bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns
Authors: Martino‐Andrade A. J. , Liu F. , Sathyanarayana S. , Barrett E. S. , Redmon J. B. , Nguyen R. H. N. , Levine H. , Swan S. H. ,   the TIDES Study Team
Published: April 2016

Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS) and anopenile distance (AGPAP) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono‐2‐ethyl‐5‐oxohexyl (MEOHP, β=−0.48; 95% confidence interval, −0.93, −0.02), MEHHP (−0.48; −0.92, −0.05), mono‐2‐ethyl‐5‐carboxypentyl (MECPP, −0.51; −1.01, −0.004), although no appreciable associations were seen between PW and T1 and T3 DEHP metabolite concentrations in this subset. Concentrations of DEHP metabolites in T1 urine samples were inversely related to male AGD. For example, in T1 samples in this subset of women mono‐2‐ethyl‐5‐hydroxyhexyl (MEHHP) was inversely associated with male AGDAP (β = −1.73; 95% confidence interval, −3.45, 0.0004). However, no appreciable associations were seen between AGD measures and any DEHP metabolite in T2 and T3 samples. These data suggest that DEHP exposure is inversely associated with AGD and PW, with PW primarily associated with T2 exposure and AGD associations seen only for T1 exposure, but no associations were found between T3 DEHP metabolites and any of these genital endpoints. These findings are consistent with data on critical windows in rodent studies, supporting the biological plausibility of these associations in humans.
A high‐fat diet negatively affects rat sperm mitochondrial respiration
Authors: Ferramosca A. , Conte A. , Moscatelli N. , Zara V.
Published: April 2016

Recent evidences have linked abdominal obesity, insulin resistance, and dyslipidemia to male infertility. Since a defective energy metabolism may play an important role in the impairment of sperm quality, the aim of this study is to investigate the sperm energetic metabolism in rats fed with a high‐fat diet, an animal model associated with metabolic syndrome development. Sexually mature male Sprague–Dawley rats were divided into two groups and fed for 4 weeks a standard diet (control group) or a diet enriched in 35% of fat (high fat group). Liver and adipose tissue weight, plasma glucose, insulin, and lipid concentrations were determined. Activities of enzymes involved in sperm energetic metabolism were evaluated by spectrophotometric assays. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption. The administration of a high‐fat diet caused a significant increase in body weight of rats and provoked hyperglycemia, hyperinsulinemia, and dyslipidemia. In these animals, we also observed a reduction in sperm concentration and motility. The investigation of sperm energetic metabolism in animals fed a high‐fat diet revealed an impairment in the activity of pyruvate and lactate dehydrogenase, citrate synthase, and respiratory chain complexes. A parallel reduction in the cellular levels of adenosine triphosphate (ATP) and an increase in oxidative damage were also observed. A defective energy metabolism may play an important role in the impairment of sperm quality in the high‐fat diet fed rats.
Management of malignant colorectal polyps in New Zealand
Authors: Fischer Jesse , Dobbs Bruce , Dixon Liane , Eglinton Tim W. , Wakeman Christopher J. , Frizelle Frank A. ,   on behalf of the New Zealand Malignant Polyp Study (NZ MAPS) group
Published: April 2016

Background

The management of colorectal polyps containing a focus of malignancy is problematic, and the risks of under‐ and over‐treatment must be balanced. The primary aim of this study was to describe the management and outcomes of patients with malignant polyps in the New Zealand population; the secondary aim was to investigate prognostic factors.

Methods

Retrospective review of relevant clinical records at five New Zealand District Health Boards.

Results

Out of the 414 patients identified, 51 patients were excluded because of the presence of other relevant colorectal pathology, leaving 363 patients for analysis. Of these, 182 had a polypectomy, and 181 had a bowel resection as definitive treatment. The overall 5‐year survival was not altered with resection but was improved with re‐excision of any form (repeat polypectomy or bowel resection). There were 110 rectal lesions and 253 colonic lesions. A total of 16% of patients who had resection after polypectomy were found to have residual cancer in the resected specimen. Ischaemic heart disease, chronic obstructive pulmonary disease and metastatic disease were found to negatively impact overall survival (P < 0.001). Resection was more likely to follow polypectomy if polypectomy margins were positive, fragmentation occurred for sessile lesions and for pedunculated lesions with a higher Haggitt level.

Conclusion

Polypectomy is oncologically safe in selected patients. Re‐excision improves overall survival and should be considered in patients with low comorbidity (American Society of Anesthesiologists score 1 and 2) and where there is concern about margins (sessile lesions and positive polypectomy margins). In the majority of patients, however, no residual disease is found.
Plasma citrulline measurement in the diagnosis of acute mesenteric ischaemia
Authors: Kulu Rıdvan , Akyildiz Hizir , Akcan Alper , Oztürk Ahmet , Sozuer Erdogan
Published: April 2016

Background

The differential diagnosis in acute mesenteric ischaemia (AMI) is essential and sometimes life‐saving. A marker for early diagnosis is lacking. Citrulline is an amino acid mainly synthesized by small bowel enterocytes from glutamine. In this study, we aimed to evaluate the diagnostic and prognostic values of citrulline with those of the D‐dimer in patients with AMI.

Methods

The patients were divided into two groups; group 1: patients with acute abdominal findings which were attributed preoperatively to AMI, and group 2: patients with acute abdominal findings which were attributed preoperatively to causes other than AMI. All patients underwent surgical exploration. Blood samples were taken before surgery. The demographic features, laboratory examinations, citrulline concentration, D‐dimer level and surgical findings were evaluated.

Results

Overall, 48 patients were enrolled in the study. AMI was diagnosed in 23 of the 48 patients. There was no significant difference between the groups with regard to gender, leucocyte count and creatinine levels but group 1 was significantly older than group 2. Citrulline, D‐dimer and lactate levels were also significantly higher in group 1. Age, lactate, D‐dimer and citrulline levels were statistically significant for mortality. The most significant factor was increased lactate level at admission.

Conclusion

Plasma citrulline level may be helpful in the diagnosis of patients with AMI.
Outcome of bridge to surgery stenting for obstructive left colon cancer
Authors: Kim Min Ki , Kye Bong‐Hyeon , Lee In Kyu , Oh Seong Taek , Ahn Chang Hyeok , Lee Yoon Suk , Lee Sang Chul , Kang Won‐Kyung
Published: April 2016

Background

The aim of our study was to compare short‐ and long‐term outcomes of stent insertion followed by surgery with those of emergency surgery for left colon malignant obstructions.

Methods

The medical records of patients who received curative resection due to obstructive primary left colon cancer and who were diagnosed with stage II or III from January 2004 to December 2010 in six hospitals affiliated with The Catholic University of Korea were reviewed. One hundred and twelve patients in self‐expandable metallic stent (SEMS) group were matched to 56 patients in the emergency surgery (ES) group using propensity score matching method. Overall survival (OS) and disease‐free survival (DFS) were compared between the groups. Perioperative outcomes and pathologic results were also compared.

Results

Baseline characteristics were comparable between the two groups after matching. The analysis of perioperative outcomes showed short‐term advantages of stent insertion. Patients in the SEMS group were more likely (87.5 versus 75.0%, P = 0.049) to have a distal resection margin >5 cm. Harvesting ≥12 lymph nodes were more frequent (89.3 versus 71.4%, P = 0.007) in the SEMS group. Five‐year DFS was 69.5% in the SEMS group and 73.1% in the ES group (P = 0.464). Five‐year OS was not different between the groups (79.7 versus 77.7%, P = 0.989).

Conclusions

SEMS can be a reasonable therapeutic option for malignant obstruction in patients with left colon cancer until definitive conclusion about the long‐term survival effect of SEMS is made from further large‐scale prospective randomized trials.
Continuation of pregnancy despite a diagnosis of severe fetal anomaly: a retrospective French study
Authors: Madeuf Amelie , Roman Horace , Verspyck Eric
Published: April 2016

Introduction

The aim of this study was to describe diagnoses and outcomes when women choose to continue a pregnancy despite detection of severe fetal anomaly.

Material and methods

Retrospective study from a French national registry between 2005 and 2009. Various indication groups were classified based on a scale incorporating mortality and morbidity outcomes. Risk factors for perinatal mortality and predictors of neonatal survival were determined by multinomial logistic regression analyses.

Results

The overall number of pregnancies that continued after diagnosis of a severe fetal anomaly was 2266 (6.6%). The diagnoses were categorized into life‐limiting conditions (34.2%), serious disability anomaly (40.8%), potential intellectual disability (8.6%), other conditions (8.8%), and failure to classify (7.4%). During the study period, there was a significant increase in the number of women who continued pregnancy after their fetus was diagnosed with a life‐limiting condition (p= 0.03), and a decrease when the fetus was diagnosed with potential intellectual disability (p= 0.01). Pregnancy outcomes were intrauterine fetal death (17.4%), neonatal mortality (22.3%), neonatal survival (52.7%), or unknown (7.5%). Multinomial logistic regression analysis suggested an increased likelihood of neonatal survival among fetuses diagnosed with serious disability anomaly [59.8%, relative risk (RR) 4.1, 95%CI3.1–5.7], potential intellectual disability (74.4%,RR11.5, 95%CI6.2–21.2), and other conditions (80%,RR12.6, 95%CI5.7–27.9) compared with life‐limiting conditions (30.1%).

Conclusions

An increasing proportion of women chose to continue pregnancy after the fetus was diagnosed with a potentially life‐limiting condition; survival of children with these diagnoses is not uncommon.
Aflibercept vs. Ranibizumab: cost‐effectiveness of treatment for wet age‐related macular degeneration in Sweden
Authors: Panchmatia Hemangi R. , Clements Karen M. , Hulbert Erin , Eriksson Marianne , Wittrup‐Jensen Kim , Nilsson Jonas , Weinstein Milton C.
Published: April 2016

Purpose

Monthly dosing with ranibizumab (RBZ) is needed to achieve maximal visual gains in patients with neovascular (‘wet’) age‐related macular degeneration (wAMD). In Sweden, dosing is performed as needed (RBZ PRN), resulting in suboptimal efficacy. Intravitreal aflibercept (IVT‐AFL) every 2 months after three initial monthly doses was clinically equivalent to RBZ monthly dosing (RBZ q4) in wAMD clinical trials. We assessed the cost‐effectiveness of IVT‐AFL versus RBZ q4 and RBZ PRN in Sweden.

Methods

A Markov model compared IVT‐AFL to RBZ q4 or RBZ PRN over 2 years. Health states were based on visual acuity in better‐seeing eye; a proportion discontinued treatment monthly or upon visual acuity <20/400. Parameters were estimated from trial data, published literature or expert opinion. Analyses were performed from a societal perspective with a lifetime horizon. The model calculated costs, quality‐adjusted life years (QALYs) and incremental cost‐effectiveness ratios (ICERs), discounted 3% annually. Deterministic and probabilistic sensitivity analyses were performed.

Results

Lifetime cost of IVT‐AFL was 578 400 SEK, compared with 565 700 SEK for RBZ PRN and 686 600 SEK for RBZ q4. Compared with RBZ PRN, the ICER of IVT‐AFL was 27 000 SEK/QALY gained. RBZ q4 cost 20.4 million SEK/QALY gained versus IVT‐AFL. Results were sensitive to IVT‐AFL efficacy, but IVT‐AFL had a 100% probability of being cost‐effective versus both RBZ PRN and RBZ q4 at a willingness‐to‐pay threshold of 500 000 SEK.

Conclusion

Results suggest, in Sweden, at parity price level, IVT‐AFL is less costly than RBZ q4, while demonstrating similar efficacy; IVT‐AFL is cost‐effective versus RBZ PRN.
What colour are newborns' eyes? Prevalence of iris colour in the Newborn Eye Screening Test (NEST) study
Authors: Ludwig Cassie A. , Callaway Natalia F. , Fredrick Douglas R. , Blumenkranz Mark S. , Moshfeghi Darius M.
Published: April 2016

Purpose

This study aims to assess the birth prevalence of iris colour among newborns in a prospective, healthy, full‐term newborn cohort.

Methods

The Newborn Eye Screening Test (NEST) study is a prospective cohort study conducted at Lucile Packard Children's Hospital at Stanford University School of Medicine. A paediatric vitreoretinal specialist (DMM) reviewed images sent to the Byers Eye Institute telemedicine reading centre and recorded eye colour for every infant screened. Variables were graphed to assess for normality, and frequencies per subject were reported for eye colour, sex, ethnicity and race.

Results

Among 192 subjects screened in the first year of the NEST study with external images of appropriate quality for visualization of the irides, the birth prevalence of iris colour was 63.0% brown, 20.8% blue, 5.7% green/hazel, 9.9% indeterminate and 0.5% partial heterochromia. The study population was derived from a quaternary care children's hospital. We report the birth prevalence of iris colour among full‐term newborns in a diverse prospective cohort.

Conclusion

The study demonstrates a broad range of iris colour prevalence at birth with a predominance of brown iris coloration. Future studies with the NEST cohort will assess the change in iris colour over time and whether the frequencies of eye colour change as the child ages.
The outcomes of scleral buckling versus re‐vitrectomy for the treatment of recurrent inferior retinal detachment in silicone oil tamponade eyes
Authors: Wei Yong , Wu Guoji , Xu Kui , Wang Jianzhou , Zu Zhongqiao , Wang Rui
Published: April 2016

Purpose

In this retrospective study we evaluated the anatomic outcomes of scleral buckling (SB) versus re‐vitrectomy for the treatment of recurrent inferior retinal detachment (RD) in silicone oil (SiO) tamponade eyes after primary vitrectomy.

Methods

There were 103 patients (103 eyes) enrolled in this study. All patients had recurrent inferior RD in the SiO‐filled eyes within 6 months after the primary vitrectomy, and were treated by either SB or re‐vitrectomy. Patients were divided into two groups based on different surgical procedures: the SB group (49 eyes) and the re‐vitrectomy group (54 eyes). Anatomic reattachment of the retina was measured after reoperation. Based on different retinal proliferation states in different postoperative periods after primary vitrectomy, we also compared the anatomic outcomes of the two surgical procedures in two specific postoperative periods, early period (≤1 month) and late period (1–6 months).

Results

The SB and re‐vitrectomy groups exhibited similar retinal reattachment rate (65.3% versus 72.2%, p = 0.449) after reoperation. In the re‐vitrectomy group, the retinal reattachment rate was similar in the early period and the late period (70.8% versus 73.3%, p = 0.839). However, the retinal reattachment rate was significantly higher in the early period than that of the late period (80.8% versus 47.8%, p = 0.016) in the SB group. In the early surgery groups, the retinal reattachment rate was similar in the SB group compared to the re‐vitrectomy group (80.8% versus 70.8%, p = 0.411). While in the late surgery groups, retinal reattachment rate was trended higher in the re‐vitrectomy group compared to the SB group (73.3% versus 47.8%, p = 0.058).

Conclusion

For recurrent inferior RD in SO‐filled eyes, SB surgery provides similar therapeutic effectiveness with satisfactory anatomic outcomes compared to the re‐vitrectomy. For eyes with recurrent inferior RD in the early period (≤1 month) after primary vitrectomy, SB surgery may be a better choice since it causes less complication; while in the late period (1–6 months) after primary vitrectomy, re‐vitrectomy may be recommended, especially for the eyes with severe anterior proliferative vitreoretinopathy and retinal foreshortening.
Trends in penetrating and anterior lamellar corneal grafting techniques for keratoconus: a national registry study
Authors: Godefrooij Daniel A. , Gans Renze , Imhof Saskia M. , Wisse Robert P.L.
Published: April 2016

Purpose

Keratoconus is a progressive disorder and one of the primary indications for corneal transplantation. Anterior lamellar keratoplasty offers several advantages over other techniques, including endothelial preservation and longer graft survival. In this study, we examined the recent trend of using lamellar techniques for keratoconus at a national level.

Methods

Data were obtained from the Dutch national organ transplant database regarding corneal transplants for keratoconus performed in 2005 through 2014. Baseline characteristics for patients undergoing various techniques were obtained, and temporal trends were analysed.

Results

A total of 1041 operations were performed, including 736 penetrating keratoplasties (PKPs) and 297 anterior lamellar keratoplasties (ALKs). The mean age of the total surgical group was 37.4 ± 13.4 years, and 68% of patients were male (p = 0.0001). Preoperative patient characteristics were reported in all 1041 cases. The relative proportion of ALKs increased from 2005 (19% of cases) to 2010 (39% of cases) and remained approximately 30–40% thereafter. Descemet baring or deep anterior lamellar keratoplasty (DALK) was increasingly applied and was the predominant anterior lamellar technique performed from 2009 onwards.

Conclusions

The number of corneal transplantations performed annually for keratoconus decreased during the past 10 years. Lamellar techniques were increasingly performed, accounting for approximately 35% of keratoplasties in 2010 and thereafter. Among ALK techniques, maximal depth DALK is the most prevalent keratoplasty performed for keratoconus in most recent years. Penetrating keratoplasty (PKP) is still common, with a stable frequency from 2010 onwards.
Effects of peptide ratios in nanofibre‐based hydrogels for the prevention of capsular opacification
Authors: Nibourg Lisanne M. , Gelens Edith , Nibourg Simone A. F. , de Jong Menno R. , Kuijer Roel , van Kooten Theo G. , Koopmans Steven A.
Published: April 2016

Purpose

To moderate the capsular opacification (CO) response after lens surgery, an experimental study was performed in which nanofibre‐based hydrogels (nanogels) with different ratios of attached peptides were applied to provide extracellular matrix‐related cues for lens epithelial cells (LECs) in a porcine eye model.

Methods

The lens content was removed, and the capsules were refilled with nanogel. Lenses were divided into two groups, the first group (n = 34) was refilled with nanogels containing different ratios of two laminin‐derived peptides (IKVAV + YIGSR), and the latter group (n = 26) was refilled with nanogel combinations of a fibronectin‐derived and a type IV collagen‐derived peptide (RGDS + DGEA). Two lenses were refilled with culture medium to investigate the effect of the medium on LECs. After refilling, lenses were extracted and cultured for 3 weeks. Lens epithelial cells (LECs) were assessed for morphology and alpha‐smooth muscle actin (αSMA) expression using confocal laser scanning microscopy.

Results

Differences were seen in cell morphology between lenses refilled with nanogels with IKVAV + YIGSR and RGDS + DGEA peptides. In nanogels with IKVAV + YIGSR peptides, differences in LEC morphology were largest when ratios between the peptides were unequal, whereas LEC responses from the RGDS + DGEA refilled groups showed variation in LEC morphology dependent on the total quantity of mixed‐in peptides. The culture medium did not induce proliferation or transformation of LECs.

Conclusions

Ratios and concentrations of cell adhesion‐mediating peptides both can direct the LEC response, depending on the adhesion molecules of origin, by influencing LEC proliferation and transformation. Nanogels with incorporated peptides may be tuned towards CO prevention.
Autism spectrum disorders before diagnosis: results from routine developmental surveillance at 18 months
Authors: Carlsson Lotta Höglund , Westerlund Joakim , Olsson Martina Barnevik , Eriksson Mats A. , Hedvall Åsa , Gillberg Christopher , Fernell Elisabeth
Published: April 2016

Aim

This study investigated the results from the national, routine 18‐month developmental surveillance at Child Healthcare Centres (CHCs) on children later diagnosed with autism spectrum disorder (ASD).

Methods

Child Healthcare Centre records of 175 children, diagnosed with ASD before 4.5 years in Stockholm County, Sweden, were reviewed regarding the results of the eight‐item neurodevelopmental surveillance. Results were contrasted with normative data from the general child population in Stockholm County.

Results

More than one‐third of the total ASD group, including half of the group with ASD and intellectual disability (ID), did not pass the required number of items, compared to one in 50 in the general child population. Of those with ASD and ID who had passed, more than one‐third experienced developmental regression after 18 months of age. If the CHC surveillance had considered reported regulatory problems – crying, feeding and sleeping – then another 10% of the children with ASD and ID could have been identified during this surveillance.

Conclusion

The existing CHC surveillance traced half of the group of children who were later diagnosed with ASD combined with intellectual disability. Adding an item on regulatory problems to the 18‐month surveillance would have increased this number by another 10%.
Spine ultrasounds should not be routinely performed for patients with simple sacral dimples
Authors: Albert Gregory W.
Published: April 2016

Primary care providers commonly obtain spine ultrasounds for neonates with simple sacral dimples due to perceived concerns about underlying spinal dysraphism, despite a lack of scientific evidence. Nine papers addressing routine spine ultrasounds for children with sacral dimples showed that 3.4% of the 5166 patients had abnormal spine ultrasounds, compared with the 4.8% reported by another study for children without sacral dimples. Most of the abnormal findings in patients with sacral dimples were of no clinical significance.

Conclusion

Sacral dimples do not predict underlying spinal cord malformations, and spine ultrasounds should not be performed for neonates with simple sacral dimples.
Single‐centre study reports a 84% five‐year overall survival rate for paediatric solid tumours
Authors: Teppo Eero , Penttinen Jarkko , Myöhänen Outi , Vettenranta Kim , Lohi Olli
Published: April 2016

Aim

We investigated the characteristics and outcome of paediatric patients with solid tumours diagnosed and treated at the Tampere University Hospital, one of the five tertiary referral centres in Finland, for children and adolescents with malignancies.

Methods

This retrospective cohort study collected data from hospital medical records on survival, diagnosis, age, sex, tumour size and stage at diagnosis. We also observed the disease recurrence and use of autologous haematopoietic stem cell transplantation. Data analyses were carried out with the Kaplan–Meier method, various nonparametric and parametric tests, and Cox regression modelling.

Results

Between 1987 and May 2015, 424 children (59% boys), with a median age of 6.4 (IQR 2.5–11.8) years at diagnosis, were diagnosed and followed up for a median of 7.5 (range 0‐27.9) years. Central nervous system (CNS) tumours were the most common (38%), followed by lymphomas (19%), soft tissue sarcomas (10%), renal tumours (9%) and neuroblastomas (9%). The five‐year overall survival rate of all solid tumour patients was 84% (95% CI, 81–88%), 82% (95% CI, 76–89%) for CNS and 85% (95% CI, 80‐90%) for non‐CNS tumours. Advanced tumour stage at diagnosis predicted a poor prognosis.

Conclusion

The treatment results in our study are comparable with those previously published. A comprehensive local database allows for a timely follow‐up of the characteristics and quality of treatment of childhood malignancies.
Breath‐holding spells occur disproportionately more often in children with transient erythroblastopenia
Authors: Hellström Schmidt Sanna , Tedgård Ulf , Pronk Cornelis J.H.
Published: April 2016

Aim

This study aimed to evaluate the concomitant occurrence and possible association of breath‐holding spells (BHS) and transient erythroblastopenia of childhood (TEC).

Methods

This population‐based cohort study, carried out in Southern Sweden from 2004 to 2014, included patients with BHS and/or anaemia, including TEC. The subjects were evaluated for the presence of all three conditions and the diagnostic workups, disease characteristics and outcome were analysed.

Results

We studied 443 470 children under the age of 10 years during 2004–2014. The total cohort included 321 patients (0.07%) with BHS and 366 patients with a selection of anaemia diagnoses, including 41 with TEC. We found that nine (2.5%) of the 366 patients with anaemia diagnoses also had BHS and that five (12.2%) of the 41 patients with TEC also had BHS. Treatment for anaemia resolved BHS in a number of patients.

Conclusion

Our population‐based analysis revealed an overrepresentation of BHS among children with TEC, and we identified five patients with concomitant TEC and BHS. We found that correcting anaemia was an effective means of ameliorating potentially debilitating BHS and that the presence of concomitant BHS and TEC was more common than previously assumed.
The YvqE two‐component system controls biofilm formation and acid production in Streptococcus pyogenes
Authors: Isaka Masanori , Tatsuno Ichiro , Maeyama Jun‐Ichi , Matsui Hideyuki , Zhang Yan , Hasegawa Tadao
Published: April 2016

In Streptococcus pyogenes, proteins involved in determining virulence are controlled by stand‐alone response regulators and by two‐component regulatory systems. Previous studies reported that, compared to the parental strain, the yvqE sensor knockout strain showed significantly reduced growth and lower virulence. To determine the function of YvqE, we performed biofilm analysis and pH assays on yvqE mutants, and site‐directed mutagenesis of YvqE. The yvqE deletion mutant showed a slower acid production rate, indicating that YvqE regulates acid production from sugar fermentation. The mutant strain, in which the Asp26 residue in YvqE was replaced with Asn, affected biofilm formation, suggesting that this amino acid senses hydrogen ions produced by fermentative sugar metabolism. Signals received by YvqE were directly or indirectly responsible for inducing pilus expression. This study shows that at low environmental pH, biofilm formation in S. pyogenes is mediated by YvqE and suggests that regulation of pilus expression by environmental acidification could be directly under the control of YvqE.
Utilisation of surgical fundoplication for patients with gastro‐oesophageal reflux disease in the USA has declined rapidly between 2009 and 2013
Authors: Khan F. , Maradey‐Romero C. , Ganocy S. , Frazier R. , Fass R.
Published: April 2016

Background

Surgical fundoplication has been considered to be one of the leading therapeutic modalities for gastro‐oesophageal reflux disease (GERD) during the last several decades.

Aim

To determine the trend of surgical fundoplication utilisation in GERD patients during the last decade in the United States.

Methods

Population‐based study using a large nationwide database, the Explorys database system, to identify patients diagnosed with GERD and those who underwent surgical fundoplication. Using a quadratic regression model, we determined and compared the trends of surgical fundoplication utilisation annually from 2004 to 2013.

Results

We identified 4 059 060 patients with the diagnosis of GERD, of whom 2343 (0.05%) underwent surgical fundoplication between 2004 and 2013. There was a significant decline in the number of surgical fundoplications performed over the last 5 years from 0.062% in 2009 to 0.047% in 2013 (P < 0.05). Female patients accounted for the majority of those who underwent fundoplication (62.52%). Caucasian patients between the ages of 18 and 65 years were the most likely group to undergo surgical fundoplication (66.28%). The number of overweight patients undergoing surgical fundoplication has been significantly increasing over the last decade (P < 0.05). Importantly, 80% of surgical patients were treated with a proton pump inhibitor (PPI) post surgical fundoplication by 2013 (P < 0.001).

Conclusions

Utilisation of surgical fundoplication in GERD patients has been steadily declining over the past 5 years. The vast majority of patients will resume PPI treatment after surgical fundoplication.
Predicting outcome in acute severe ulcerative colitis: comparison of the Travis and Ho scores using UK IBD audit data
Authors: Lynch R. W. , Churchhouse A. M. D. , Protheroe A. , Arnott I. D. R. ,   the UK IBD Audit Steering Group
Published: April 2016

Background

Acute severe ulcerative colitis is categorised using the Truelove & Witts criteria. The Travis and the Ho scores are calculated following 72 h of steroid treatment to identify patients at risk of failing steroid therapy who require colectomy or second‐line medical therapy.

Aim

To compare the Travis and the Ho scores in a large unselected cohort to determine which might be more clinically relevant.

Methods

We analysed 3049 patients with ulcerative colitis from the 2010 round of the UK IBD audit of which 984 had acute severe ulcerative colitis. 420 patients had sufficient data for analysis. Patients were allocated into either a Travis high‐ or low‐risk group and either a Ho high‐, intermediate‐ or low‐risk group. We assessed whether further medical or surgical intervention and outcomes varied between groups.

Results

High‐risk patients in Travis and the Ho groups, when compared to lower risk groups, were more likely to fail steroid therapy: 64.5% (131/203) vs. 38.7% (84/217) (P < 0.0001) for Travis and 66.2% (96/145) vs. 46.7% (85/182) vs. 36.6% (34/93) (P < 0.0001) for Ho. They were also more likely to undergo surgery 34.0% (69/203) vs. 9.7% (21/217) for Travis and 33.1% (48/145) vs. 17.0% (31/182) vs. 11.8% (11/93) (P < 0.0001) for Ho. Travis high patients were more likely to be refractory to second‐line medical therapy: 44.6% (37/83) vs. 20.0% (9/45) (P = 0.01).

Conclusions

Patients identified as high risk using the Travis or the Ho scoring systems are more likely to be resistant to IV steroids and require surgery. Risk of surgery in both high‐risk populations is lower than previously reported.
Usage patterns of paracetamol in France
Authors: Duong Mai , Gulmez Sinem Ezgi , Salvo Francesco , Abouelfath Abdelilah , Lassalle Régis , Droz Cécile , Blin Patrick , Moore Nicholas
Published: April 2016

Aims

The aim of the present study was to describe the real‐life usage patterns of paracetamol.

Methods

The Echantillon Généraliste de Bénéficiaires (EGB) database, the permanent 1/97 representative sample from the French national healthcare insurance system, was searched in 2011 to identify usage patterns, concomitant chronic diseases and use of cardiovascular medication in users prescribed single‐ingredient (SP) and combination (CP) paracetamol, representing 85% of all sales.

Results

Of 526 108 subjects aged ≥15 years in the EGB, 268 725 (51%) had paracetamol dispensed on ≥1 occasion; of these, 207 707 (77%) were dispensed only SP and 61 018 (23%) received CP with or without SP. SP users were younger (48.3 years vs. 50.5 years), and 57% of SP users vs. 58% of CP users were female. Chronic comorbidities were more common in CP than SP users. SP users had, on average, 3.4 dispensings per year vs. 5.0 for CP users, for 36 defined daily doses (DDD, 3 g) of SP vs. 53 DDD per year for CP; 49% SP users bought 14 DDD or fewer; 15% bought >60 DDD. Use of paracetamol increased with age from about 16 DDD per year in 15–30‐year‐olds to over 90 DDD per year in patients above the age of 75; 53% of patients ≤60 years bought fewer than 14 DDD per year, whereas 55% of those >60 bought more than 30 DDD per year. More than half the dispensings exceeded the legal per‐box limit of 8 g.

Conclusions

Over 50% of the French adult population were dispensed paracetamol at least once over the course of a year, generally for short‐term use. Considering recent misgivings on the real efficacy and safety of paracetamol, such widespread use might have important public health consequences.
Quantifying rigidity of Parkinson's disease in relation to laxative treatment: a service evaluation
Authors: Augustin Aisha D. , Charlett André , Weller Clive , Dobbs Sylvia M. , Taylor David , Bjarnason Ingvar , Dobbs R. John
Published: April 2016

Aim

To estimate whether laxatives prescribed for constipation in Parkinson's disease (PD) could moderate rigidity. Constipation predates diagnosis of PD by decades. Deposition of misfolded protein may begin in the gut, driven by dysbiosis. Successive antimicrobial exposures are associated with cumulative increase in rigidity, and rigidity has biological gradients on circulating leukocyte‐subset counts.

Methods

Retrospective service evaluation, in a gut/brain axis clinic, yielded an interrupted time series, relating maintenance laxative and other medication to rigidity, in consecutive outpatients identified by inclusion and exclusion criteria. Objective assessment of rigidity was used to bring greater sensitivity to change, validated against subjective gold standard (UPDRS).

Results

There were 1493 measurements of torque required to extend (flexor rigidity) and flex (extensor rigidity) the forearm in 79 PD patients over 374 person‐years. Both were strongly associated with UPDRS (P < 0.001 and P = 0.008, respectively). Before exhibition of laxative, flexor rigidity increased by 6% (95% CI 1, 10) per year, plateauing at −2% (−4, 1) per year after, with no shift at initiation. Change in slope was significant (P = 0.002), and manifest in those naïve to antiparkinsonian medication. The change was replicated for individual laxative classes (bulk, osmotic, enterokinetic). There was no temporal change in extensor rigidity. Limited experience with a quanylate cyclase‐C receptor agonist (17 patients, 6 person‐years) indicated a large and significant step down in flexor and extensor rigidity, of 19% (1, 34) and 16% (6, 24) respectively (P = 0.04 and <0.001).

Conclusions

Maintenance laxative usage was associated with apparent stemming of the temporal increase in rigidity in PD, adding to indicative evidence of a continuing role of gastrointestinal dysbiosis in pathogenesis.
Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi‐Modal Multi‐Tissue Human Experimental Model – An Explorative Study
Authors: Nielsen Lecia Møller , Olesen Anne Estrup , Sato Hiroe , Christrup Lona Louring , Drewes Asbjørn Mohr
Published: April 2016

The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol‐O‐methyltransferase (COMT) gene on pain sensitivity in healthy participants was investigated. Catechol‐O‐methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi‐modal and multi‐tissue experimental pain model in 40 healthy participants aged 20–65. Seventeen different single nucleotide polymorphisms in different genes (OPRM, OPRK, OPRD and COMT) were included in the analysis. Experimental pain tests included thermal skin stimulation, mechanical muscle and bone stimulation and mechanical, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non‐carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p < 0.015). Additionally, carriers of the C allele (CC/CT) of OPRK rs6473799 reported a 30.4% higher mechanical visceral pain tolerance threshold than non‐carriers (TT; p < 0.019). For the other polymorphisms and stimulations, no associations were found (all p > 0.05). In conclusion, COMT rs4680 and OPRK rs6473799 polymorphisms seem to be associated with pain sensitivity. Thus, the findings support a possible genetic influence on pain sensitivity.
Confidence Sets for Optimal Factor Levels of a Response Surface
Authors: Wan Fang , Liu Wei , Bretz Frank , Han Yang
Published: April 2016

Construction of confidence sets for the optimal factor levels is an important topic in response surfaces methodology. In Wan et al. (2015), an exact confidence set has been provided for a maximum or minimum point (i.e., an optimal factor level) of a univariate polynomial function in a given interval. In this article, the method has been extended to construct an exact confidence set for the optimal factor levels of response surfaces. The construction method is readily applied to many parametric and semiparametric regression models involving a quadratic function. A conservative confidence set has been provided as an intermediate step in the construction of the exact confidence set. Two examples are given to illustrate the application of the confidence sets. The comparison between confidence sets indicates that our exact confidence set is better than the only other confidence set available in the statistical literature that guarantees the confidence level.
Approximate Median Regression for Complex Survey Data with Skewed Response
Authors: Fraser Raphael André , Lipsitz Stuart R. , Sinha Debajyoti , Fitzmaurice Garrett M. , Pan Yi
Published: April 2016

The ready availability of public-use data from various large national complex surveys has immense potential for the assessment of population characteristics using regression models. Complex surveys can be used to identify risk factors for important diseases such as cancer. Existing statistical methods based on estimating equations and/or utilizing resampling methods are often not valid with survey data due to complex survey design features. That is, stratification, multistage sampling, and weighting. In this article, we accommodate these design features in the analysis of highly skewed response variables arising from large complex surveys. Specifically, we propose a double-transform-both-sides (DTBS)'based estimating equations approach to estimate the median regression parameters of the highly skewed response; the DTBS approach applies the same Box–Cox type transformation twice to both the outcome and regression function. The usual sandwich variance estimate can be used in our approach, whereas a resampling approach would be needed for a pseudo-likelihood based on minimizing absolute deviations (MAD). Furthermore, the approach is relatively robust to the true underlying distribution, and has much smaller mean square error than a MAD approach. The method is motivated by an analysis of laboratory data on urinary iodine (UI) concentration from the National Health and Nutrition Examination Survey.
Bayesian Hierarchical Modeling for Subject-Level Response Classification in Peptide Microarray Immunoassays
Authors: Imholte Gregory , Gottardo Raphael
Published: April 2016

The peptide microarray immunoassay simultaneously screens sample serum against thousands of peptides, determining the presence of antibodies bound to array probes. Peptide microarrays tiling immunogenic regions of pathogens (e.g., envelope proteins of a virus) are an important high throughput tool for querying and mapping antibody binding. Because of the assay's many steps, from probe synthesis to incubation, peptide microarray data can be noisy with extreme outliers. In addition, subjects may produce different antibody profiles in response to an identical vaccine stimulus or infection, due to variability among subjects’ immune systems. We present a robust Bayesian hierarchical model for peptide microarray experiments, pepBayes, to estimate the probability of antibody response for each subject/peptide combination. Heavy-tailed error distributions accommodate outliers and extreme responses, and tailored random effect terms automatically incorporate technical effects prevalent in the assay. We apply our model to two vaccine trial data sets to demonstrate model performance. Our approach enjoys high sensitivity and specificity when detecting vaccine induced antibody responses. A simulation study shows an adaptive thresholding classification method has appropriate false discovery rate control with high sensitivity, and receiver operating characteristics generated on vaccine trial data suggest that pepBayes clearly separates responses from non-responses.
Variable Selection for Binary Spatial Regression: Penalized Quasi-Likelihood Approach
Authors: Feng Wenning , Sarkar Abdhi , Lim Chae Young , Maiti Tapabrata
Published: April 2016

We consider the problem of selecting covariates in a spatial regression model when the response is binary. Penalized likelihood-based approach is proved to be effective for both variable selection and estimation simultaneously. In the context of a spatially dependent binary variable, an uniquely interpretable likelihood is not available, rather a quasi-likelihood might be more suitable. We develop a penalized quasi-likelihood with spatial dependence for simultaneous variable selection and parameter estimation along with an efficient computational algorithm. The theoretical properties including asymptotic normality and consistency are studied under increasing domain asymptotics framework. An extensive simulation study is conducted to validate the methodology. Real data examples are provided for illustration and applicability. Although theoretical justification has not been made, we also investigate empirical performance of the proposed penalized quasi-likelihood approach for spatial count data to explore suitability of this method to a general exponential family of distributions.
Single-Index Varying Coefficient Model for Functional Responses
Authors: Luo Xinchao , Zhu Lixing , Zhu Hongtu
Published: April 2016

Recently, massive functional data have been widely collected over space across a set of grid points in various imaging studies. It is interesting to correlate functional data with various clinical variables, such as age and gender, in order to address scientific questions of interest. The aim of this article is to develop a single-index varying coefficient (SIVC) model for establishing a varying association between functional responses (e.g., image) and a set of covariates. It enjoys several unique features of both varying-coefficient and single-index models. An estimation procedure is developed to estimate varying coefficient functions, the index function, and the covariance function of individual functions. The optimal integration of information across different grid points is systematically delineated and the asymptotic properties (e.g., consistency and convergence rate) of all estimators are examined. Simulation studies are conducted to assess the finite-sample performance of the proposed estimation procedure. Furthermore, our real data analysis of a white matter tract dataset obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study confirms the advantage and accuracy of SIVC model over the popular varying coefficient model.
Internet‐based cognitive behaviour therapy and physical exercise – Effects studied by automated telephone assessments in mental ill‐health patients; a randomized controlled trial
Authors: Strid Catharina , Andersson Claes , Forsell Yvonne , Öjehagen Agneta , Lundh Lars‐Gunnar
Published: April 2016

Objectives

Mental ill‐health has become a large health problem and it is important for caregivers to provide effective treatment alternatives. REGASSA is a randomized controlled study performed in primary care to study the effects of 12 weeks of Internet‐based cognitive behaviour therapy (ICBT) and physical exercise (PE) compared with treatment as usual (TAU) in patients with mild‐to‐moderate mental ill‐health. The present study aimed to examine the results of these treatment alternatives on psychological functioning, stress, and sleep disturbances.

Methods

The study comprised 879 patients with mental ill‐health taking part in the REGASSA study. Data were collected by Interactive Voice Response (IVR), a computerized, automated telephone technique. The treatments were compared at baseline, twice during treatment, at the end of treatment and at three follow‐ups after treatment. Measures used were the Outcome Questionnaire‐45, the short versions of the Perceived Stress Scale, and the Karolinska Sleep Questionnaire.

Results

Linear mixed models showed that the patients in ICBT and PE had better results than in TAU on psychological functioning and sleep disturbances, p < .001, with weak‐to‐moderate effect sizes. On stress there were no differences; all groups made improvements. Women had stronger effects than men. More patients recovered on psychological functioning (OQ‐45) in ICBT and PE than in TAU.

Conclusions

Internet‐based cognitive behaviour therapy and PE proved to be effective treatment alternatives for patients with mild‐to‐moderate mental ill‐health in improving psychological functioning, stress, and sleep disturbances and could be useful alternatives in primary care.

Practitioner points

Internet‐based cognitive behaviour therapy and physical exercise proved to be effective treatment alternatives for mental ill‐health patients in primary care.

Automated techniques (Interactive Voice Response) could be useful for following treatment course in large groups of patients in the health care.

It is important to use measures that capture different aspects of patients’ health problems.

The recruitment of participants was based on patients’ interest and inclusion criteria which may have affect the generalizability.