bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipid‐lowering therapy with PCSK9‐inhibitors in the real‐world setting: Two‐year experience of a regional lipid clinic
Authors: Zafrir Barak , Jubran Ayman
Published: June 2018

Aim

PCSK9 inhibitors (PCSK9i) effectively lower cholesterol levels in randomized trials with reduction in cardiovascular outcomes and favorable safety profile. However, the access to PCSK9i is limited due to high cost and data regarding the use of PCSK9i in real‐world practice is limited.

Methods

Data on all patients submitted for approval of PCSK9i at a regional lipid clinic, outside of clinical trials. Patients' profile, approval rates, low‐density lipoprotein cholesterol (LDL‐C) reduction rates, and adverse events were evaluated.

Results

Recommendation for PCSK9i was given to 133 patients; 16 did not receive insurance approval and additional 16 were approved but did not initiate therapy. Of the 101 treated patients (47% females; mean age 61 ± 11 years), 52 had probable/definite familial hypercholesterolemia (FH) (peak LDL‐C level 305 ± 87 mg/dL vs non‐FH 204 ± 39 mg/dL) and 62% had an established cardiovascular disease. Statin intolerance was reported by 77%. Follow‐up lipid panel was available in 66/101 patients: mean LDL‐C reduction was 59% ± 19. Subjects with heterozygous FH had similar LDL‐C decrease than those with non‐FH (59% ± 22 vs 60% ± 14, P = .792). LDL‐C < 100 mg/dL was achieved by 76%, LDL‐C < 70 mg/dL by 58% and LDL‐C < 40 mg/dL by 18% of those with follow‐up data. Side effects were reported by 10%, mainly musculoskeletal complaints and flu‐like symptoms, and 15% have discontinued treatment.

Conclusions

Patient selection by a regional lipid clinic resulted in a high real‐world PCSK9i insurance approval, with efficacy and safety comparable to randomized clinical trials. Cost and medication nonadherence are potential barriers to successful implementation of therapy in routine clinical care.
Extracts and phenolic compounds from Zuccagnia punctata as fungicide seed protectants for corn
Authors: Jiménez C. M. , Sgariglia M.A. , Soberón J.R. , Vattuone M.A. , Sampietro D.A.
Published: June 2018

The ethanolic leaf extract (TZP) of Zuccagnia punctata, its ethereal fraction (Eet), 2′,4′‐dihydroxychalcone (DC), 2′,4′‐dihydroxy‐3′‐methoxychalcone (DMC) and 7‐hydroxy‐3′,4′‐dimethoxyflavone (HF) were evaluated as fungicide seed protectants on corn. Microdilution assays on a set of Fusarium strains showed minimum inhibitory concentrations (MICs) of 400–800 μg mL−1 (TZP), 50–100 μg mL−1 (Eet), 25–50 μg mL−1 (DC), 50–100 μg mL−1 (DMC) and 200–400 μg mL−1 (HF), with minimum fungicidal concentration (MFC)/MIC = 1. Suspensions of TZP, Eet, DC and DMC at MIC × 20 incorporated to the grains at rates of 1920, 240, 120 and 240 mg dry matter kg−1 of grain, respectively, increased the elongation of the primary roots (24–44%) and the number of seminal roots (44–50%). TZP also increased the number of secondary roots. HF was phytotoxic. Suspensions of TZP, Eet, DC and DMC suppressed the endogenous grain mycoflora at levels similar to those recorded for a thiram + carbendazim‐based fungicide. Grains treated with TZP (1920 mg kg−1), Eet (240 mg kg−1), DC (120 mg kg−1) and DMC (240 mg kg−1) stimulated the growth of the seedling root system both because of fungal suppression and hormetic effects in greenhouse curative and preventive assays against Fusarium verticillioides on a sand/soil substrate. Eet and its chalcones also reduced the severity of seedling blight more than the thiram + carbendazim‐based fungicide in preventive assays and led to the same disease severity observed for the fungicide treatment in the curative assays. Our results show that Eet and its chalcones not only were effective seed protectants against F. verticillioides and other seedborne fungi, but also improved the early performance of maize seedlings.
Characteristics of depressive and bipolar disorder patients with mixed features
Authors: Tondo L. , Vázquez G. H. , Pinna M. , Vaccotto P. A. , Baldessarini R. J.
Published: June 2018

Objective

To assess differences between subjects with vs. without mixed features in major affective disorders.

Methods

In 3099 out‐patient subjects with DSM‐5 major depressive disorder (MDD, n = 1921) or bipolar disorders (BD, n = 1178), we compared those with (Mx) vs. without (Non‐Mx) mixed features (agitated‐irritable depression or dysphoric [hypo]mania) in an index episode.

Results

Prevalence of Mx averaged 21.9% [CI: 20.5–23.4] overall, ranking: BD‐II > BD‐I > MDD, and in BD depression ≥ [hypo]mania > MDD. Mx subjects were significantly more likely than Non‐Mx cases to (i) have other mixed episodes, (ii) have higher irritable and agitated ratings, (iii) have more substance abuse, (iv) switch into mixed episodes, (v) have more suicide attempts and higher suicidal ratings, (vi) change diagnosis from depression to BD, (vii) have higher hypomania scores when depressed or depression scores when [hypo]manic, (viii) be unmarried or separated with fewer children and siblings, (ix) be diagnosed more with BD than MDD, (x) be unemployed, (xi) have BD, suicide and divorce among first‐degree relatives, (xii) be female, (xiii) be younger at illness‐onset. Both BD and MDD Mx subjects also received antidepressants less, but antipsychotics and mood‐stabilizers more, alone and in combination with antidepressants.

Conclusions

Mood disorder subjects with agitated‐irritable depression or dysphoric [hypo]mania differed from those without such mixed features, including having a less favorable clinical course and repeated mixed episodes. They may represent a distinct and prevalent, syndromal clinical subtype with prognostic and therapeutic significance.
Complaints about dental practitioners: an analysis of 6 years of complaints about dentists, dental prosthetists, oral health therapists, dental therapists and dental hygienists in Australia
Authors: Thomas LA , Tibble H , Too LS , Hopcraft MS , Bismark MM
Published: June 2018

Background

Previous research has found dental practitioners at elevated risk of complaint compared with other health professions. This study aimed to describe the frequency, nature and risk factors for complaints involving dental practitioners.

Methods

We assembled a national dataset of complaints about registered health practitioners in Australia between January 2011 and December 2016. We classified complaints into 23 issues across three domains: health, performance and conduct. We compared rates of complaints about dental practitioners and other health practitioners. We used negative binomial regression analysis to identify factors associated with complaints.

Results

Dental practitioners made up 3.5% of health practitioners, yet accounted for approximately 10% of complaints. Dental practitioners had the highest rate of complaints among fourteen health professions (42.7 per 1000 practitioners per year) with higher rates among dentists and dental prosthetists than allied dental practitioners. Male practitioners were at a higher risk of complaints. Most complaints about dentists related to treatments and procedures (59%). Around 4% of dentists received more than one complaint, accounting for 49% of complaints about dentists. In 60% of closed cases no regulatory action was required. Around 13% of complaints resulted in restrictive actions, such as conditions on practice.

Conclusion

Improved understanding of patterns may assist regulatory boards and professional associations to ensure competent practice and protect patient safety.
Ultrastructure of the tubular glands in the isthmus region of the oviduct in laying and natural moulting commercial egg‐type chickens
Authors: Madekurozwa Mary‐Cathrine Nyasha , Mpango Mike M.
Published: June 2018

The study investigated the ultrastructural characteristics of tubular gland and duct cells, as well as luminal gland cells in the isthmus region of the oviduct of laying and natural moulting hens. Tubular glands in laying birds were composed of type 1 and 2 cells. Based on the preponderance of each cell type, in relation to the location of a developing egg in the oviduct of the domestic fowl, these gland cells may represent different functional states of the same cell. The findings of the study on natural moulting birds suggest that autophagy is a process confined to the early stages of degeneration, while necrosis occurs in the terminal stages.
Shortage of dentists in Outer Regional and Remote areas and long public dental waiting lists: Changes over the past decade
Authors: Dudko Yevgeni , Kruger Estie , Tennant Marc
Published: June 2018

Objective

The shortage of dentists in Outer Regional and Remote areas of Australia and long public dental waiting lists have been the subject of media attention over the last decade. A number of state and federal initiatives were introduced over the years to address these problems. This study aims to gauge whether the waiting lists and shortage of dentists in Outer Regional and Remote areas have seen a positive change over the last decade.

Design

This evaluation study analysed and compared the number of dentists full‐time equivalent per 100 000 population, eligible population and waiting list size (New South Wales and Queensland) at various points in time over the last decade.

Setting

National.

Participants

Data were extracted from practitioner registry reports.

Main outcome measures

Number of dentists practising in Outer Regional and Remote areas of Australia and number of people on the public dental waiting list (New South Wales and Queensland).

Results

There was a significant improvement in the number of dentists practising in Outer Regional and Remote areas of Australia. The public dental waiting lists in New South Wales and Queensland (as of September 2016) were found to have surpassed their pre National Partnership Agreement levels in 2012. The growth of public dental waiting lists exceeded the growth of the eligible population by a significant margin.

Conclusion

The dentist‐to‐population ratios in Outer Regional and Remote areas have seen a significant improvement. The reduction in the number of people on the public dental waiting list was significant, but brief.
Functional significance and risk factors for lymphocele formation after renal transplantation
Authors: Heer Munish K. , Clark David , Trevillian Paul R. , Sprott Philip , Palazzi Kerrin , Hibberd Adrian D.
Published: June 2018

Background

Lymphocele development following renal transplantation is a significant adverse event. It may cause acute graft dysfunction or venous obstruction. There are no consistent risk factors reported in literature. Perioperative fluid balance may lead to increased lymphocele formation and has never been studied. We aimed to analyse incidence and risk factors for lymphocele formation. We hypothesized that overhydration in perioperative period is a risk factor.

Methods

We analysed 250 consecutive renal transplant recipients from 2006 to 2014. All recipients had undergone protocol screening by computerized tomography and ultrasound scan at 3 months post‐transplant. We analysed risk factors for lymphocele formation. Comparisons between lymphocele and no‐lymphocele groups were made with binary logistic regression analyses. Renal function was compared between treated, untreated and no‐lymphocele groups with linear regression analyses.

Results

Thirty‐one of 250 (12.4%) transplant recipients developed lymphocele. Fourteen of 31 (45.4%) recipients required intervention due to symptoms (venous obstruction being the most common). Surgical drainage was done in all symptomatic patients (11 laparoscopic and three open). Two of 11 (18%) recipients had recurrence after laparoscopic drainage. There were no significant differences in risk factors between the lymphocele and no‐lymphocele groups. Renal function was comparable between no‐lymphocele and treated lymphocele groups. Untreated lymphocele group trended towards better graft function at 1 year (P = 0.051).

Conclusion

Post‐transplant lymphocele developed one in eight transplant recipients and tended to occur in those with good renal function. Around half of the recipients with lymphocele required intervention with good recovery of long‐term renal function. No risk factor for lymphocele development was established.
Increased risk of open‐angle glaucoma among patients with diabetes mellitus: a 10‐year follow‐up nationwide cohort study
Authors: Rim Tyler Hyungtaek , Lee Sang Yeop , Bae Hyoung Won , Seong Gong Je , Kim Sung Soo , Kim Chan Yun
Published: June 2018

Purpose

To evaluate the risk of open‐angle glaucoma among patients with diabetes.

Methods

This retrospective propensity score‐matched cohort study included patients with diabetes and a matched comparison group from the Korean National Health Insurance Service National Health Screening Cohort, which includes approximately 500 000 adults aged ≥40 years. Nondiabetes group was matched to diabetes group in a 1:1 ratio using a propensity score based on age, sex, comorbidities, antihypertensive medication use and medical care visits. Each group was followed from January 1, 2004 to either the date of developing open‐angle glaucoma or the date of last follow‐up in 2013.

Results

Incidence of open‐angle glaucoma was 20.0/10 000 person‐years in diabetes group (n = 58 358) and 17.0/10 000 person‐years in nondiabetes group (n = 58 358). Age‐ and sex‐ adjusted hazard ratio (HR) was 1.19 (95% confidence interval [CI], 1.09–1.30). In the subgroup analyses, diabetes was associated with an increased risk of open‐angle glaucoma in both younger and older age groups (HR = 1.20 for those aged 40–59 years and HR = 1.18 for those aged 60–79 years) and in both sexes (men, HR = 1.13; women, HR = 1.27).

Conclusion

Patients diagnosed with diabetes were more likely to develop open‐angle glaucoma compared with patients without diabetes.
Early central line‐associated blood stream infections in children with cancer pose a risk for premature catheter removal
Authors: Moell Jacob , Svenningsson Anna , Af Sandeberg Margareta , Larsson Magnus , Heyman Mats , Harila‐Saari Arja , Nilsson Anna
Published: June 2018

Aim

This study examined the clinical characteristics of central line‐associated blood stream infections occurring within 30 days after insertion versus later infections in paediatric cancer patients and the subsequent risk for premature catheter removal.

Methods

This was a retrospective study of children aged 0–18 years who were diagnosed with cancer from 2013 to 2014 at the Astrid Lindgren Children Hospital, Sweden. Clinical and microbiology data for each patient were collected for 365 days after the central venous catheter (CVC) was inserted.

Results

During the study period, 154 children received a CVC. The overall incidence of central line associated blood stream infections was 2.0 per 1000 catheter days. A total of 108 infectious episodes were identified in 44/154 (29%) patients. Of those, 15/44 children (29%) had an early infection within 30 days and alpha‐haemolytic Streptococci and coagulase‐negative Staphylococci dominated. Children with early infections were more likely to have a haematological malignancy and to need premature removal of the CVC due to repeated infections.

Conclusion

We observed a high prevalence of early CVC associated blood stream infection mainly in patients with haematological malignancies. Our study highlights the importance of preventive measures in reducing infections in paediatric cancer patients.
Long‐term adverse effects of paracetamol – a review
Authors: McCrae J. C. , Morrison E. E. , MacIntyre I. M. , Dear J. W. , Webb D. J.
Published: June 2018

Paracetamol (acetaminophen) is the most commonly used drug in the world, with a long record of use in acute and chronic pain. In recent years, the benefits of paracetamol use in chronic conditions has been questioned, notably in the areas of osteoarthritis and lower back pain. Over the same period, concerns over the long‐term adverse effects of paracetamol use have increased, initially in the field of hypertension, but more recently in other areas as well. The evidence base for the adverse effects of chronic paracetamol use consists of many cohort and observational studies, with few randomized controlled trials, many of which contradict each other, so these studies must be interpreted with caution. Nevertheless, there are some areas where the evidence for harm is more robust, and if a clinician is starting paracetamol with the expectation of chronic use it might be advisable to discuss these side effects with patients beforehand. In particular, an increased risk of gastrointestinal bleeding and a small (~4 mmHg) increase in systolic blood pressure are adverse effects for which the evidence is particularly strong, and which show a degree of dose dependence. As our estimation of the benefits decreases, an accurate assessment of the harms is ever more important. The present review summarizes the current evidence on the harms associated with chronic paracetamol use, focusing on cardiovascular disease, asthma and renal injury, and the effects of in utero exposure.
Gastrointestinal bleeding risk of selective serotonin reuptake inhibitors by level of kidney function: A population‐based cohort study
Authors: Iwagami Masao , Tomlinson Laurie A. , Mansfield Kathryn E. , Douglas Ian J. , Smeeth Liam , Nitsch Dorothea
Published: June 2018

Aim

To estimate the risk of gastrointestinal (GI) bleeding associated with serotonin reuptake inhibitors (SSRIs) by level of kidney function.

Methods

We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics. We identified patients with chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml min–1 1.73 m–2 for ≥3 months), and a comparison group of patients without it. Patients with CKD were further classified as stage 3a (eGFR 45–59 ml min–1 1.73 m–2), 3b (30–44 ml min–1 1.73 m–2) and 4/5 (<30 ml min–1 1.73 m–2). We excluded prevalent SSRI users at cohort entry. Exposure was time‐dependent SSRI prescription and outcome was first hospitalization for GI bleeding. We estimated adjusted rate ratio (aRR) and rate difference (aRD) of GI bleeding comparing periods with and without SSRI prescription at each level of kidney function.

Results

The aRRs and aRDs were: (i) no CKD (n = 202 121) aRR: 1.66 (95%CI 1.37–2.01), aRD: 2.0/1000 person–years (5.5 vs. 3.5/1000 person–years in period with and without SSRIs); (ii) CKD stage 3a (n = 153 316) aRR: 1.86 (1.62–2.15), aRD: 4.2/1000 person–years (8.3 vs. 4.1/1000 person–years); (iii) CKD stage 3b (n = 46 482) aRR: 1.61 (1.27–2.04), aRD: 4.8/1000 person–years (9.9 vs. 5.1/1000 person–years); and (iv) CKD stage 4/5 (n = 11 197) aRR: 1.84 (1.14–2.96), aRD: 7.9/1000 person–years (15.3 vs. 7.4/1000 person–years). While there was no evidence of increase in the aRR (P = 0.922), there was strong evidence that the aRD increased as kidney function deteriorated (P = 0.001).

Conclusions

While the relative risk was constant, the excess risk of GI bleeding associated with SSRIs markedly increased among patients with decreased kidney function.
Enhanced taxane uptake into bladder tissues following co‐administration with either mitomycin C, doxorubicin or gemcitabine: association to exfoliation processes
Authors: Pandey Rakhi , Jackson John K. , Liggins Richard , Mugabe Clement , Burt Helen M.
Published: June 2018

Objective

To investigate the effect of three anticancer drugs (mitomycin c (MMC), doxorubicin or gemcitabine) on bladder wall morphology and the uptake of paclitaxel or docetaxel following coadministration. The primary objective of this study was to measure the uptake of MMC, doxorubicin or gemcitabine with or without exposure of the tissue to amine terminated cationic nanoparticles (CNPs) and to investigate any possible exfoliation effects of the three drugs on intact bladder tissue. The secondary objective was to investigate the uptake of taxane drugs (docetaxel, DTX) and paclitaxel, (PTX) from surfactant micelle formulations in the presence of MMC, doxorubicin or gemcitabine.

Materials and Methods

Sections of fresh pig bladder tissue were incubated in Franz diffusion cells with the urothelial side exposed to solutions of doxorubicin, MMC and gemcitabine containing radioactive drug for 90 min. Some tissue samples were simultaneously exposed to each of the three drugs in combination with the surfactant micelle formulations of PTX (Taxol) or DTX (Taxotere). Tissue sections were then cryostat sectioned for drug quantitation by liquid scintillation counting or fixed for scanning electron microscopy and haematoxylin and eosin staining.

Results

All three drugs caused exfoliation of the urothelial layer of bladder tissues. Drug uptake studies showed that all three drugs effectively penetrated the lamina propria through to the muscular layer over a 2‐h incubation and these levels were unaffected by pre‐treatment with CNPs. The uptake levels of the taxane drugs PTX and DTX were significantly enhanced following simultaneous treatment of bladders with MMC, doxorubicin or gemcitabine.

Conclusion

The exfoliation effects of MMC, doxorubicin and gemcitabine allow for good tissue penetration of these drugs with no additional effect from CNP treatment of bladders. The observed exfoliation effect of these amine‐containing drugs probably arises from a cationic interaction with the mucus and urothelium cell layer in a manner similar to that previously reported for CNPs. These studies suggest that the lack of long‐term clinical efficacy of these drugs may not arise from poor intravesical drug penetration but may result from a rapid diffusion of the drugs into the deeper vascularised muscular region with rapid drug clearance. The enhanced uptake of PTX or DTX following co‐administration with MMC, doxorubicin or gemcitabine probably arises from the removal of the urothelial barrier by exfoliation allowing for improved taxane partitioning into superficial layers. These effects may allow for dual drug intravesical strategies offering greatly improved taxane uptake and potential additive drug effects for improved efficacy.
Insect outbreaks alter nutrient dynamics in a southern African savanna: patchy defoliation ofColophospermum mopanesavanna byImbrasia belinalarvae
Authors: de Swardt Donovan B. , Wigley‐Coetsee Corli , O'Connor Timothy G.
Published: June 2018

Invertebrate herbivore outbreaks have important impacts on system biogeochemical cycling, but these effects have been poorly documented in African savanna ecosystems. In semi‐arid African savannas, outbreaks of the lepidopteranImbrasia belina(mopane worm) affect discrete patches of the dominantColophospermum mopanetrees; larvae may completely defoliate trees for up to six weeks during each of the early and late growing seasons. We studied the impact of mopane worm outbreaks on the availability of nitrogen (N), phosphorus (P), and potassium (K) within mopane savanna by quantifying major nutrient pools in defoliated and non‐defoliated savanna patches, including leaves, leaf litter, worm frass, and the soil beneath trees. Within an outbreak area, approximately 44 percent of trees were infested, supporting ~29,000 worms/ha, leading to ~640 kg/ha dry weight frass deposition at 1.4 g of frass/day‐individual (fourth or fifth instar), compared with an average 1645 kg/ha dry weight of leaf on trees most of which should be deposited by litterfall at the end of the growing season. Frass had twofold higher P, 10 percent higher K, but equivalent N content than litter. Taking frass and litter deposition together, the N, P, and K contents added due to the outbreak event at our study site were 0.88, 5.8, and 2.8 times those measured in non‐outbreak patches, a pattern which was reflected in the nutrient contents of soil surfaces beneath defoliated trees. Invertebrate herbivory appears to be an important driver for mopane savanna but has been largely neglected.
Dental health aides in Alaska: A qualitative assessment to improve paediatric oral health in remote rural villages
Authors: Senturia Kirsten , Fiset Louis , Hort Kim , Huebner Colleen , Mallott Elizabeth , Milgrom Peter , Nelson Lonnie , Parrish Canada , Cunha‐Cruz Joana
Published: June 2018

Objective

Isolated villages in Alaska face disparities in oral health and access to care. Dental health aides such as the primary dental health aide (PDHA) and the dental health therapist (DHAT) fill a critical role for providing dental care in Alaska. Our objective was to describe strengths and barriers to paediatric dental care for children living in remote Alaska villages from the perspectives of the community and the health care system.

Methods

This qualitative study collected data through semi‐structured key informant interviews with community members (n = 19) and healthcare workers (n = 19) and focus groups with patients (n = 31 adolescents and 16 caregivers of children under 12 years) living in or providing health care to 3 remote villages in Alaska. Using an inductively developed codebook and a narrative approach, 3 researchers independently read and thematically analysed the transcripts.

Results

Two themes emerged: (i) PDHAs and DHATs are perceived as sustainable and strongly positioned to meet the unique dental needs of the rural communities; (ii) PDHAs and DHATs face barriers that limit their effectiveness, and their distinct roles require clarification and administrative support.

Conclusions

Dental health aides, both PDHAs and DHATs, are well accepted in Alaska villages. An innate understanding of cultural norms and continuity of care are key elements driving village satisfaction. The potential exists administratively to strengthen the model with the implementation of clinical and office‐system strategies to increase efficiency of the dental team. Culturally adapted implementation strategies will be critical to the successful expansion of new workforce models that are addressing health disparities.
Self‐control and dental caries among elementary school children in Japan
Authors: Matsuyama Yusuke , Fujiwara Takeo , Ochi Manami , Isumi Aya , Kato Tsuguhiko
Published: June 2018

Objectives

Children's self‐control is associated with various behaviour‐related health problems in childhood and later in life. However, studies on self‐control and dental caries, strongly associated with toothbrushing or drinking and eating behaviour, are limited. We investigated the association between self‐control and the number of decayed or filled primary teeth (dft) among first‐grade children (6‐7 years old) in Japan and evaluated the mediation effect of oral health behaviour on this association.

Methods

A cross‐sectional study of all first‐grade elementary school children and their caregivers in Adachi ward (Tokyo) was conducted in 2015. Clinically determined dft status among children and caregiver‐administered questionnaires on self‐control was linked (n = 4291; valid response rate = 80.1%). Self‐control was assessed by the following single question: “in the last month, was your child able to give up on things they want or do things that they do not like to do for better future outcomes?” Poisson regression analysis was conducted adjusting for age in months, sex, parental educational attainment and household income. Mediation analysis was performed to evaluate the mediation effects of toothbrushing frequency, frequency of drinking sugar‐sweetened beverages and snack‐eating habits on the association.

Results

Lower self‐control was associated with higher dft after adjusting for all covariates (mean ratio = 1.09; 95% CI: 1.06, 1.12). Toothbrushing frequency, frequency of drinking sugar‐sweetened beverages and snack‐eating habits mediated 18.1%, 36.1% and 38.3% of the association between self‐control and dft, respectively.

Conclusions

Strengthening children's self‐control might decrease their dental caries by improving their oral health behaviour.
Scottish Bowel Screening Programme colonoscopy quality – scope for improvement?
Authors: Quyn A. J. , Fraser C. G. , Stanners G. , Carey F. A. , Rees C. J. , Moores B. , Steele R. J.
Published: June 2018

Aim

The delivery of the Scottish Bowel Screening Programme (SBoSP) is rooted in the provision of a high quality, effective and participant‐centred service. Safe and effective colonoscopy forms an integral part of the process. Additional accreditation as part of a multi‐faceted programme for participating colonoscopists, as in England, does not exist in Scotland. This study aimed to describe the quality of colonoscopy in the SBoSP and compare this to the English national screening standards.

Methods

Data were collected from the SBoSP between 2007 and 2014. End‐points for analysis were caecal intubation, cancer, polyp and adenoma detection, and complications. Overall results were compared with 2012 published English national standards for screening and outcomes from 2006 to 2009.

Results

During the study period 53 332 participants attended for colonoscopy. The colonoscopy completion rate was 95.6% overall. The mean cancer detection rate was 7.1%, the polyp detection rate was 45.7% and the adenoma detection rate was 35.5%. The overall complication rate was 0.47%.

Conclusion

Colonoscopy quality in the SBoSP has exceeded the standard set for screening colonoscopy in England, despite not adopting a multi‐faceted programme for screening colonoscopy. However, the overall adenoma detection rate in Scotland was 9.1% lower than that in England which has implications for colonoscopy quality and may have an impact on cancer prevention rates, a key aim of the SBoSP.
Acute effect of wearing compression stockings on lower leg swelling and muscle stiffness in healthy young women
Authors: Sugahara Ikumi , Doi Misaki , Nakayama Rinko , Sasaki Kazushige
Published: June 2018

Compression stockings are known to be effective in reducing peripheral oedema or leg swelling by increasing tissue pressure and venous blood flow. While previous studies on compression stockings have focused on its prolonged, preventive effect on leg swelling, the aim of this study was to investigate an acute effect of wearing compression stockings on lower leg swelling and muscle stiffness. Twenty healthy women aged 18–23 years participated in the experiment conducted in the evening, in which they wore below‐knee graduated compression stockings and rested in a seated position for 30 min. Before and after the application of stockings, maximum calf circumference, volume, extracellular water resistance (RECW) and muscle stiffness of the right lower leg were determined by tape measure, water displacement volumetry, segmental bioelectrical impedance spectroscopy and ultrasound shear‐wave elastography, respectively. The maximum calf circumference and the reciprocal of RECW (an index of extracellular fluid volume) significantly decreased after the application of stockings, whereas the total lower leg volume and the stiffness (shear modulus) of the medial gastrocnemius muscle tended to decrease. These changes, except for that in the medial gastrocnemius muscle stiffness, were opposite to those from morning to evening studied in the subgroup of participants (n = 8). However, partial correlation analysis failed to detect significant associations among these changes. These results suggest that even for a short period of application, compression stockings have some positive effects against lower leg swelling.
“We Are Not Starving:” Challenging Genetically Modified Seeds and Development in Ghana
Authors: Rock Joeva
Published: June 2018

In the last decade, the number of African countries researching and growing genetically modified seeds (GMOs) has increased fourfold. These efforts are backed by an international consortium of donors who broker agreements between biotechnology companies and African state scientists to lease genetic material for use. Given the involvement of African scientists, proponents argue that these projects are homegrown and necessary to feed the African continent. However, in Ghana, where GM cowpea and rice are currently under field trial, both Ghanaian scientists and anti‐GMO activists are unsatisfied with donor‐constructed realities. Instead, these unlikely bedfellows challenge the discourses that circulate through international development circuits by pointing to a history of both colonial exploitation and sovereign dreams. By doing so, Ghanaian scientists and activists articulate alternative visions for a food sovereign, postcolonial future.
Global development and adaptive behaviour in children with early‐onset epilepsy: a population‐based case–control study
Authors: Reilly Colin , Atkinson Patricia , Memon Ayesha , Jones Chloe , Dabydeen Lyvia , Das Krishna B , Gillberg Christopher , Neville Brian G R , Mahoney J Matthew , Scott Rod C
Published: June 2018

Aim

There are limited population‐based data on global development and adaptive behaviour in children with early‐onset epilepsy. The aims of this study were: (1) to identify the prevalence of deficits in global development and adaptive behaviour experienced by children with early‐onset epilepsy; (2) to identify factors associated with such deficits; and (3) to compare the relationship between measures of neurodevelopment in the group with epilepsy to a group without epilepsy who had other neurological or neurodevelopmental difficulties.

Method

The Sussex Early Epilepsy and Neurobehaviour study is a prospective, community‐based study involving children (1–7y) with epilepsy. We undertook comprehensive psychological assessment with participants, including measures of global development and adaptive behaviour. We compared the children with epilepsy with a sex, age, and developmentally‐matched group of children without epilepsy who had neurodevelopmental or neurological difficulties using correlation matrices.

Results

Forty‐eight children (91% of the eligible population) with epilepsy underwent assessment. Seventy‐one per cent of children displayed delayed global development (<2SD) and 56% showed significant deficits (<2SD) in adaptive behaviour. Our analysis revealed that non‐white ethnicity and use of polytherapy were independently associated with decreased scores on measures of global development and adaptive behaviour. The correlations between measures of developmental functioning were higher in children with epilepsy than in those without.

Interpretation

Children with early‐onset epilepsy frequently have difficulties with global development and adaptive behaviour. The higher correlations between neurodevelopmental measures in children with epilepsy suggest that the profile in children with epilepsy is different. This may have significant implications for both neuropathology and interventions.

What this paper adds

Children with early‐onset epilepsy are at significant risk of intellectual disability.

Developmental impairment is associated with use of polytherapy but not with any seizure parameters.

Developmental profiles in young children with epilepsy differ from other conditions.
Differential effects of the circadian system and circadian misalignment on insulin sensitivity and insulin secretion in humans
Authors: Qian Jingyi , Dalla Man Chiara , Morris Christopher J. , Cobelli Claudio , Scheer Frank A. J. L.
Published: June 2018

Glucose tolerance is lower at night and higher in the morning. Shift workers, who often eat at night and experience circadian misalignment (i.e. misalignment between the central circadian pacemaker and the environmental/behavioural cycles), have an increased risk of type 2 diabetes. To determine the separate and relative impacts of the circadian system, behavioural/environmental cycles, and their interaction (i.e. circadian misalignment) on insulin sensitivity and β‐cell function, the oral minimal model was used to quantitatively assess the major determinants of glucose control in 14 healthy adults using a randomized, cross‐over design with two 8‐day laboratory protocols. Both protocols involved 3 baseline inpatient days with habitual sleep/wake cycles, followed by 4 inpatient days with the same nocturnal bedtime (circadian alignment) or with 12‐hour inverted behavioural/environmental cycles (circadian misalignment). The data showed that circadian phase and circadian misalignment affect glucose tolerance through different mechanisms. While the circadian system reduces glucose tolerance in the biological evening compared to the biological morning mainly by decreasing both dynamic and static β‐cell responsivity, circadian misalignment reduced glucose tolerance mainly by lowering insulin sensitivity, not by affecting β‐cell function.
Short‐ and long‐term administration of the non‐steroidal mineralocorticoid receptor antagonist finerenone opposes metabolic syndrome‐related cardio‐renal dysfunction
Authors: Lachaux Marianne , Barrera‐Chimal Jonatan , Nicol Lionel , Rémy‐Jouet Isabelle , Renet Sylvanie , Dumesnil Anais , Wecker Didier , Richard Vincent , Kolkhof Peter , Jaisser Frederic , Ouvrard‐Pascaud Antoine , Mulder Paul
Published: June 2018

Aim

To determine whether non‐steroidal mineralocorticoid receptor (MR) antagonists oppose metabolic syndrome‐related end‐organ, i.e. cardiac, damage.

Materials and methods

In Zucker fa/fa rats, a rat model of metabolic syndrome, we assessed the effects of the non‐steroidal MR antagonist finerenone (oral 2 mg/kg/day) on left ventricular (LV) function, haemodynamics and remodelling (using echocardiography, magnetic resonance imaging and biochemical methods).

Results

Long‐term (90 days) finerenone modified neither systolic blood pressure nor heart rate, but reduced LV end‐diastolic pressure and LV end‐diastolic pressure‐volume relationship, without modifying LV end‐systolic pressure and LV end‐systolic pressure‐volume relationship. Simultaneously, long‐term finerenone reduced both LV systolic and diastolic diameters, associated with reductions in LV weight and LV collagen density, while proteinuria and renal nGAL expression were reduced. Short‐term (7 days) finerenone improved LV haemodynamics and reduced LV systolic diameter, without modifying LV diastolic diameter. Moreover, short‐term finerenone increased myocardial tissue perfusion and reduced myocardial reactive oxygen species, while plasma nitrite levels, an indicator of nitric oxide (NO) bio‐availability, were increased.

Conclusions

In rats with metabolic syndrome, the non‐steroidal MR antagonist finerenone opposed metabolic syndrome‐related diastolic cardiac dysfunction and nephropathy. This involved acute effects, such as improved myocardial perfusion, reduced oxidative stress/increased NO bioavailability, as well as long‐term effects, such as modifications in the myocardial structure.
Efficacy and safety of ipragliflozin as an add‐on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial
Authors: Han Kyung‐Ah , Chon Suk , Chung Choon Hee , Lim Soo , Lee Kwan‐Woo , Baik SeiHyun , Jung Chang Hee , Kim Dong‐Sun , Park Kyong Soo , Yoon Kun‐Ho , Lee In‐Kyu , Cha Bong‐Soo , Sakatani Taishi , Park Sumi , Lee Moon‐Kyu
Published: June 2018

Aim

To evaluate the efficacy and safety of ipragliflozin vs placebo as add‐on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM).

Methods

This double‐blind, placebo‐controlled, multi‐centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT).

Results

In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add‐on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were −0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference −0.83% [95% CI −1.07 to −0.59]; P < .0001). More ipragliflozin‐treated patients than placebo‐treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference −1.64 mmol/L, −1.50 μU/mL, −1.72 kg, and −0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted.

Conclusions

Ipragliflozin as add‐on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM.
Mapping of biguanide transporters in human fat cells and their impact on lipolysis
Authors: Arner Peter , Kulyté Agné , Batchelor Kenneth , Laurencikiene Jurga , Livingston James , Rydén Mikael
Published: June 2018

Aim

To examine the cell membrane transporters involved in mediating the antilipolytic effect of biguanides in human fat cells.

Materials and methods

Gene expression of biguanide transporters was mapped in human subcutaneous adipose tissue and in adipocytes before and after differentiation. Those expressed in mature fat cells were knocked down by RNA interference (RNAi) and the antilipolytic effects of metformin and two novel, highly potent biguanides, NT1014 and NT1044, were examined.

Results

Analysis of the transporter affinity of biguanides in HEK293 cells overexpressing individual transporters showed that NT1014 and NT1044 had >10 times higher affinity than metformin. Animal studies showed that NT1014 was >5 times more potent than metformin in lowering plasma glucose in mice. In human fat cells, the novel biguanides displayed higher AMP‐activated protein kinase activation and antilipolytic efficacy than metformin. Five transporters, organic cation transporter (OCT)1 (SLC22A1), organic cation transporter novel type 1 (OCTN1; SLC22A4), OCT3 (SLC22A3), plasma membrane monoamine transporter (PMAT; SLC29A4) and multidrug and toxin extrusion transporter (MATE1; SLC47A1), were detectable in fat cells but only OCT3, PMAT and MATE1 increased during adipogenesis in vitro and were enriched in fat cells compared with other adipose cell types. Gene knockdown by RNAi showed that MATE1 and PMAT reduction attenuated the antilipolytic effect of metformin but only PMAT knockdown decreased the effect of all three biguanides.

Conclusions

While human fat cells primarily express three biguanide transporters, our data suggest that PMAT is the primary target for development of fat cell‐specific antilipolytic biguanides with high sensitivity and potency.
Contribution of basal and postprandial hyperglycaemia in type 2 diabetes patients treated by an intensified insulin regimen: Impact of pump therapy in the OPT2mise trial
Authors: Reznik Yves , Habteab Aklilu , Castaneda Javier , Shin John , Joubert Michael
Published: June 2018

Aims

The relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) in type 2 diabetes patients treated with multiple daily injections (MDI) of insulin is poorly documented. In this study, the BHG and PPHG of patients from the OPT2mise study who were initially treated with MDI were assessed before randomization and again after 6 months of continuous subcutaneous insulin infusion (CSII).

Materials and Methods

Blinded continuous glucose monitoring (CGM) data were collected in 259 MDI patients after completion of an 8‐week run‐in period. The hyperglycaemic area under the curve (AUC) during the 24‐hour basal period (AUC‐B) and the postprandial period (AUC‐P) were compared with analysis of variance based on contribution to total hyperglycaemia in HbA1c groups (Group 1, <8%; Group 2, 8%‐8.4%; Group 3, 8.5%‐8.9%; Group 4, 9%‐9.4%; Group 5, ≥9.5%). Changes in AUC‐B and AUC‐P were assessed after 6 months of pump therapy in 131 randomized participants with available CGM recordings.

Results

In patients undergoing MDI therapy, AUC‐B was 21.6% to 54.8% lower in Group 4 to 1 (P = .0138 and P = .0002, respectively) in comparison to Group 5. In contrast, AUC‐P did not differ among HbA1c groups (P = .1009). HbA1c correlated with AUC‐B, but not with AUC‐P. After switching to CSII, AUC‐B and AUC‐P decreased by 21% and 17%, respectively. When comparing responders with non‐responders to CSII therapy, no between‐group differences were observed in AUC‐B and AUC‐P.

Conclusions

Basal hyperglycaemia is the major determinant of overall exposure to hyperglycaemia in type 2 diabetes with MDI failure.
Application of double low dose combined low flow injection in coronary dual‐source coronary computed tomography angiography
Authors: Tang Zhenhua
Published: June 2018

Purpose

This study was aimed to explore the feasibility of lower tube voltage, low volumes of contrast medium, and low flow injection in prospective electrocardiogram (ECG)‐triggered high‐pitch dual‐source coronary computed tomography angiography (CCTA) for coronary artery imaging.

Material and Methods

A total of 140 patients with body mass index (BMI) ranging from 18.5 to 24.3 kg/m2 and heart rate (HR) lower than 65 times/min underwent CCTA were divided randomly into two groups. The enhanced CT value and noise as well as signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) were calculated. Coronary artery was evaluated by double‐blind method using a four‐point grading scale.

Results

No significant differences were found in the average enhanced CT value, noise, SNR, and CNR of all segments between the two groups (P > .05). Meanwhile, effective radiation dosages in group A were markedly lower than those in group B (P < .01).

Conclusion

The prospective ECG‐triggered high‐pitch dual‐source CCTA with low voltage, contrast medium, and flow rate injection using sinogram affirmed iterative reconstruction is feasible which can observably reduce radiation and obtain satisfactory images.
‘Stop‐go’ policy and the restriction of postwar British house‐building
Authors: Scott Peter M. , Walker James T.
Published: June 2018

From the mid‐1950s to the early 1980s the Treasury and the Bank of England successfully advocated a policy of restricting both private and public sector house‐building, as a key but covert instrument of their wider ‘stop‐go’ macroeconomic policy framework. While the intensity of restrictions varied over the economic cycle, private house‐building was restricted (through limiting mortgage availability) for almost all this period. This was achieved by keeping building society interest rates low relative to other interest rates and thus starving the building society movement of mortgage funds. Mortgage restriction was never publicly discussed and sometimes operated alongside ambitious housing targets and well‐publicized policy initiatives to boost housing demand. This article outlines the evolution of house‐building restriction, together with its impacts on the housing sector and the wider economy. We review the evolution of the policy framework and its consequences, compare the level and stability of British house‐building during this period—historically and relative to other countries—and undertake time‐series econometric analysis of its impacts on both house‐building and house prices. Finally, implications for debates regarding stop‐go policy, Britain's housing problem, and the distributional consequences of government macroeconomic policy are discussed.