐8) is associated with periodontal disease status and oral fluid aMMP‐8 levels in otherwise healthy subjects.

Material and Methods

In a cross‐sectional study, aMMP‐8 was measured in serum of 59 volunteers, comprising 19 periodontally healthy subjects, 20 patients with gingivitis as well as 20 with periodontitis. All study subjects were characterized regarding aMMP‐8 concentrations in different oral fluids as well as clinically and microbiologically with respect to periodontal disease. aMMP‐8 levels in gingival crevicular fluid were measured using the enzyme‐linked immunosorbent assay. Saliva enzyme levels as well as circulating aMMP‐8 were determined by a time‐resolved immunofluorometric assay. Both methods utilized the same monoclonal antibodies. Correlation and regression analyses were performed to study the potential association between serum aMMP‐8 and oral parameters.

Results

Oral aMMP‐8 levels were significantly higher in patients with periodontitis compared to periodontally healthy or gingivitis subjects. Highest serum aMMP‐8 concentration was also found in the periodontitis group. The serum levels correlated significantly with oral aMMP‐8 as well as with clinical parameters in a dose‐dependent manner. These results were confirmed in a multivariate regression analysis. After adjusting for potential confounders, saliva aMMP‐8 concentrations as well as periodontitis severity were significant predictors of serum aMMP‐8.

Conclusion

The associations between circulating aMMP‐8 and oral aMMP‐8 as well as periodontal findings in a dose‐dependent manner may contribute to linking periodontal disease with increased CVDsusceptibility.
Biodegradable gelatin/beta‐tricalcium phosphate sponges incorporating recombinant human fibroblast growth factor‐2 for treatment of recession‐type defects: A split‐mouth study in dogs
Authors: Shujaa Addin A. , Akizuki T. , Hoshi S. , Matsuura T. , Ikawa T. , Fukuba S. , Matsui M. , Tabata Y. , Izumi Y.
Published: March 2017

Background and Objective

Tissue engineering by using recombinant human (rh) growth factor technology may offer a promising therapeutic approach for treatment of gingival recession. Fibroblast growth factor‐2 (FGF‐2) has shown the ability to promote periodontal regeneration. Gelatin/beta‐tricalcium phosphate (gelatin/β‐TCP) sponges have been developed to control the release of growth factors. The present study evaluated the periodontal regenerative efficacy of rhFGF‐2 by comparing gelatin/β‐TCP sponges incorporated with rhFGF‐2 to the scaffolds alone in artificially created recession‐type defects in dogs.

Material and methods

Critically sized buccal gingival recession defects were surgically created on maxillary canine teeth of five dogs. In each animal, defects were randomized to receive either a gelatin/β‐TCP sponge soaked with rhFGF‐2 (gelatin/β‐TCP/rhFGF‐2) or phosphate‐buffered saline (gelatin/β‐TCP). Eight weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography and histological analyses.

Results

Complete root coverage was achieved in both groups. Microcomputed tomography revealed significantly greater new bone volume in the gelatin/β‐TCP/rhFGF‐2 group. Histologically, both groups achieved periodontal regeneration; however, gelatin/β‐TCP/rhFGF‐2 sites exhibited more tissue regeneration, characterized by significantly larger amounts of new cementum and new bone. Gelatin/β‐TCP sites featured increased long junctional epithelium and connective tissue attachment. In the gelatin/β‐TCP/rhFGF‐2 sites, new bone exhibited many haversian canals and circumferential lamellae as well as remarkably thick periosteum with blood vascularization and hypercellularity.

Conclusion

Within the limitations of this study, rhFGF‐2 in gelatin/β‐TCP sponges exhibits an increased potential to support periodontal wound healing/regeneration in canine recession‐type defects.
Treatment with direct‐acting antiviral agents of hepatitis C virus infection in injecting drug users: A prospective study
Authors: Boglione L. , Mornese Pinna S. , De Nicolò A. , Cusato J. , Cariti G. , Di Perri G. , D'Avolio A.
Published: March 2017

In this prospective study, we evaluated the effectiveness and tolerability of novel therapies against hepatitis C virus (HCV) in a cohort of PWID enrolled at our centre from April 2015 to July 2016. In this analysis, a total of 174 patients were included: eleven (6.3%) were treated with pegylated interferon (PEG‐IFN) and ribavirin (RBV) containing regimens, 163 (93.7%) with IFN‐free treatments. RBV has been used in 70 patients (40.2%); 59 (33.9%) patients were in opioid substitution therapy (OST) with methadone or buprenorphine. Overall, sustained virological response (SVR) has been observed in 162 subject (93.1%), breakthrough (BT) in three (1.7%), relapse in one (0.6%) and dropout in eight (4.6%). Treatment was interrupted for clinical conditions in seven patients: six (3.4%) had hepatic decompensation and one died for hepatocellular carcinoma (HCC). In multivariate analysis, predictive factors of treatment failure were as follows: albumin level below 3 g/dL (OR=7.190; 95% IC=1.236‐41.837; P<.001), MELD score >10 (OR=5.886; 95% IC=1.411‐35.994; P<.001) and years of HCV infection >20 (OR=1.286; 95% IC=0.556‐9.455; P=.016). In conclusion, treatment with DAAs was effective and well tolerated in PWID; cirrhotic subjects with MELD > 10 and albumin low level showed a higher risk of developing serious adverse events and treatment failure.
Can genomic data alone tell us whether speciation happened with gene flow?
Authors: Yang Ming , He Ziwen , Shi Suhua , Wu Chung‐I
Published: March 2017

The allopatric model, which requires a period of geographical isolation for speciation to complete, has been the standard model in the modern era. Recently, “speciation with gene flow” has been widely discussed in relation to the model of “strict allopatry” and the level of DNA divergence across genomic regions. We wish to caution that genomic data by themselves may only permit the rejection of the simplest form of allopatry. Even a slightly more complex and realistic model that starts with subdivided populations would be impossible to reject by the genomic data alone. To resolve this central issue of speciation, other forms of observations such as the sequencing of reproductive isolation genes or the identification of geographical barrier(s) will be necessary.
Retention of gene diversity during the spread of a non‐native plant species
Authors: Vandepitte Katrien , Helsen Kenny , Van Acker Kasper , Mergeay Joachim , Honnay Olivier
Published: March 2017

Spatial expansion, which is a crucial stage in the process to successful biological invasion, is anticipated to profoundly affect the magnitude and spatial distribution of genetic diversity in novel colonized areas. Here, we show that, contrasting common expectations, Pyrenean rocket (Sisymbrium austriacum), retained SNP diversity as this introduced plant species descended in the Meuse River Basin. Allele frequencies did not mirror between‐population distances along the predominant expansion axis. Reconstruction of invasion history based on the genotypes of historical herbarium specimens indicated no influence of additional introductions or multiple points of entry on this nongradual pattern. Assignment analysis suggested the admixture of distant upstream sources in recently founded downstream populations. River dynamics seem to have facilitated occasional long‐distance dispersal which brought diversity to the expansion front and so maintained evolutionary potential. Our findings highlight the merit of a historical framework in interpreting extant patterns of genetic diversity in introduced species and underscore the need to integrate long‐distance dispersal events in theoretical work on the genetic consequences of range expansion.
Evidence for the generation of myristylated FMN by bacterial luciferase
Authors: Tabib Chaitanya R. , Brodl Eveline , Macheroux Peter
Published: March 2017

The genes responsible for the light production in bioluminescent bacteria are present as an operon, luxCDABEG. Many strains of Photobacteria carry an additional gene, termed luxF. X‐ray crystallographic analysis of LuxF revealed the presence of four molecules of a flavin derivative, i.e. 6‐(3′‐(R)‐myristyl) flavin adenine mononucleotide (myrFMN) non‐covalently bound to the homodimer. In the present study, we exploited the binding of myrFMN to recombinant apo‐LuxF to explore the occurrence of myrFMN in various bioluminescent bacteria. MyrFMN was detected in all bacterial strains tested including Vibrio and Aliivibrio indicating that it is more widely occurring in bioluminescent bacteria than previously assumed. We also show that apo‐LuxF captures myrFMN and thereby relieves the inhibitory effect on luciferase activity. Thus our results provide support for the hypothesis that LuxF acts as a scavenger of myrFMN in bioluminescent bacteria. However, the source of myrFMN remained obscure. To address this issue, we established a cofactor regeneration enzyme‐catalyzed cascade reaction that supports luciferase activity in vitro for up to 3 days. This approach enabled us to unambiguously demonstrate that myrFMN is generated in the bacterial bioluminescent reaction. Based on this finding we postulate a reaction mechanism for myrFMN generation that is based on the luciferase reaction.
A systematic review of genetic syndromes with obesity
Authors: Kaur Y. , de Souza R. J. , Gibson W. T. , Meyre D.
Published: March 2017

Syndromic monogenic obesity typically follows Mendelian patterns of inheritance and involves the co‐presentation of other characteristics, such as mental retardation, dysmorphic features and organ‐specific abnormalities. Previous reviews on obesity have reported 20 to 30 syndromes but no systematic review has yet been conducted on syndromic obesity. We searched seven databases using terms such as ‘obesity’, ‘syndrome’ and ‘gene’ to conduct a systematic review of literature on syndromic obesity. Our literature search identified 13,719 references. After abstract and full‐text review, 119 relevant papers were eligible, and 42 papers were identified through additional searches. Our analysis of these 161 papers found that 79 obesity syndromes have been reported in literature. Of the 79 syndromes, 19 have been fully genetically elucidated, 11 have been partially elucidated, 27 have been mapped to a chromosomal region and for the remaining 22, neither the gene(s) nor the chromosomal location(s) have yet been identified. Interestingly, 54.4% of the syndromes have not been assigned a name, whereas 13.9% have more than one name. We report on organizational inconsistencies (e.g. naming discrepancies and syndrome classification) and provide suggestions for improvements. Overall, this review illustrates the need for increased clinical and genetic research on syndromes with obesity.
Cytokine and antioxidant gene profiles from peripheral blood mononuclear cells of Pelibuey lambs after Haemonchus contortus infection
Authors: Estrada‐Reyes Z. , López‐Arellano M. E. , Torres‐Acosta F. , López‐Reyes A. , Lagunas‐Martínez A. , Mendoza‐de‐Gives P. , González‐Garduño R. , Olazarán‐Jenkins S. , Reyes‐Guerrero D. , Ramírez‐Vargas G.
Published: March 2017

The expression profiles of cytokines and antioxidant genes were determined from an experimental infection with H. contortus in Pelibuey lambs. The infection was followed for 34 days (d) to determine the number of eggs per gram (epg) and the packed cell volume (PCV). Differential white cell counts and expression profile estimations of IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐13, FCεR1A, GPX and SOD1 were determined at 0 hour, 4 hours, 2 days and 14 days post‐infection (PI) in infected and control groups. Comparison of the fold change between 0 and 4‐hours, 4‐hours and 2‐days and 2‐ and 14‐days periods was performed. Significant differences (P<.05) between epg (>2000) and PCV (>30%) were determined after 21 days and were also observed with regard to monocyte and lymphocyte cells after 2 and 7 days PI. At 0 hour and 14 days PI, the GPX and IL‐2 genes showed a 0.37‐ and 0.49‐fold decrease in expression, respectively. In contrast, upregulation was observed at 4 hours of IL‐8 (2.58) and FCεR1A (2.71), at 2 days for IL‐4 (2.14) and IL‐8 (4.02) and at 14 days for IL‐2 (0.41), IL‐10 (2.35) and FCεR1A (2.28). The comparison between the intervals of infection showed high expression values against H. contortus infection in Pelibuey sheep after the 2nd period of PI involving a dichotomy T cells.
Telerehabilitation for COPD: Could pulmonary rehabilitation deliver on its promise?
Authors: Holland Anne E. , Cox Narelle S.
Published: March 2017

See article, page 699
The Late Cretaceous Klepa basalts in Macedonia (FYROM)—Constraints on the final stage of Tethys closure in the Balkans
Authors: Prelević Dejan , Wehrheim Simon , Reutter Magnus , Romer Rolf L. , Boev Blažo , Božović Milica , van den Bogaard Paul , Cvetković Vladica , Schmid Stefan M.
Published: March 2017

The waning stage(s) of the Tethyan ocean(s) in the Balkans are not well understood. Controversy centres on the origin and life‐span of the Cretaceous Sava Zone, which is allegedly a remnant of the last oceanic domain in the Balkan Peninsula, defining the youngest suture between Eurasia‐ and Adria‐derived plates. In order to investigate to what extent Late‐Cretaceous volcanism within the Sava Zone is consistent with this model we present new age data together with trace‐element and Sr–Nd–Pb isotope data for the Klepa basaltic lavas from the central Balkan Peninsula. Our new geochemical data show marked differences between the Cretaceous Klepa basalts (Sava Zone) and the rocks of other volcanic sequences from the Jurassic ophiolites of the Balkans. The Klepa basalts mostly have Sr–Nd–Pb isotopic and trace‐element signatures that resemble enriched within‐plate basalts substantially different from Jurassic ophiolite basalts with MORB, BAB and IAV affinities. Trace‐element modelling of the Klepa rocks indicates 2%–20% polybaric melting of a relatively homogeneously metasomatised mantle source that ranges in composition from garnet lherzolite to ilmenite+apatite bearing spinel–amphibole lherzolite. Thus, the residual mineralogy is characteristic of a continental rather than oceanic lithospheric mantle source, suggesting an intracontinental within‐plate origin for the Klepa basalts. Two alternative geodynamic models are internally consistent with our new findings: (1) if the Sava Zone represents remnants of the youngest Neotethyan Ocean, magmatism along this zone would be situated within the forearc region and triggered by ridge subduction; (2) if the Sava Zone delimits a diffuse tectonic boundary between Adria and Europe which had already collided in the Late Jurassic, the Klepa basalts together with a number of other magmatic centres represent volcanism related to transtensional tectonics.