bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing safety information of biosimilars with their originators: a cross‐sectional analysis of European risk management plans
Authors: Lepelaars Leroy R. A. , Renda Francesca , Pani Luca , Pimpinella Giuseppe , Leufkens Hubert G. M. , Trifirò Gianluca , Tafuri Giovanni , Mantel‐Teeuwisse Aukje K. , Trotta Francesco
Published: November 2017

Background and aims

Biosimilars have been available in the European Union (EU) since 2006. However, their uptake in routine care is heterogeneous across countries. The aim of the present study was to compare the safety information of biosimilars and their originators based on the information in the European risk management plan (RMP).

Methods

A cross‐sectional analysis on publicly available regulatory documents (RMPs and Summaries of Product Characteristics) of biosimilars and corresponding originators up to 1 November 2015 was performed. The safety concerns were extracted and merged into general safety concerns, and clinical relevance was assessed. The frequency of safety concerns and the representation of these safety concerns per general safety concern were assessed by either comparing RMPs of biosimilars and originators (if available for both) or comparing RMPs with the Summary of Product Characteristics of the originator.

Results

Nineteen biosimilars and six originators were included. Overall, 55 general safety concerns (12 low, 21 medium and 22 highly clinically relevant) were identified. For all active substances, except for infliximab, no or only one difference was found in the listed general safety concerns. Comparison of regulatory documents for infliximab identified three medium clinically relevant general safety concerns more for infliximab biosimilars and two general safety concerns more for its originator.

Conclusion

Based on publicly available information filed for regulatory purposes, no substantial differences were observed in the reporting of safety information for biosimilars and related originators. A direct comparison between biosimilars and related originators through formal postmarketing studies is needed to evaluate specific safety issues emerging during the products’ life cycle.
Variation in the Response of Clozapine Biotransformation Pathways in Human Hepatic Microsomes to CYP1A2‐ and CYP3A4‐selective Inhibitors
Authors: Murray Michael , Zhang Wei V. , Edwards Robert J.
Published: November 2017

The atypical antipsychotic agent clozapine (CLZ) is effective in many patients who are resistant to conventional antipsychotic drugs. Cytochromes P450 (CYPs) 1A2 and 3A4 oxidize CLZ to norCLZ and CLZ N‐oxide in human liver. Concurrent treatment with inducers and inhibitors of CYP1A2 modulates CLZ elimination that disrupts therapy. Drug–drug interactions involving CYP3A4 are also significant but less predictable. To further characterize the factors underlying these interactions, we used samples from a cohort of human livers to assess variation in CLZ oxidation pathways in relation to intrinsic CYP3A4 and CYP1A2 activities and the effects of the corresponding selective inhibitors ketoconazole (0.2 and 2 μM) and fluvoxamine (1 and 10 μM). The CYP3A4‐selective inhibitor ketoconazole (2 μM) impaired CLZ N‐oxide formation in all 14 of the livers used in inhibition studies (≥50% inhibition) while the CYP1A2‐selective inhibitor fluvoxamine (10 μM) decreased norCLZ formation in nine. Ketoconazole effectively inhibited CLZ metabolism in five of seven livers that catalysed CYP3A4‐dependent testosterone 6β‐hydroxylation at or above the median rate and in four other livers with lower intrinsic CYP3A4 activity. Similarly, fluvoxamine (10 μM) readily inhibited CLZ oxidation in seven livers with high CYP1A2‐mediated 7‐ethoxyresorufin O‐deethylation activity (at or above the median) and three livers with lower intrinsic CYP1A2 activity. In three livers, CLZ biotransformation was impaired by both ketoconazole and fluvoxamine, consistent with a major role for both CYPs. These findings suggest that the intrinsic activities of CYPs 1A2 and 3A4 are unrelated to the response to CYP‐selective inhibitors and that assessment of the activities in vivo may not assist the prediction of drug–drug interactions.
Perceptions of the effects of childbirth on sexuality among nulliparous individuals
Authors: Cappell Jaclyn , Pukall Caroline F.
Published: November 2017

Background

Media representations of sexuality after childbirth depict vaginal birth as harmful and cesarean delivery as protective, although research does not support these depictions. The objective of the current study was to investigate perceptions of the effects of mode of delivery on sexuality.

Methods

Nulliparous participants who were able to and interested in giving birth (N = 1428) completed an online survey about their preferences for mode of delivery and their perceptions of childbirth as they specifically relate to sexuality. Participants provided demographic information, rated how influential different sources of information about childbirth were, and completed the Attitudes Toward Women's Genitals Scale.

Results

Up to half (16‐48%), the participants agreed with different statements about vaginal birth as harmful to, and cesarean delivery as protective of, future sexuality. Participant characteristics that were independently predictive of endorsing these beliefs were: self‐identifying as heterosexual, holding negative attitudes toward women's genitals, and reporting that reality media, nonreality media, and online media sources are influential sources of childbirth information. Participants who rated health care professionals as an influential source of information were less likely to endorse these beliefs.

Conclusion

Given that there is no clear evidence in the empirical literature to support the claim that vaginal births are harmful and cesarean delivery is protective to one's future sexual life, it is important to dispel the existing misconceptions. Various media sources likely play a role in the perpetuation of this misinformation.
Secondary suites, second‐class citizens: The history and geography of Calgary's most controversial housing policy
Authors: van der Poorten Kylee , Miller Byron
Published: November 2017

Key Messages

In Calgary, unauthorized secondary suites are geographically concentrated in specific immigrant and low‐income neighbourhoods.

The majority of secondary suites are operated by absentee landlords, challenging the narrative that multi‐generational housing among immigrants dominates the secondary suite market.

Unequal power relations among landlords, community associations, oppositional neighbours, and renters shapes secondary suite policy, potentially jeopardizing the health and safety of renters.
Double‐blind placebo‐controlled trial of the effect of omalizumab on basophils in chronic urticaria patients
Authors: Jörg L. , Pecaric‐Petkovic T. , Reichenbach S. , Coslovsky M. , Stalder O. , Pichler W. , Hausmann O.
Published: November 2017

Background

Omalizumab has been shown to be effective in treating chronic spontaneous urticaria (CSU). The reduction in FcεRI receptor density on the surface of basophils and mast cells is thought to play a major role in its effectiveness. We conducted a double‐blind, randomized, placebo‐controlled trial to investigate the mode of action of omalizumab in patients with antihistamine‐resistant CSU.

Methods

Thirty patients were randomized in a 2:1 ratio to receive either 300 mg omalizumab or placebo. Four monthly applications of omalizumab/placebo were followed up with a visit 2 months after the last injection. The primary endpoint was the FcεRI receptor density change on basophils.

Results

Omalizumab led to a significant reduction in FcεRI receptor density on basophils as soon as 1 week after the first injection: baseline omalizumab vs placebo group, 80.31 ± 47.18 × 10³ vs 78.29 ± 45.09 × 10³ receptors/basophil ± SD; 1 week, 72.89 ± 47.79 × 10³ vs 27.83 ± 20.87 × 10³, P = .001. This effect continued during the treatment phase and persisted for 2 months after the last injection: 93.81 ± 56.50 × 10³ vs 21.09 ± 15.23 × 10³, P = .002. Values for basophil “releasability” and the basophil activation test (CU‐BAT) of patient serum using donor basophils were unchanged despite treatment: CU‐BAT, CD63 10.75% (7.35) in the placebo group vs 8.35% (15.20) in the omalizumab group, P = .778.

Conclusion

We demonstrated a rapid reduction of FcεRI receptor density on basophils following treatment with omalizumab. Because CU‐BAT using well‐characterized, omalizumab‐naïve donor basophils did not change during the treatment phase, autoreactive serum factors seem to remain unaltered. This points towards a cellular effect of omalizumab on basophils. To predict the omalizumab response time and to monitor disease, FcεRI density and CU‐BAT might be promising cellular‐based assays.
Bayesian Word Learning in Multiple Language Environments
Authors: Zinszer Benjamin D. , Rolotti Sebi V. , Li Fan , Li Ping
Published: November 2017

Infant language learners are faced with the difficult inductive problem of determining how new words map to novel or known objects in their environment. Bayesian inference models have been successful at using the sparse information available in natural child‐directed speech to build candidate lexicons and infer speakers’ referential intentions. We begin by asking how a Bayesian model optimized for monolingual input (the Intentional Model; Frank et al., 2009) generalizes to new monolingual or bilingual corpora and find that, especially in the case of the bilingual input, the model shows a significant decrease in performance. In the next experiment, we propose the ME Model, a modified Bayesian model, which approximates infants’ mutual exclusivity bias to support the differential demands of monolingual and bilingual learning situations. The extended model is assessed using the same corpora of real child‐directed speech, showing that its performance is more robust against varying input and less dependent than the Intentional Model on optimization of its parsimony parameter. We argue that both monolingual and bilingual demands on word learning are important considerations for a computational model, as they can yield significantly different results than when only one such context is considered.
Rosettes in papillary carcinoma of thyroid: A rare cytomorphological indicator of aggressive variants
Authors: Nambirajan A. , Batool S. , Mandal P. , Nakra T. , Agarwal S. , Jain D.
Published: November 2017

We present a case of tall cell variant of papillary carcinoma of thyroid diagnosed on cytology showing predominance of rosette‐like formations. Also described previously for the columnar cell variant, these rosettes need to be differentiated from micro‐follicles and are an indicator for aggressive variants.
Changes in alcohol policies and practices in bars and restaurants after completion of manager‐focused responsible service training
Authors: Lenk Kathleen M. , Erickson Darin J. , Nelson Toben F. , Horvath Keith J. , Nederhoff Dawn M. , Hunt Shanda L. , Ecklund Alexandra M. , Toomey Traci L.
Published: November 2017

Introduction and Aims

Irresponsible and illegal serving practices at bars and restaurants, such as sales to obviously intoxicated patrons, can lead to various public health harms. Training managers of bars and restaurants in the development and promotion of responsible alcohol policies may help prevent risky and illegal alcohol serving practices.

Design and Methods

We implemented a training program for managers of bars/restaurants designed to establish and promote responsible beverage service policies/practices. The program included online and in‐person components. Bars/restaurants were randomised to intervention (n = 171) and control (n = 163) groups. To assess changes in policies/practices, we surveyed managers prior to and at 1 and 6 months post‐training. Logistic regression models assessed changes in policies/practices across time points.

Results

The proportion in the intervention group that had written alcohol policies increased from 62% to 95% by 6 months post‐training while the control group increased from 65% to 79% (P < 0.05). Similarly, by 6 months post‐training 70% of managers in the intervention group reported they had communicated to their staff how to cut off intoxicated patrons, a significant increase from baseline (37%) and from the change observed in the control group (43%–56%). Prevalence of other policies/practices also increased post‐training but differences between intervention and control groups were not statistically significant.

Discussion and Conclusions

Our training program appears to have led to implementation of some policies/practices. Additional studies are needed to determine how training can be combined with other strategies to further improve establishment policies and ultimately reduce alcohol‐related harms.
Novel technique using a non‐tip and short‐wire papillotome for biliary cannulation of intradiverticular papilla in patients with Roux‐en‐Y anastomosis
Authors: Suguro Maya , Yamamoto Kenjiro , Itoi Takao
Published: November 2017

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Ecological selection of siderophore‐producing microbial taxa in response to heavy metal contamination
Authors: Hesse Elze , O'Brien Siobhán , Tromas Nicolas , Bayer Florian , Luján Adela M. , van Veen Eleanor M. , Hodgson Dave J. , Buckling Angus
Published: November 2017

Some microbial public goods can provide both individual and community‐wide benefits, and are open to exploitation by non‐producing species. One such example is the production of metal‐detoxifying siderophores. Here, we investigate whether conflicting selection pressures on siderophore production by heavy metals – a detoxifying effect of siderophores, and exploitation of this detoxifying effect – result in a net increase or decrease. We show that the proportion of siderophore‐producing taxa increases along a natural heavy metal gradient. A causal link between metal contamination and siderophore production was subsequently demonstrated in a microcosm experiment in compost, in which we observed changes in community composition towards taxa that produce relatively more siderophores following copper contamination. We confirmed the selective benefit of siderophores by showing that taxa producing large amounts of siderophore suffered less growth inhibition in toxic copper. Our results suggest that ecological selection will favour siderophore‐mediated decontamination, with important consequences for potential remediation strategies.
Interleukin‐17 alters the biology of many cell types involved in the genesis of psoriasis, systemic inflammation and associated comorbidities
Authors: Krueger James G. , Brunner Patrick M.
Published: November 2017

Psoriasis is a chronic, immune‐mediated, systemic inflammatory disease that is defined by a characteristic skin reaction produced when elevated levels of inflammatory cytokines such as interleukin (IL)‐17 alter the growth and differentiation of skin cells. The pathogenesis of comorbid conditions associated with psoriasis, including psoriatic arthritis, cardiovascular disease, obesity, metabolic syndrome, liver disorders, renal disease and depression, is also largely affected by inflammation. In this review, we examine the effect of IL‐17 on the inflammatory pathways in a variety of different cell types, including keratinocytes, as well as epithelial cells of the colon, kidney, gut and liver. Additionally, we investigate the role of IL‐17 in mediating the psoriasis‐associated comorbidities detailed above.
PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP‐1
Authors: Kumar Vikash , Kaur Jasweer , Singh Amrit P. , Singh Vineeta , Bisht Anjali , Panda Jiban J. , Mishra Prakash C. , Hora Rachna
Published: November 2017

Plasmodium falciparum encodes a novel repertoire of the Plasmodium helical interspersed subtelomeric (PHIST) family of exported proteins, which play diverse roles in infected red blood cells, contributing to malaria pathogenesis. PHIST proteins are central to parasite biology and modify human erythrocytes by interacting with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of the PHISTc subfamily, PFD1140w and PF11_0503, and compared these with a well‐characterized member, PFI1780w. We demonstrate that Phist domains assume different oligomeric states owing to a distinct array of subunit interface residues. Colocalization of a Maurer's cleft signature protein, P. falciparum skeleton‐binding protein‐1 (PfSBP‐1), and P. falciparum erythrocyte membrane protein‐1 (PfEMP‐1) revealed different subcellular destinations for these PHIST members. We further show the binding of recombinant PHIST proteins to the cytoplasmic tail of PfEMP‐1 and a novel interaction with PfSBP‐1. Interestingly, PFD1140w interacts with PfEMP‐1 and PfSBP‐1 simultaneously in vitro leading to formation of a complex. These two distant PHISTc members also bind PfEMP‐1 on distinct sites, despite sharing the Phist domain. Our data re‐emphasize a supportive role for PHIST proteins in cytoadhesion, and identify a new binding partner, PfSBP‐1, for members of this family. This information therefore adds another chapter to the understanding of P. falciparum biology and highlights the significance of the unexplored PHIST family.
The sensitivity of breeding songbirds to changes in seasonal timing is linked to population change but cannot be directly attributed to the effects of trophic asynchrony on productivity
Authors: Franks Samantha E. , Pearce‐Higgins James W. , Atkinson Sian , Bell James R. , Botham Marc S. , Brereton Tom M. , Harrington Richard , Leech David I.
Published: November 2017

A consequence of climate change has been an advance in the timing of seasonal events. Differences in the rate of advance between trophic levels may result in predators becoming mismatched with prey availability, reducing fitness and potentially driving population declines. Such “trophic asynchrony” is hypothesized to have contributed to recent population declines of long‐distance migratory birds in particular. Using spatially extensive survey data from 1983 to 2010 to estimate variation in spring phenology from 280 plant and insect species and the egg‐laying phenology of 21 British songbird species, we explored the effects of trophic asynchrony on avian population trends and potential underlying demographic mechanisms. Species which advanced their laying dates least over the last three decades, and were therefore at greatest risk of asynchrony, exhibited the most negative population trends. We expressed asynchrony as the annual variation in bird phenology relative to spring phenology, and related asynchrony to annual avian productivity. In warmer springs, birds were more asynchronous, but productivity was only marginally reduced; long‐distance migrants, short‐distance migrants and resident bird species all exhibited effects of similar magnitude. Long‐term population, but not productivity, declines were greatest among those species whose annual productivity was most greatly reduced by asynchrony. This suggests that population change is not mechanistically driven by the negative effects of asynchrony on productivity. The apparent effects of asynchrony on population trends are therefore either more likely to be strongly expressed via other demographic pathways, or alternatively, are a surrogate for species' sensitivity to other environmental pressures which are the ultimate cause of decline.
Paintings predict the distribution of species, or the challenge of selecting environmental predictors and evaluation statistics
Authors: Fourcade Yoan , Besnard Aurélien G. , Secondi Jean
Published: November 2017

Aim

Species distribution modelling, a family of statistical methods that predicts species distributions from a set of occurrences and environmental predictors, is now routinely applied in many macroecological studies. However, the reliability of evaluation metrics usually employed to validate these models remains questioned. Moreover, the emergence of online databases of environmental variables with global coverage, especially climatic, has favoured the use of the same set of standard predictors. Unfortunately, the selection of variables is too rarely based on a careful examination of the species' ecology. In this context, our aim was to highlight the importance of selecting ad hoc variables in species distribution models, and to assess the ability of classical evaluation statistics to identify models with no biological realism.

Innovation

First, we reviewed the current practices in the field of species distribution modelling in terms of variable selection and model evaluation. Then, we computed distribution models of 509 European species using pseudo‐predictors derived from paintings or using a real set of climatic and topographic predictors. We calculated model performance based on the area under the receiver operating curve (AUC) and true skill statistics (TSS), partitioning occurrences into training and test data with different levels of spatial independence. Most models computed from pseudo‐predictors were classified as good and sometimes were even better evaluated than models computed using real environmental variables. However, on average they were better discriminated when the partitioning of occurrences allowed testing for model transferability.

Main conclusions

These findings confirm the crucial importance of variable selection and the inability of current evaluation metrics to assess the biological significance of distribution models. We recommend that researchers carefully select variables according to the species' ecology and evaluate models only according to their capacity to be transfered in distant areas. Nevertheless, statistics of model evaluations must still be interpreted with great caution.
Spontaneous perirenal hemorrhage in hemodialysis patient treated with selective embolization: A case series and review of the literature
Authors: Xie Yun , Yang Bo , Jiang Gengru , Lu Wei , Ronco Claudio
Published: November 2017

Introduction: Spontaneous perirenal hemorrhage (SPH) or Wunderlich syndrome, is a rare but potentially life‐threatening condition. It is characterized by an unexpected bleeding in the kidneys and usually presents as an abdominal pain. Angiography and more recently selective renal arterial embolization are emerging as effective modalities for the diagnosis and treatment of SPH. In this article, we report a total of three cases of SPH in hemodialysis (HD) patients.

Methods: This is the experience of diagnosis and treatment of SPH in HD patients.

Findings: All three were female, between 37 and 54 years of age and were undergoing HD for end stage renal disease (ESRD). Two of patients presented with left flank or abdominal pain after termination of HD therapy, while the third patient presented with left abdominal pain during the dialysis session. All patients received anti‐coagulation therapy for HD, but no abnormal levels of coagulation index were found. These patients were diagnosed using CT and two of them were diagnosed with acquired cystic kidney disease (ACKD). Selective renal arterial embolization was performed in the case of active bleeding.

Discussion: We are aware that HD patients have elevated risk of bleeding related complications, additionally the presence of an acute abdominal pain increases the suspicion of SPH as a possible cause. ACKD can be considered one of the possible risk factors for SPH in long‐term HD patients. Interventional treatment for kidney injury is useful and safe for active bleeding in most cases.
Diabetes‐related complications: Which research topics matter to diverse patients and caregivers?
Authors: Dogba Maman Joyce , Dipankui Mylène Tantchou , Chipenda Dansokho Selma , Légaré France , Witteman Holly O.
Published: November 2017

Background

Diabetes is a chronic disease with increasing prevalence worldwide. Although research has improved its treatment and management, little is known about which research topics matter to people living with diabetes, particularly among under‐represented groups.

Objectives

To explore the importance of research topics among a diverse range of people living with any type of diabetes or caring for someone living with any type of diabetes.

Methods

We used a convergent mixed‐method design with quantitative and qualitative aspects. We surveyed a national sample of people living with diabetes and caregivers of people with diabetes, asking them to rate the importance of 10 predetermined important research topics. We also held three focus groups in two major cities to explore research concerns of people who are under‐represented in research.

Results

469 adults (57% men, 42% women) in Canada completed the online survey, indicating that all 10 areas of research mattered to them, with the highest ratings accorded to preventing and treating kidney, eye and nerve complications. Fourteen individuals participated in three focus groups and similarly noted the importance of research on those three complications. Additionally, focus group participants also noted the importance of research around daily management. No new topics were identified.

Conclusions

This study confirmed the importance of research topics among a population of people living with or caring for someone with diabetes. Findings from this study were used to inform the vision for Diabetes Action Canada—a pan‐Canadian Strategy for Patient‐Oriented Research (SPOR) Network on diabetes and its complications.
Budget over health unless overweight: A Solomon four‐group study
Authors: Yin Yue , Özdinç Yalım
Published: November 2017

Budget and health motivations for food purchase (e.g., discounts and health consciousness, respectively) affect consumer choice while shopping and well‐being afterward. However, not all findings from research have suggested that discounts/taxations on healthy/unhealthy food encourage health‐conscious food choice. On the other hand, the consumer behaviour line of research on the influence of front‐of‐package health messages has mostly echoed similar results that such communication leads to overconsumption; thus, obesity. We examined the influence of market practices targeting consumers’ budget and health‐related motivations for food purchase in a 2 (price: recommended retail price, discount price) × 2 (product: regular potato chips, potato chips with ‘75% less saturated fat’) experiment using six Solomon four‐group designs. Our results indicate that overweight consumers are not prone to discounts, unlike their normal‐weight counterparts. A price cut nullifies the influence of health messages on purchase intentions among normal‐weight buyers when the regular and healthier packaged foods are both on discount.
Autoantibodies to full body vascular cell junctions colocalize with MYZAP, ARVCF, desmoplakins I and II and p0071 in endemic pemphigus in Colombia, South America
Authors: Abreu Velez Ana M. , Yi Hong , Warfvinge Gunnar , Howard Michael S.
Published: November 2017

Background

We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre‐EPF).

Methods

Here we aimed to investigate disease autoreactivity to vessels in all body organs/systems. We compared 57 patients and 57 controls from the endemic area, matched by demographics, age, sex, and work activity. We performed immunofluorescence, immunohistochemistry, confocal microscopy, immunoblotting, indirect immune electron microscopy studies, and autometallographic studies. We performed ultrasonography on large patient arteries, investigating for vascular anomalies. In addition, we reviewed autopsies on seven patients who died affected by El Bagre‐EPF. We immunoadsorbed any positive vessel immunofluorescence with desmoglein (Dsg1), investigating for new autoantigens.

Results

Overall, 57/57 patients affected by El Bagre‐EPF displayed autoantibodies to vessels in all the organs/systems of the body via all methods (P < 0.01). The autoreactivity was polyclonal, and the patient's antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, ARVCF, and MYZAP (all from Progen Biotechnik, Germany; P < 0.01; all present at cell junctions). Immunoadsorption with Dsg1 on positive vessel immunofluorescence showed that the immune response against the vessels was directed against non‐Dsg1 antigen(s). Autometallographic studies showed deposits of metals and metalloids in vessel cell junctions and in erythrocytes of 85% of patients (P < 0.01).

Conclusions

Immune response to these vascular antigens is likely altering endothelial cells and vessel shapes, thus disturbing hemodynamic flow. The flow alterations likely lead to inflammation and may play a role in the atherogenesis often seen in these patients.
Training therapists to work with people with intellectual disability in Improving Access to Psychological Therapies (IAPT) services
Authors: Dagnan Dave , Masson John , Thwaites Richard , James Amy , Hatton Chris
Published: November 2017

Background

Current policy in the England suggests that people with intellectual disabilities should, where possible, access mainstream mental health services; this should include access to mainstream therapy services. It is likely that mainstream therapists will need training and support to work with people with intellectual disabilities.

Method

Sixty‐eight therapists working in an English Improving Access to Psychological Therapies (IAPT) service received one‐ or 2‐day training on working with people with intellectual disabilities. Measures of confidence, general therapeutic self‐efficacy and attitudes to people with intellectual disabilities’ use of mainstream mental health services were completed pre‐training, post‐training and at 3‐month follow‐up; at which time, 12 participants were interviewed about the impact of the training on their practice.

Results

There was a significant positive change in all measures immediately post‐training which was maintained at 3‐month follow‐up.

Conclusions

Training considerations for mainstream therapists who may work with people with intellectual disabilities are discussed.
Lower gastrointestinal bleeding in patients with coronary artery disease on antithrombotics and subsequent mortality risk
Authors: Patel Parita , Nigam Neha , Sengupta Neil
Published: November 2017

Background

Lower gastrointestinal bleeding (LGIB) is a common complication for patients with coronary artery disease (CAD) due to the use of antithrombotic medications. Limited data exist describing which patients are at increased risk for mortality.

Aim

This study aims to (i) determine whether patients on dual antiplatelet therapy (DAPT) or triple therapy are at higher risk of 90‐day and 6‐month mortality compared with patients on aspirin alone and (ii) evaluate risk factors for mortality in patients with CAD on antithrombotics hospitalized with LGIB.

Methods

We conducted a retrospective cohort study of patients hospitalized with LGIB and CAD while on aspirin at a single academic medical center from 2007 to 2015. Patients were identified using a validated, machine‐learning algorithm and classified by use of aspirin, DAPT, or triple therapy. Univariate and multivariate Cox proportional hazards were used to determine mortality associated risk factors.

Results

Seven hundred sixteen patients were identified with LGIB and CAD. Four hundred seventy‐two (65.9%) patients were on aspirin monotherapy, 179 (25%) on aspirin and thienopyridine (DAPT), and 65 (9.1%) on aspirin, thienopyridine, and systemic anticoagulant (triple therapy). On univariate analysis, triple therapy use was associated with increased risk of 90‐day (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.52–5.92,P = 0.003) and 6‐month (HR 2.46, 95%CI 1.29–4.35,P = 0.008) mortality. Holding anticoagulation was associated with higher mortality at 90 days (HR 2.30, 95%CI 1.27–4.07,P = 0.007). On multivariate analysis, after adjusting for confounding variables, the use of triple therapy remained associated with higher 90‐day mortality (HR 3.23, 95%CI 1.56–6.16,P = 0.003).

Conclusion

Triple therapy is associated with mortality at 90 days and at 6 months post discharge.
Medicaid Cost Savings of a Preventive Home Visit Program for Disabled Older Adults
Authors: Szanton Sarah L. , Alfonso Y. Natalia , Leff Bruce , Guralnik Jack , Wolff Jennifer L. , Stockwell Ian , Gitlin Laura N. , Bishai David
Published: November 2017

Background/Objectives

Little is known about cost savings of programs that reduce disability in older adults. The objective was to determine whether the Community Aging in Place, Advancing Better Living for Elders (CAPABLE) program saves Medicaid more money than it costs to provide.

Design

Single‐arm clinical trial (N = 204) with a comparison group of individuals (N = 2,013) dually eligible for Medicaid and Medicare matched on baseline geographic and demographic characteristics, chronic conditions, and healthcare use. We used finite mixture model regression estimates in a Markov model.

Setting

Baltimore, MD

Participants

Individuals aged 65 and older with reported difficulty with at least one activity of daily living.

Intervention

CAPABLE is a 5‐month program to reduce the health effects of impaired physical function in low‐income older adults by addressing individual capacity and the home environment. CAPABLE uses an interprofessional team (occupational therapist, registered nurse, handyman) to help older adults attain self‐identified functional goals.

Measurements

Monthly average Medicaid expenditure and likelihood of high‐ or low‐cost use of eight healthcare service categories.

Results

Average Medicaid spending per CAPABLE participant was $867 less per month than that of their matched comparison counterparts (observation period average 17 months, range 1–31 months). The largest differential reduction in expenditures were for inpatient care and long‐term services and supports.

Conclusion

CAPABLE is associated with lower likelihood of inpatient and long‐term service use and lower overall Medicaid spending. The magnitude of reduced Medicaid spending could pay for CAPABLE delivery and provide further Medicaid program savings due to averted services use.

Clinical trial registration

CAPABLE for Frail dually eligible older adults NCT01743495 https://clinicaltrials.gov/ct2/show/NCT01743495
Targeting Function at Home in Older Adults: How to Promote and Disseminate Promising Models of Care?
Authors: Fortinsky Richard H. , Robison Julie T.
Published: November 2017

This editorial comments on the article by Szanton et al.
Building trophic specializations that result in substantial niche partitioning within a young adaptive radiation
Authors: Hernandez Luz Patricia , Adriaens Dominique , Martin Christopher H. , Wainwright Peter C. , Masschaele Bert , Dierick Manuel
Published: November 2017

Dietary partitioning often accompanies the increased morphological diversity seen during adaptive radiations within aquatic systems. While such niche partitioning would be expected in older radiations, it is unclear how significant morphological divergence occurs within a shorter time period. Here we show how differential growth in key elements of the feeding mechanism can bring about pronounced functional differences among closely related species. An incredibly young adaptive radiation of threeCyprinodonspecies residing within hypersaline lakes in San Salvador Island, Bahamas, has recently been described. Characterized by distinct head shapes, gut content analyses revealed three discrete feeding modes in these species: basal detritivory as well as derived durophagy and lepidophagy (scale‐feeding). We dissected, cleared and stained, and micro‐CT scanned species to assess functionally relevant differences in craniofacial musculoskeletal elements. The widespread feeding mode previously described for cyprinodontiforms, in which the force of the bite may be secondary to the requisite dexterity needed to pick at food items, is modified within both the scale specialist and the durophagous species. While the scale specialist has greatly emphasized maxillary retraction, using it to overcome the poor mechanical advantage associated with scale‐eating, the durophage has instead stabilized the maxilla. In all species the bulk of the adductor musculature is composed of AM A1. However, the combined masses of both adductor mandibulae (AM) A1 and A3 in the scale specialist were five times that of the other species, showing the importance of growth in functional divergence. The scale specialist combines plesiomorphic jaw mechanisms with both a hypertrophied AM A1 and a slightly modified maxillary anatomy (with substantial functional implications) to generate a bite that is both strong and allows a wide range of motion in the upper jaw, two attributes that normally tradeoff mechanically. Thus, a significant feeding innovation (scale‐eating, rarely seen in fishes) may evolve based largely on allometric changes in ancestral structures. Alternatively, the durophage shows reduced growth with foreshortened jaws that are stabilized by an immobile maxilla. Overall, scale specialists showed the most divergent morphology, suggesting that selection for scale‐biting might be stronger or act on a greater number of traits than selection for either detritivory or durophagy. The scale specialist has colonized an adaptive peak that few lineages have climbed. Thus, heterochronic changes in growth can quickly produce functionally relevant change among closely related species.
Open‐label study assessing the efficacy and tolerability of topical skincare and sun protection products following intense pulsed light treatment
Authors: Jones Isabela T , Guiha Isabella , Fabi Sabrina G
Published: November 2017

Background

The visible signs of photodamage can be improved by intense pulsed light (IPL). Active ingredients in cosmeceuticals also have effects on skin quality and pigmentation, and can camouflage post‐treatment side effects. Combination therapies utilizing different treatment modalities have been shown to optimize clinical outcomes for skin rejuvenation and patient satisfaction.

Aim

To evaluate the efficacy of a combination of IPL with a daily topical skincare and sunscreen regimen for the treatment of facial photodamage and for the improvement of IPL treatment tolerability.

Patients/Methods

Twenty female subjects with moderate‐to‐severe facial photodamage, with past history of IPL treatments, received one IPL treatment followed by the use of the topical skincare regimen for 8 weeks. An investigator assessed facial photodamage and hyperpigmentation at baseline, week 4, and week 8, and postprocedure erythema. Subject questionnaires were also administered at each visit.

Results

Compared to baseline, there was a significant improvement in photodamage and hyperpigmentation of bare facial skin. The application of the skincare regimen resulted in a significant reduction in post‐IPL erythema, stinging/burning, and itching. The majority of patients were very satisfied or satisfied and felt the treatment regimen improved various aspects of skin quality and the tolerability of the procedure.

Conclusions

The addition of a topical skincare regimen after IPL treatment to the face resulted in significant improvements in facial photodamage and pigmentation, decreased post‐treatment side effects, and increased tolerability.
Fundamental nursing care: A systematic review of the evidence on the effect of nursing care interventions for nutrition, elimination, mobility and hygiene
Authors: Richards David A. , Hilli Angelique , Pentecost Claire , Goodwin Victoria A. , Frost Julia
Published: November 2017

Aims and objectives

To determine the effects of nursing interventions for people's nutrition, elimination, mobility and hygiene needs.

Background

Patient experience of health care is sensitive to nursing quality. A refocus on fundamental nursing care is undermined by lack of evidence of effectiveness for interventions in core areas such as elimination, nutrition, mobility and hygiene.

Design

Systematic review.

Methods

We searched for and included experimental studies on interventions by professionally qualified and unregistered nurses that addressed participants' nutrition, elimination, mobility and hygiene needs. We extracted data on scope, quality and results of studies followed by descriptive narrative synthesis of included study outcomes using a novel form of harvest plots.

Results

We included 149 studies, 35 nutrition, 56 elimination, 16 mobility, 39 hygiene and three addressing two or more areas simultaneously (67 randomised controlled trials, 32 non‐randomised controlled trials and 50 uncontrolled trials). Studies into interventions on participant self‐management of nutrition (n = 25), oral health (n = 26), catheter care (n = 23) and self‐management of elimination (n = 21) were the most prevalent. Most studies focussed their outcomes on observational or physiological measures, with very few collecting patient‐reported outcomes, such as quality of life, experience or self‐reported symptoms. All but 13 studies were of low quality and at significant risk of bias. The majority of studies did not define primary outcomes, included multiple measures of identical concepts, used inappropriate analyses and did not conform to standard reporting quality criteria.

Conclusions

The current evidence for fundamental nursing care interventions is sparse, of poor quality and unfit to provide evidence‐based guidance to practising nurses.

Relevance to clinical practice

Researchers in nursing internationally should now undertake a programme of work to produce evidence for clinical practice in the fundamentals of care that is reliable, replicable and robust.
Expression of tomato reference genes using established primer sets: Stability across experimental set‐ups
Authors: Rezzonico Fabio , Nicot Philippe C. , Fahrentrapp Johannes
Published: November 2017

Reliable reference genes are critical for relative quantification using quantitative real‐time PCR (qPCR). Ten tomato genes (Solanum lycopersicum) and their respective primer sets, which have been used over the last 6 years as references in expression studies, were evaluated for their performance using leaf tissue samples grown under semi‐controlled conditions and infected with grey mould (Botrytis cinerea) or late blight (Phytophthora infestans). The target genes coding for U6 snRNA‐associated Sm‐like protein LSm7, calcineurin B‐like protein and V‐type proton ATPase were the most stable expressed of all the genes tested in three experimental repetitions. Evaluation of candidate reference genes with geNorm and NormFinder softwares yielded the lowest mean values for their respective primer sets LSM7, SlCBL1 and SlATPase, suggesting stable expression. However, SlATPase primer set revealed a comparably high intra‐group variation and was thus not considered further. In follow‐up experiments with P. infestans, the geNorm and NormFinder values of primer sets LSM7 and SlCBL1 were even lower, indicating the stability of their expression also under these conditions. Primer efficiency differed by ‐18 to +5 percentage points from values presented in the literature. Our findings show that a reference primer set which delivers the best results in one system may be outperformed by another under different experimental conditions, thus recommending a reassessment of both expression stability and qPCR efficiency whenever the biological or technical experimental set‐up is changed. On the basis of our results, we recommend the use of LSM7 and SlCBL1 as reference primer sets for gene expression studies on plant tissue derived from open or semi‐controlled conditions.
Circadian variation of flexor withdrawal and crossed extensor reflexes in patients with restless legs syndrome
Authors: Dafkin Chloe , Green Andrew , Olivier Benita , Mckinon Warrick , Kerr Samantha
Published: November 2017

An evening state of spinal hyperexcitability has been proposed to be a possible cause of evening increases in restless legs syndrome symptoms. Thus, the objective of the current study was to assess the circadian variation in spinal excitability in patients with restless legs syndrome based on flexor withdrawal reflex and crossed extensor reflex responses. The reflexes were elicited on 12 participants with restless legs syndrome and 12 healthy control participants in the evening (PM) and the morning (AM). Reflex response magnitudes were measured electromyographically and kinematically. Both the reflexes showed a circadian rhythm in participants with restless legs syndrome but not in control participants. Changes in ankle (median flexor withdrawal reflex PM: 16.0 ° versus AM: 2.8 °, P = 0.042; crossed extensor reflex PM: 0.8 ° versus AM: 0.2 °, P = 0.001) angle were significantly larger, and ankle angular velocity (median flexor withdrawal reflex PM: 38.8 ° s−1 versus AM: 13.9 ° s−1, P = 0.049; crossed extensor reflex PM: 2.4 ° s−1 versus AM: 0.5 ° s−1, P = 0.002) was significantly faster in the evening compared with the morning in participants with restless legs syndrome, for both reflexes. For participants with restless legs syndrome, evening change in hallux angle was significantly larger than morning responses (median PM: 5.0 ° versus AM: 1.3 °, P = 0.012). No significant differences for any of the electromyographic or kinematic variables were observed between participants with restless legs syndrome and controls. The flexor withdrawal reflex and the crossed extensor reflex show a circadian rhythm in participants with restless legs syndrome suggesting an evening increase in spinal excitability. We hypothesize the circadian variation in spinal excitability may be due to a possible nocturnal form of afferent circuitry central sensitization in the dorsal horn of the spinal cord in patients with restless legs syndrome.
Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection: The C‐SCAPE study
Authors: Brown A. , Hézode C. , Zuckerman E. , Foster G. R. , Zekry A. , Roberts S. K. , Lahser F. , Durkan C. , Badshah C. , Zhang B. , Robertson M. , Wahl J. , Barr E. , Haber B. ,   the C‐SCAPE Study Investigators
Published: November 2017

People with hepatitis C virus (HCV) infection other than genotype 1 represent a heterogeneous group. The aim of the phase 2 C‐SCAPE study was to evaluate elbasvir/grazoprevir (EBR/GZR), with or without ribavirin (RBV), in participants with HCV genotype 2, 4, 5 or 6 infection. This was a part randomised, open‐label, parallel‐group study (NCT01932762; PN047‐03) of treatment‐naive, noncirrhotic participants. Participants with HCV genotype 2 infection received GZR 100 mg + RBV ± EBR 50 mg for 12 weeks and those with genotype 4, 5 or 6 infection were randomized to receive EBR/GZR ± RBV for 12 weeks. The primary endpoint was sustained virological response 12 weeks after completion of treatment (SVR12; HCV RNA <25 IU/mL). Among participants with genotype 2 infection, SVR12 was achieved by 80% (24/30) of those receiving EBR/GZR + RBV and 73% (19/26) of those receiving GZR + RBV. SVR rates were high in participants with HCV genotype 4 infection receiving EBR/GZR with and without RBV (100% [10/10] and 90% [9/10]; respectively). In contrast, the addition of RBV to EBR/GZR appeared to increase SVR12 in participants with genotype 5 infection (EBR/GZR, 25%; EBR/GZR + RBV 100% [4/4]). In participants with genotype 6 infection, SVR12 was 75% (3/4) in both those receiving EBR/GZR and those receiving EBR/GZR + RBV. The safety profile was similar across treatment arms, with adverse events tending to occur more frequently among participants receiving RBV. In conclusion, these data support the inclusion of participants with genotype 4 or 6 infection in the EBR/GZR phase 3 studies. EBR/GZR ± RBV was unsatisfactory for participants with genotype 2 or 5 infection.