bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of wheat homeodomain-leucine zipper family genes and functional analysis of TaHDZ5-6A in drought tolerance in transgenic Arabidopsis
Authors: Li Shumin , Chen Nan , Li Fangfang , Mei Fangming , Wang Zhongxue , Cheng Xinxiu , Kang Zhensheng , Mao Hude
Published: January 2020

Background

Many studies inArabidopsisand rice have demonstrated that HD-Zip transcription factors play important roles in plant development and responses to abiotic stresses. Although common wheat (Triticum aestivumL.) is one of the most widely cultivated and consumed food crops in the world, the function of the HD-Zip proteins in wheat is still largely unknown.

Results

To explore the potential biological functions ofHD-Zipgenes in wheat, we performed a bioinformatics and gene expression analysis of the HD-Zip family. We identified 113 HD-Zip members from wheat and classified them into four subfamilies (I-IV) based on phylogenic analysis against proteins fromArabidopsis, rice, and maize. MostHD-Zipgenes are represented by two to three homeoalleles in wheat, which are named asTaHDZX_ZA,TaHDZX_ZB, orTaHDZX_ZD, where X denotes the gene number and Z the wheat chromosome on which it is located.TaHDZsin the same subfamily have similar protein motifs and intron/exon structures. The expression profiles ofTaHDZgenes were analysed in different tissues, at different stages of vegetative growth, during seed development, and under drought stress. We found that mostTaHDZgenes, especially those in subfamilies I and II, were induced by drought stress, suggesting the potential importance of subfamily I and IITaHDZmembers in the responses to abiotic stress. Compared with wild-type (WT) plants, transgenicArabidopsisplants overexpressingTaHDZ5-6Adisplayed enhanced drought tolerance, lower water loss rates, higher survival rates, and higher proline content under drought conditions. Additionally, the transcriptome analysis identified a number of differentially expressed genes between35S::TaHDZ5-6Atransgenic and wild-type plants, many of which are involved in stress response.

Conclusions

Our results will facilitate further functional analysis of wheatHD-Zipgenes, and also indicate thatTaHDZ5-6Amay participate in regulating the plant response to drought stress. Our experiments show thatTaHDZ5-6Aholds great potential for genetic improvement of abiotic stress tolerance in crops.
A randomized controlled trial evaluating the impact of selective axillary nerve block after arthroscopic subacromial decompression
Authors: Rothe Christian , Lund Jørgen , Jenstrup Morten Troels , Steen-Hansen Christian , Lundstrøm Lars Hyldborg , Andreasen Asger Mølgaard , Lange Kai Henrik Wiborg
Published: January 2020

Background

The sensory innervation of the shoulder is complex and there are variations in the branching patterns of the sensory fibres. Articular branches from the axillary nerve to the subacromial bursa are described in more than 50% of investigated shoulders but the isolated contribution of sensory input from the axillary nerve has never been investigated clinically.

We hypothesized that a selective block of the axillary nerve would reduce morphine consumption and pain after arthroscopic subacromial decompression.

Methods

We included 60 patients in a randomized, blinded, placebo-controlled study. Patients were randomized to a preoperative selective ultrasound-guided axillary nerve block with 20 mL ropivacaine (7.5 mg/mL) or 20 mL saline. Primary outcome was intravenous morphine consumption 0–4 h postoperatively. Secondary outcome was postoperative pain evaluated by a visual analogue scale (VAS) score (0–100).

Results

We analysed data from 50 patients and found no significant difference in 0–4 h postoperative morphine consumption between the two groups (ropivacaine 14 mg, placebo 18 mg (P = 0.12)). There was a reduction in postoperative pain: VAS 0–4 h (area under the curve) (ropivacaine 135, placebo 182 (P = 0.03)), VAS after 8 h (ropivacaine 9, placebo 20 (P = 0.01)) and VAS after 24 h (ropivacaine 7, placebo 18 (P = 0.04)). Eight out of 19 patients with a successful selective axillary nerve block needed an interscalene brachial plexus escape block.

Conclusions

Selective block of the axillary nerve has some pain relieving effect, but in this setting the effect was unpredictable, variable and far from sufficient in a large proportion of the patients.

Trial registration

ClinicalTrials.gov (NCT01463865). Registered: November 1, 2011.
Selenium, copper, zinc and hypertension: an analysis of the National Health and Nutrition Examination Survey (2011–2016)
Authors: Bastola Mrigendra M. , Locatis Craig , Maisiak Richard , Fontelo Paul
Published: January 2020

Background

Hypertension is a major cardiovascular illness worldwide with many underlying causes. The role of trace elements selenium, copper, and zinc in hypertension is uncertain. The objective of this study was to evaluate the role of these trace elements in hypertension.

Method

Data from 6683 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2016 were analyzed using Statistical Analytical System (SAS, version 9.4) software for the role of trace elements in hypertension in age range 8 to 80 years, irrespective of the antihypertensive medication taken. Recent American Heart Association guidelines and pediatric practice guidelines for hypertension were used.

Results

Findings showed a significant positive association between serum selenium levels and hypertension but not serum zinc and copper. At optimal levels for transport and distribution, serum selenium levels of 120 μg/L or higher (reference level 70–150 μg/L) were significantly associated with hypertension (OR = 1.46, 95% CI = 1.29–1.66) after adjusting for confounding factors. At serum selenium level greater than 150 μg/L, the association with hypertension strengthened (OR = 1.69, 95% CI = 1.32–2.17).

Conclusion

A positive association was found between serum selenium and hypertension, irrespective of age or anti-hypertensive medications intake. These findings also suggest that the reference levels of serum levels in healthy individuals may need to be re-determined, if supported by additional studies. If validated, patients with hypertension may also need to be cautioned about selenium intake.
Regional differences in reasons for consultation and general practitioners’ spectrum of services in northern Germany – results of a cross-sectional observational study
Authors: Schäfer Ingmar , Hansen Heike , Ruppel Thomas , Lühmann Dagmar , Wagner Hans-Otto , Kazek Agata , Scherer Martin
Published: January 2020

Background

Among other factors, the patients’ consultation reasons and GPs’ spectrum of services determine the process and outcome of the medical treatment. So far, however, there has been little information on differences in reasons for consultation and GPs’ services between urban and rural areas. Our study’s goal was thus to investigate these factors in relation to the regional location of GPs’ practices.

Methods

We conducted a cross-sectional observational study based on standardised GP interviews in a quota sampling design. All counties and independent cities within a radius of 120 km around Hamburg were divided into three regional categories (urban area, environs, rural area) and stratified proportionally to the population size. Differences in the number of reasons for consultation and services were analysed by multivariate linear regressions in mixed models adjusted for random effects on the levels of the German federal states and administrative districts. Differences in individual consultation reasons and services were identified by logistic regression via stepwise forward and backward selection.

Results

Primary care practices in 34 of the 37 selected administrative districts (91.9%) were represented in the dataset. In total, 211 GPs were personally interviewed. On average, GPs saw 344 patients per month with a slightly higher number of patients in rural areas. They reported 59.1 ± 15.4 different reasons for consultation and 30.3 ± 3.9 different services. There was no statistically significant regional variation in the number of different consultation reasons, but there was a broader service spectrum by rural GPs (ß = − 1.42; 95% confidence interval − 2.75/− 0.08; p = 0.038) which was statistically explained by a higher level of medical training. Additionally, there were differences in the frequency of individual consultation reasons and services between rural and urban areas.

Conclusion

GPs in rural areas performed more frequently services usually provided by medical specialists in urban areas. This might be caused by a low availability of specialists in rural areas. The association between medical training and service spectrum might imply that GPs compensate the specific needs of their patients by completing advanced medical training before or after setting up a medical practice.

Trial registration

The study was registered in ClinicalTrials.gov (NCT02558322).
Prevention and management of diarrhea associated with naldemedine among patients receiving opioids: a retrospective cohort study
Authors: Takagi Yusuke , Osawa Gakuji , Kato Yoriko , Ikezawa Eri , Kobayashi Chika , Aruga Etsuko
Published: January 2020

Background

Naldemedine, a novel peripherally-acting mu-opioid receptor antagonist, has improved opioid-induced constipation in randomized controlled trials. The most frequent adverse event of naldemedine is diarrhea, which can cause abdominal pain and often leads to treatment discontinuation. We aimed to identify risk factors and appropriate management strategies for key adverse events including diarrhea associated with naldemedine, since those have not been extensively studied.

Methods

We conducted a multi-center retrospective cohort study. Eligible patients had cancer, had undergone palliative care at participating centers, had been prescribed regular opioids, and had taken at least one dose of naldemedine between June 2017 and March 2018. The primary endpoint was the incidence of diarrhea according to baseline characteristics. Secondary endpoints included the duration of naldemedine administration, daily defecation counts before and after starting naldemedine, duration and severity of diarrhea as an adverse event of naldemedine, other adverse events, and the incidence of constipation within 7 days after recovery from diarrhea. We defined patients who started naldemedine within three days of starting a regularly prescribed opioid as the early group, and the remainder as the late group.

Results

Among 103 patients who received naldemedine, 98 fulfilled the eligibility criteria. The median age was 68 years and 48% of the patients were female. Median performance status was 3, and the median oral intake was 50%. The median duration of naldemedine administration and overall survival were 25 and 64 days, respectively. The incidence of diarrhea in the early group (n = 26) was significantly lower than in the late group (n = 72) (3.9% vs. 22.2%, p = 0.02). Daily defecation counts increased after late (median 0.43 to 0.88, p < 0.001), but remained stable after early naldemedine administration (median 1.00 to 1.00, p = 0.34). Constipation after the diarrhea was resolved was common (53%), especially among patients who stopped naldemedine (78%). The diarrhea was improved within three days in 92% of patients who stopped other laxatives.

Conclusions

The early administration of naldemedine is beneficial because it reduces adverse events including diarrhea. Diarrhea caused by naldemedine can be effectively managed by stopping other laxatives while continuing naldemedine.
Safety of endoscopic procedures with monopolar versus bipolar instruments in an ex vivo porcine model
Authors: Shinmura Kensuke , Ikematsu Hiroaki , Kojima Motohiro , Nakamura Hiroshi , Osera Shozo , Yoda Yusuke , Hori Keisuke , Oono Yasuhiro , Ochiai Atsushi , Yano Tomonori
Published: January 2020

Background

Monopolar instruments are generally used in colorectal endoscopic mucosal resection (EMR). Bipolar instruments have previously been reported to be as safe as monopolar instruments. We sought to compare the safety of the monopolar and bipolar snare and hemostatic forceps in an animal model.

Methods

We created 5-mm, 10-mm, and 15-mm target lesions on an ex vivo porcine rectum. Two lesions of each size were resected via monopolar polypectomy (M-P), monopolar EMR (M-E), bipolar polypectomy (B-P), and bipolar EMR (B-E). We performed a pathological evaluation of the conditions of perforation and the effects of burning on the tissues. In addition, we burned the muscularis propria covered with submucosal layer using monopolar and bipolar hemostatic forceps and performed pathological evaluations.

Results

Polypectomy and EMR were performed in a total of 24 target lesions. A perforation was found on histology in one case of M-P and one case of M-E after removing target lesions of 15 mm in diameter. There were no perforations during endoscopic resection using the bipolar snare. The thermal denaturation in B-P did not reach the muscularis propria layer regardless of the size of the target lesion. Although thermal damage after using monopolar hemostatic forceps was extensive, thermal denaturation was only seen on the surface of the submucosal layer when bipolar hemostatic forceps were used.

Conclusions

Bipolar instruments cause less damage to the tissue than monopolar instruments. Our results also suggest that bipolar instruments may be safer than monopolar instruments in endoscopic procedures for colorectal lesions.
The effects of promoting oral intake using the Kuchi-kara Taberu index, a comprehensive feeding assistant tool, in older pneumonia patients: a cluster randomized controlled trial
Authors: Shamoto Hiroshi , Koyama Tamami , Momosaki Ryo , Maeda Keisuke , Wakabayashi Hidetaka
Published: January 2020

Background

The multidisciplinary comprehensive care (MDCC) program promotes the improvement of oral intake for older patients. The Kuchi-kara Taberu (ingesting orally in Japanese, KT) index was developed to objectively assess patient conditions in the MDCC program. This trial examined the effects of the index in promoting oral intake in older patients with pneumonia.

Methods

A cluster randomized controlled trial was conducted in 10 local hospitals targeting older patients with pneumonia (≥65 years). Ten hospitals were allocated randomly to either the intervention or the control group. Both groups (each with five hospitals) received the MDCC program for oral feeding, which consisted of professional assessment, care, and treatment. The KT index was used by the intervention group, focusing on improving low score items. The primary outcome was determined using the Functional Oral Intake Scale (FOIS) at discharge or 1 month after admission.

Results

One hundred and twelve patients (46 women and 66 men) who participated from 10 hospitals, with a median age of 88 years (interquartile range [IQR], 80–91), were examined. The median FOIS level and the number of patients with oral intake (FOIS ≥ level 4) at discharge were 4 (IQR, 4–6) and 89 (79.5%), respectively. The duration of nil per os was 2 (IQR, 1–5) days. Clusters were not matched in the presence of Kuchi-kara Taberu Shiawase-wo Mamoru-kai-certified medical staff promoting oral intake in patients with dysphagia in each hospital. The median FOIS levels of 53 patients in the intervention group and 59 patients in the control group were 5 (IQR, 4–6) and 4 (IQR, 4–5), respectively, showing no statistically significant difference (P = 0.76). According to a multivariate analysis, the KT index had no positive effect on FOIS levels.

Conclusions

This trial was not able to demonstrate the usefulness of the KT index due to random assignment failure. However, both the intervention and control groups showed a high prevalence of oral intake (FOIS ≥ level 4) at discharge.

Trial registration

UMIN-Clinical Trial Registry, UMIN000025172, December 17, 2016.
Identification of subclinical tuberculosis in household contacts using exposure scores and contact investigations
Authors: Bekken Gry Klouman , Ritz Christian , Selvam Sumithra , Jesuraj Nelson , Hesseling Anneke C. , Doherty T. Mark , Grewal Harleen M. S. , Vaz Mario , Jenum Synne
Published: January 2020

Background

The goal of tuberculosis elimination put forward in the End TB Strategy prioritizes diagnosis and treatment of incipient and subclinical TB, recently defined by key stakeholders as “asymptomatic, early pre-clinical disease during which pathology evolves”. Regarded as indicative of a high risk of TB progression, considerable efforts have been made to identify these cases through exploration of biomarkers. The present study aimed to evaluate simple scoring systems for TB exposure as screening tools for subclinical TB, the only identifiable of the incipient and subclinical disease states, in a contact investigation (CI) setting of low HIV-prevalence.

Methods

Nested within a large prospective study in household contacts (HHCs) of smear positive pulmonary TB cases in South-India conducted 2010–2012, we assessed 1) the association between the Tuberculosis Contact Score (TCS) and the Infectivity Score, with established tools for Mycobacterium tuberculosis (Mtb) infection, corrected for established TB risk factors, and 2) the capability of the TB exposure scores to identify subclinical TB defined by Mtb-culture positivity in sputum or gastric aspirate (subjects < 5 years) specimen.

Results

Of 525 HHCs, 29 were Mtb-culture positive and 96.6% of these asymptomatic. The TCS and the Infectivity Score associated with positive Tuberculin Skin Test and QuantiFeron TB-Gold In-tube assay (QFT) results in multivariate analyses (TCS: ORTST 1.16, 95% CI: 1.01, 1.33; ORQFT 1.33 95% CI: 1.16, 1.51. Infectivity Score: ORTST 1.39, 95% CI: 1.10, 1.76; ORQFT 1.41 95% CI: 1.16, 1.71). The Infectivity Score showed a moderate capability to identify subclinical TB (AUC of 0.61, 95% CI: 0.52, 0.70).

Conclusions

Although our results did not identify an easily applicable screening tool for subclinical TB, the present study indicates that focusing on TB-related symptoms in CI settings may be of limited value for early identification of HHCs with high risk for TB progression.
Ambulatory screening and decontamination to prevent Staphylococcus aureus complications in patients undergoing elective surgery (STAUfrei): study protocol for a controlled intervention study
Authors: Bauer Antonia , Grünewald Martin , Eberhardt Hans , Schulz Rieke , Martus Peter , Brüggenjürgen Bernd , Joos Stefanie , Sturm Heidrun
Published: January 2020

Background

Surgical site infections (SSI) are the most common health care associated infections in German acute hospitals and can result in prolonged hospital stays, increased use of antibiotics and utilisation of care. Staphylococcus aureus bacteria (methicillin-resistant S Aureus (MRSA) and methicillin-susceptible S Aureus (MSSA)) are amongst the most prominent causes of SSI. While up to 90% of documented S Aureus colonization is already detectable prior to hospital admission, the majority of hygiene measures in Germany is focused on the hospital setting. It is hypothesized that early detection and decontamination of S Aureus colonization in primary care can prevent health care associated infections and reduce the number of S Aureus isolates in the hospital setting.

Methods

This study is a controlled interventional study (N = 13,260) with a pre-post comparison. The intersectoral intervention (over 2 years) will encompass the following elements: ambulatory detection and decontamination of MRSA and MSSA prior to elective surgery combined with a structured follow-up care. Patients from the control group will be screened in the hospital setting, in accordance with the standard operating procedure (SOP) in routine care. The primary endpoint is the reduction of MRSA and MSSA colonization upon hospital admission. Secondary endpoints are complication rate (SSI), length of stay, recolonization of patients (3 and 6 months after release), patient and provider satisfaction, patient compliance and cost development.

Discussion

In case of positive results, the chance of a widespread uptake and implementation in routine care are considered high. The active involvement of primary care providers in the implementation of screening and decontamination as well as follow-up care is a unique feature of this study. The positive resonance of primary care providers during the recruitment phase highlights the relevance of the topic to the participating actors. These efforts are coupled with patient education and specifically trained medical staff, promising a sustained impact. The STAUfrei care pathway can homogenize current practices in routine care and provide a template for further intersectoral cooperation.

Trial registration

German Clinical Trials Register (DRKS), DRKS00016615. Registered on April 1st, 2019.
Retraction Note: The epidemiology and chemotherapeutic approaches to the control of urinary schistosomiasis in school-age children (SAC): a systematic review
Authors: Atalabi Tolulope Ebenezer , Adubi Taiwo Oluwakemi
Published: January 2020

The authors have retracted this article [1] because of methodological inaccuracies and incorrect use of the PRISMA/PROSPERO guidelines of systematic reviews and meta-analyses in the article.
Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome
Authors: Caffarelli Carla , Gonnelli Stefano , Pitinca Maria Dea Tomai , Camarri Silvia , Al Refaie Antonella , Hayek Joussef , Nuti Ranuccio
Published: January 2020

Background

More than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. The disorder is caused by mutations in a single gene and the disease severity in affected individuals can be quite variable. Specific MECP2 mutations may lead phenotypic variability and different degrees of disease severity. It is known that low bone mass is a frequent and early complication of subjects with Rett syndrome. As a consequence of the low bone mass Rett girls are at an increased risk of fragility fractures. This study aimed to investigate if specific MECP2 mutations may affects the degree of involvement of the bone status in Rett subjects.

Methods

In 232 women with Rett syndrome (mean age 13.8 ± 8.3 yrs) we measured bone mineral density at whole body and at femur (BMD-FN and BMD-TH) by using a DXA machine (Hologic QDR 4500). QUS parameters were assessed at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). Moreover, ambulation capacity (independent or assisted), fracture history and presence of scoliosis were assessed. We divided the subjects with the most common point mutations in two group based on genotype-phenotype severity; in particular, there has been consensus in recognising that the mutations R106T, R168X, R255X, R270X are considered more severe.

Results

As aspect, BMD-WB, BMD-FN and BMD-TH were lower in subjects with Rett syndrome that present the most severe mutations with respect to subjects with Rett syndrome with less severe mutations, but the difference was statistically significant only for BMD-FN and BMD-TH (p < 0.05). Also both AD-SoS and BTT values were lower in subjects that present the most severe mutations with respect to less severe mutations but the difference was not statistically significant. Moreover, subjects with Rett syndrome with more severe mutations present a higher prevalence of scoliosis (p < 0.05) and of inability to walk (p < 0.05).

Conclusion

This study confirms that MECP2 mutation type is a strong predictor of disease severity in subjects with Rett syndrome. In particular, the subjects with more severe mutation present a greater deterioration of bone status, and a higher prevalence of scoliosis and inability to walk.
Association of reduced inner retinal thicknesses with chronic kidney disease
Authors: Paterson Euan N. , Ravindran Meera L. , Griffiths Kayleigh , Le Velly Claire A. , Cardwell Chris C. , McCarter Rachel V. , Nicol Patrick , Chhablani Jay K. , Rasheed Mohammed Abdul , Vupparaboina Kiran Kumar , MacGillivray Thomas J. , Harbinson Mark , Maxwell Alexander P. , Hogg Ruth E. , McKay Gareth J.
Published: January 2020

Background

Tissue derived biomarkers may offer utility as indicators of accumulated damage. Reduced thickness of retinal neuronal tissue and the vascular choroid have previously been associated with vascular damage and diabetes. We evaluated associations between retinal thickness, retinal microvascular and choroidal measures, and renal function in a population with a high burden of comorbidity.

Methods

Participants were recruited from nuclear cardiology or renal medicine clinics. Retinal and choroidal thickness were measured from spectral-domain optical coherence tomograms. Retinal microvascular parameters were assessed from digital fundus photographs using a semi-automated software package. Main Outcome Measure: Chronic kidney disease (CKD) categorised as: CKD stages 1–2, eGFR ≥60 ml/min/1.73m2; CKD stage 3, eGFR 30–59 ml/min/1.73m2, and CKD stages 4–5, eGFR ≤29 ml/min/1.73m2.

Results

Participants (n = 241) had a mean age of 65 years and a mean eGFR of 66.9 ml/min/1.73m2. Thirty–nine % of the cohort had diabetes and 27% were using diuretics. Thinning of the inner retina and changes to its microvascular blood supply were associated with lower eGFR and CKD stages 4 and 5, while no associations were found between the outer retinal layers or their choroidal blood supply and CKD of any stage. These associations remained following adjustment for age, mean arterial blood pressure, diabetes status, low-density lipoprotein, body mass index, and sex.

Conclusions

Inner retinal thinning and retinal microvascular variation is associated with advanced CKD (stages 4 & 5) independent of important confounding factors, but not with earlier stage CKD (stage 3) and, therefore, its utility as a biomarker for early CKD is not supported in this study.
Urgent start peritoneal dialysis: are we there yet?
Authors: Greenberg Keiko I. , Jaar Bernard G.
Published: January 2020

The use of peritoneal dialysis (PD) has increased substantially in the United States (US) in the past decade. This was likely spurred in large part by the implementation of the expanded prospective payment system for the Medicare End Stage Renal Disease (ESRD) program in 2011. Over the same period, there has also been growing interest in urgent start PD, which is commonly defined as initiation of PD within 14 days of catheter insertion. Ye and colleagues recently reported their experience with urgent start PD in 2059 Chinese ESRD patients over a 9-year period. Rates of complications, including peri-catheter leaks and peritonitis, were very low despite initiation of PD immediately after open catheter placement via open laparotomy in nearly all patients. Long term technique survival was good, with only 75 patients developing catheter failure. This study provides further evidence to suggest that urgent start PD is feasible and effective, although the generalizability of these results to Western populations is unclear. Recent proposed changes to the payment models in the Medicare ESRD program, designed to incentivize use of kidney transplantation and home dialysis, are likely to further propel growth of PD and urgent start PD in the US. Further studies are needed to optimize use of urgent PD and patient outcomes.
Protocol of a randomized open label multicentre trial comparing continuous intrajejunal levodopa infusion with deep brain stimulation in Parkinson’s disease - the INfusion VErsus STimulation (INVEST) study
Authors: van Poppelen D. , Sisodia V. , de Haan R. J. , Dijkgraaf M. G. W. , Schuurman P. R. , Geurtsen G. J. , Berk A. E. M. , de Bie R. M. A. , Dijk J. M.
Published: January 2020

Background

Both Deep Brain Stimulation (DBS) and Continuous intrajejunal Levodopa Infusion (CLI) are effective therapies for the treatment of Parkinson’s disease (PD). To our knowledge, no direct head-to-head comparison of DBS and CLI has been performed, whilst the costs probably differ significantly. In the INfusion VErsus STimulation (INVEST) study, costs and effectiveness of DBS and CLI are compared in a randomized controlled trial (RCT) in patients with PD, to study whether higher costs of one of the therapies are justified by superiority of that treatment.

Methods

A prospective open label multicentre RCT is being performed, with ancillary patient preference observational arms. Patients with PD who, despite optimal pharmacological treatment, have severe response fluctuations, bradykinesia, dyskinesias, or painful dystonia are eligible for inclusion. A total of 66 patients will be randomized. There is no minimal inclusion in the patient preference arms. The primary health economic outcomes are costs per unit on the Parkinson’s Disease Questionnaire-39 (PDQ-39) and costs per unit Quality-Adjusted Life Year (QALY) at 12 months. The main clinical outcome is patient-reported quality of life measured with the PDQ-39 at 12 months. Patients will additionally be followed during 36 months after initiation of the study treatment.

Discussion

The INVEST trial directly compares the costs and effectiveness of the advanced therapies DBS and CLI.

Trial registration

Dutch Trial Register identifier 4753, registered November 3rd, 2014; EudraCT number 2014–001501-32, Clinicaltrials.gov: NCT02480803.
TRAAP2 - TRAnexamic Acid for Preventing postpartum hemorrhage after cesarean delivery: a multicenter randomized, doubleblind, placebo- controlled trial – a study protocol
Authors:   On behalf of the TRAAP2 Study Group and the Groupe de Recherche en Obstétrique et Gynécologie (GROG), Sentilhes Loïc , Daniel Valérie , Deneux-Tharaux Catherine
Published: January 2020

Background

An antifibrinolytic agent that blocks lysine-binding sites on plasminogen molecules, tranexamic acid reduces bleeding-related mortality in women with postpartum hemorrhage (PPH), especially administered fairly soon after delivery. According to the randomized controlled trials thus far reported for PPH prevention after cesarean deliveries (n = 16), women who received tranexamic acid had significantly less postpartum blood loss and no increase in severe adverse effects. These were, however, primarily small single-center studies that had fundamental methodological flaws. Multicenter randomized controlled trials with adequate power are necessary to demonstrate its value persuasively before tranexamic acid goes into widespread use for the prevention of PPH after cesarean deliveries.

Methods/design

This study will be a multicenter, double-blind, randomized controlled trial with two parallel groups including 4524 women with cesarean deliveries before or during labor, at a term ≥34 weeks, modeled on our previous study of tranexamic acid administered after vaginal deliveries. Treatment (either tranexamic acid 1 g or placebo) will be administered intravenously just after birth. All women will also receive a prophylactic uterotonic agent. The primary outcome will be the incidence of PPH, defined by a calculated estimated blood loss > 1000 mL or a red blood cell transfusion before day 2 postpartum. This study will have 80% power to show a 20% reduction in the incidence of PPH, from 15.0 to 12.0%.

Discussion

As an, inexpensive, easy to administer drug that can be add to the routine management of cesarean births in delivery rooms, tranexamic acid is a promising candidate for preventing PPH after these births. This large, adequately powered, multicenter randomized placebo-controlled trial seeks to determine if the benefits of the routine prophylactic use of tranexamic acid after cesarean delivery significantly outweigh its risks.

Trial registration

ClinicalTrials.gov NCT03431805 (February 12, 2018).
Caesarean section rates from Malaysian tertiary hospitals using Robson’s 10-group classification
Authors: Karalasingam Shamala Devi , Jeganathan Ravichandran , Jegasothy Ravindran , Reidpath Daniel D.
Published: January 2020

Background

Rising caesarean section rates is a concern worldwide. This study aimed to use Robson’s ten group classification to identify which groups of women were contributing most to the rising caesarean section rates in Malaysian tertiary hospitals and to compare between hospitals, using a common standard set of variables.

Methods

A 5-year (2011–2015) cross-sectional study was conducted using data from the Malaysian National Obstetrics Registry (NOR). A total of 608,747 deliveries were recorded from 11 tertiary state hospitals and 1 tertiary hospital from the Federal territory.

Results

During the study period, there were 141,257 Caesarean sections (23.2%). Caesarean sections in Group 1 (nulliparous term pregnancy in spontaneous labour) and Group 3 (multiparous term pregnancy in spontaneous labour) had an increasing trend from 2011 to 2015. The group that contributed most to the overall caesarean section rates was Group 5 (multiparous, singleton, cephalic≥37 weeks with previous caesarean section) and the rates remained high during the 5-year study period. Groups 6, 7 and 9 had the highest caesarean section rates but they made the smallest contribution to the overall rates.

Conclusions

Like many countries, the rate of caesarean section has risen over time, and the rise is driven by caesarean section in low-risk groups. There was an important hospital to hospital variation. The rise in caesarean section rates reflects a globally disturbing trend, and changes in policy and training that creates a uniform standard across hospitals should be considered.
Gestational diabetes and the human salivary microbiota: a longitudinal study during pregnancy and postpartum
Authors: Crusell Mie K. W. , Brink Lærke R. , Nielsen Trine , Allin Kristine H. , Hansen Torben , Damm Peter , Lauenborg Jeannet , Hansen Tue H. , Pedersen Oluf
Published: January 2020

Background

An aberrant composition of the salivary microbiota has been found in individuals with type 2 diabetes, and in pregnant women salivary microbiota composition has been associated with preeclampsia and pre-term birth. Pregnant women, who develop gestational diabetes (GDM), have a high risk of developing type 2 diabetes after pregnancy. In the present study we assessed whether GDM is linked to variation in the oral microbial community by examining the diversity and composition of the salivary microbiota.

Method

In this observational study the salivary microbiota of pregnant women with GDM (n = 50) and normal glucose regulation (n = 160) in third trimester and 9 months postpartum was assessed by 16S rRNA gene amplicon sequencing of the V1-V3 region. GDM was diagnosed in accordance with the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Cross-sectional difference in alpha diversity was assessed using Student’s t-test and longitudinal changes were assessed by mixed linear regression. Cross-sectional and longitudinal difference in beta diversity was assessed by permutational multivariate analyses of variance. Differentially abundant genera and OTUs were identified by negative binomial regression.

Results

In the third trimester, two species-level operational taxonomic units (OTUs), while eight OTUs postpartum were differentially abundant in women with GDM compared with normoglycaemic women. OTU richness, Shannon diversity and Pielou evenness decreased from late pregnancy to 9 months after delivery regardless of glycaemic status.

Conclusion

GDM is associated with a minor aberration of the salivary microbiota during late pregnancy and postpartum. For unknown reasons richness of the salivary microbiota decreased from late pregnancy to postpartum, which might be explained by the physiological changes of the immune system during human pregnancy.
Transverse versus vertical skin incision for planned cesarean hysterectomy: does it matter?
Authors: Szlachta-McGinn Alec , Mei Jenny , Tabsh Khalil , Afshar Yalda
Published: January 2020

Background

To investigate differences in perioperative outcomes by type of skin incision, transverse versus vertical, for planned cesarean hysterectomy for placenta accreta spectrum (PAS).

Methods

A retrospective cohort study of all women who underwent a planned cesarean hysterectomy for abnormal placentation at a single academic medical center over 5 years. The Student’s t-test was used for continuous variables and Fisher’s exact test compared categorical variables. Continuous data were presented as median and compared using the Wilcoxon-rank sum test.

Results

Forty-two planned cesarean hysterectomies were identified. A transverse skin incision was made in 43% (n = 18); a vertical skin incision was made in 57% (n = 24). Skin incision was independent of BMI (30.3 vs 30.8 kg/m2, p = 0.37), placental location (p = 0.82), and PAS-subtype (p = 0.26). Mean estimated blood loss (EBL) was 2.73 l (L) (range 0.5–20) and was not significantly different between transverse and vertical skin incision (2.6 L vs 2.8 L, p = 0.8). There was significantly shorter operative time with transverse skin incision (180 vs 238 min, p = 0.03), with no difference in intraoperative complications, including cystotomy (p = 0.22) and ureteral injury (p = 0.73). Postoperatively, there was no difference in maternal length of stay (4.8 vs 4.4 days, p = 0.74) or post-operative opioid use (117 vs 180 morphine equivalents, p = 0.31).

Conclusion

Transverse skin incision is associated with shorter operative time for patients undergoing planned cesarean hysterectomy. There was no difference in EBL, intraoperative complications, postoperative length of stay, or opioid use. Given an increasing rate of cesarean hysterectomy, we should consider variables that optimize maternal outcomes and resource utilization.
Implementing a healthy postpartum lifestyle after gestational diabetes or preeclampsia: a qualitative study of the partner’s role
Authors: Almli Ingfrid , Haugdahl Hege S. , Sandsæter Heidi L. , Rich-Edwards Janet W. , Horn Julie
Published: January 2020

Background

Women with preeclampsia (PE) and gestational diabetes mellitus (GDM) are at increased risk for later cardiovascular disease, and lifestyle measures are recommended to prevent subsequent disease. Partner support has been shown to be important in lifestyle modification in other diseases, but there is a lack of knowledge of partner involvement in PE and GDM. The aim of this study was to explore the partner’s experiences and knowledge of gestational diseases, and how the partner wishes to contribute to lifestyle change.

Methods

A qualitative study with one focus group interview and seven in-depth individual interviews, involving eleven partners of women with a pregnancy complicated by GDM or PE. The interview data were inductively analysed using four-step systematic text condensation, supported by interdependence theory.

Results

Partners experienced a strong “we-feeling” and wanted to support the woman in lifestyle changes. At the same time, they felt insecure, worried, foolish and left out and they missed information from clinicians. The partners felt that their involvement was crucial to lasting lifestyle changes and expected that the clinicians would routinely invite them to discuss lifestyle change.

Conclusions

Partners considered themselves an important resource for lifestyle changes for women with PE and GDM, but missed being more directly invited, informed and included in maternity care and wanted to participate in the care that followed the gestational disease. This study can help health professionals to realize that partners are an overlooked resource that can make important contributions to improve the health of the whole family if they are involved and supported by health services.
PDAC-ANN: an artificial neural network to predict pancreatic ductal adenocarcinoma based on gene expression
Authors: Almeida Palloma Porto , Cardoso Cristina Padre , de Freitas Leandro Martins
Published: January 2020

Background

Although the pancreatic ductal adenocarcinoma (PDAC) presents high mortality and metastatic potential, there is a lack of effective therapies and a low survival rate for this disease. This PDAC scenario urges new strategies for diagnosis, drug targets, and treatment.

Methods

We performed a gene expression microarray meta-analysis of the tumor against normal tissues in order to identify differentially expressed genes (DEG) shared among all datasets, named core-genes (CG). We confirmed the CG protein expression in pancreatic tissue through The Human Protein Atlas. It was selected five genes with the highest area under the curve (AUC) among these proteins with expression confirmed in the tumor group to train an artificial neural network (ANN) to classify samples.

Results

This microarray included 461 tumor and 187 normal samples. We identified a CG composed of 40 genes, 39 upregulated, and one downregulated. The upregulated CG included proteins and extracellular matrix receptors linked to actin cytoskeleton reorganization. With the Human Protein Atlas, we verified that fourteen genes of the CG are translated, with high or medium expression in most of the pancreatic tumor samples. To train our ANN, we selected the best genes (AHNAK2, KRT19, LAMB3, LAMC2, and S100P) to classify the samples based on AUC using mRNA expression. The network classified tumor samples with an f1-score of 0.83 for the normal samples and 0.88 for the PDAC samples, with an average of 0.86. The PDAC-ANN could classify the test samples with a sensitivity of 87.6 and specificity of 83.1.

Conclusion

The gene expression meta-analysis and confirmation of the protein expression allow us to select five genes highly expressed PDAC samples. We could build a python script to classify the samples based on RNA expression. This software can be useful in the PDAC diagnosis.
MammaPrint guides treatment decisions in breast Cancer: results of the IMPACt trial
Authors: Soliman Hatem , Shah Varsha , Srkalovic Gordan , Mahtani Reshma , Levine Ellis , Mavromatis Blanche , Srinivasiah Jayanthi , Kassar Mohamad , Gabordi Robert , Qamar Rubina , Untch Sarah , Kling Heather M. , Treece Tina , Audeh William
Published: January 2020

Background

Increased usage of genomic risk assessment assays suggests increased reliance on data provided by these assays to guide therapy decisions. The current study aimed to assess the change in treatment decision and physician confidence based on the 70-gene risk of recurrence signature (70-GS, MammaPrint) and the 80-gene molecular subtype signature (80-GS, BluePrint) in early stage breast cancer patients.

Methods

IMPACt, a prospective, case-only study, enrolled 452 patients between November 2015 and August 2017. The primary objective population included 358 patients with stage I-II, hormone receptor-positive, HER2-negative breast cancer. The recommended treatment plan and physician confidence were captured before and after receiving results for 70-GS and 80-GS. Treatment was started after obtaining results. The distribution of 70-GS High Risk (HR) and Low Risk (LR) patients was evaluated, in addition to the distribution of 80-GS compared to IHC status.

Results

The 70-GS classified 62.5% (n = 224/358) of patients as LR and 37.5% (n = 134/358) as HR. Treatment decisions were changed for 24.0% (n = 86/358) of patients after receiving 70-GS and 80-GS results. Of the LR patients initially prescribed CT, 71.0% (44/62) had CT removed from their treatment recommendation. Of the HR patients not initially prescribed CT, 65.1% (41/63) had CT added. After receiving 70-GS results, CT was included in 83.6% (n = 112/134) of 70-GS HR patient treatment plans, and 91.5% (n = 205/224) of 70-GS LR patient treatment plans did not include CT. For patients who disagreed with the treatment recommended by their physicians, most (94.1%, n = 16/17) elected not to receive CT when it was recommended. For patients whose physician-recommended treatment plan was discordant with 70-GS results, discordance was significantly associated with age and lymph node status.

Conclusions

The IMPACt trial showed that treatment plans were 88.5% (n = 317/358) in agreement with 70-GS results, indicating that physicians make treatment decisions in clinical practice based on the 70-GS result. In clinically high risk, 70-GS Low Risk patients, there was a 60.0% reduction in treatment recommendations that include CT. Additionally, physicians reported having greater confidence in treatment decisions for their patients in 72% (n = 258/358) of cases after receiving 70-GS results.

Trial registration

“Measuring the Impact of MammaPrint on Adjuvant and Neoadjuvant Treatment in Breast Cancer Patients: A Prospective Registry” (NCT02670577) retrospectively registered on Jan 27, 2016.
Incidence of biomarkers in high-grade gliomas and their impact on survival in a diverse SouthEast Asian cohort - a population-based study
Authors: Ang Samantha Ya Lyn , Lee Lester , See Angela An Qi , Ang Ting Yao , Ang Beng Ti , King Nicolas Kon Kam
Published: January 2020

Background

Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population.

Methods

Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients’ age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test.

Results

181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006).

Conclusions

The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.