bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of ultrasensitive quantitative-PCR to assess the impact of primaquine on asymptomatic relapse of Plasmodium vivax infections: a randomized, controlled trial in Lao PDR
Authors: Phommasone Koukeo , van Leth Frank , Imwong Mallika , Henriques Gisela , Pongvongsa Tiengkham , Adhikari Bipin , Peto Thomas J. , Promnarate Cholrawee , Dhorda Mehul , Sirithiranont Pasathorn , Mukaka Mavuto , Peerawaranun Pimnara , Day Nicholas P. J. , Cobelens Frank , Dondorp Arjen M. , Newton Paul N. , White Nicholas J. , von Seidlein Lorenz , Mayxay Mayfong 
Published: January 2020

Abstract
Background
Trials to assess the efficacy of the radical cure of Plasmodium vivax malaria with 8-aminoquinolines require that most post-treatment relapses are identified, but there is no consensus on the optimal duration of follow-up in either symptomatic or asymptomatic vivax malaria. The efficacy of a 14-day course of primaquine on the cumulative incidence of recurrent asymptomatic P. vivax infections detected by ultrasensitive quantitative PCR (uPCR) as a primary endpoint was assessed.

Methods
A randomized, placebo-controlled, single-blind trial was conducted in four villages of the Lao PDR during 2016–2018 nested in a larger project evaluating mass drug administrations (MDA) with dihydroartemisinin-piperaquine (DP) and a single low-dose primaquine to clear Plasmodium falciparum infections. In the nested sub-study, eligible participants with mono- or mixed P. vivax infections detected by uPCR were randomized to receive either 14 days of primaquine (0.5 mg/kg/day) or placebo during the last round of MDA (round 3) through directly observed therapy. Participants were checked monthly for 12 months for parasitaemia using uPCR. The primary outcome was cumulative incidence of participants with at least one recurrent episode of P. vivax infection.

Results
20 G6PD-normal participants were randomized in each arm. 5 (29%) of 20 participants in the placebo arm experienced asymptomatic, recurrent P. vivax infections, resulting in a cumulative incidence at month 12 of 29%. None of the 20 participants in the intervention arm had recurrent infections (p = 0.047 Fisher’s exact test). Participants with recurrent P. vivax infections were found to be parasitaemic for between one and five sequential monthly tests. The median time to recurrence of P. vivax parasitaemia was 178 days (range 62–243 days).

Conclusions
A 14-day course of primaquine in addition to a DP-MDA was safe, well-tolerated, and prevented recurrent asymptomatic P. vivax infections. Long follow-up for up to 12 months is required to capture all recurrences following the treatment of asymptomatic vivax infection. To eliminate all malarias in settings where P. vivax is endemic, a full-course of an 8-aminoquinolines should be added to MDA to eliminate all malarias.
Trial registration This study was registered with ClinicalTrials.gov under NCT02802813 on 16th June 2016. https://clinicaltrials.gov/ct2/show/NCT02802813
Relationship between disease activity status or clinical response and patient-reported outcomes in patients with non-radiographic axial spondyloarthritis: 104-week results from the randomized controlled EMBARK study
Authors: Dougados Maxime , van der Heijde Désirée , Tsai Wen-Chan , Saaibi Diego , Marshall Lisa , Jones Heather , Pedersen Ron , Vlahos Bonnie , Tarallo Miriam 
Published: January 2020

Abstract
Background
We assessed the external validity of composite indices Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Assessment in SpondyloArthritis international Society (ASAS) 40 response (ASAS40) by evaluating the correlations between the changes in some patient reported outcomes (PROs) for patients with non-radiographic axial spondyloarthritis (nr-axSpA) and the changes in the scores of the composite indices.

Methods
This was a post-hoc analysis of data from the EMBARK study in patients with nr-axSpA treated with etanercept. PROs were grouped according to ASDAS status (inactive [< 1.3], low [≥ 1.3 to < 2.1], high [≥ 2.1 to ≤3.5], and very high [> 3.5]), patient achievement of > 50% improvement in BASDAI (BASDAI50 responders), and > 40% improvement in ASAS (ASAS40 responders) at 104 weeks. Analyses were conducted on observed cases available at Week 104. Changes in PROs from Baseline to Week 104 were assessed using analysis of covariance with adjustment for baseline with linear contrast.

Results
Higher ASDAS disease activity at 104 weeks was associated with lower long-term improvement from baseline in PROs (e.g., total back pain [visual analog scale, cm (95% confidence interval): − 4.58 (− 4.95, − 4.21), − 3.86 (− 4.28, − 3.43), − 2.15 (− 2.68, − 1.61), and 1.30 (− 0.51, 3.12) for inactive, low, high, and very high ASDAS disease activity, respectively; Multidimensional Fatigue Inventory (MFI) general fatigue: − 4.77 (− 5.70, − 3.84), − 2.96 (− 4.04, − 1.87), − 1.00 (− 2.32, 0.31), and 2.14 (− 2.10, 6.38); all p < 0.001)]. BASDAI50 non-responders had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: − 1.61 (− 2.05, − 1.18) vs. –4.43 (− 4.69, − 4.18); MFI general fatigue: − 0.01 (− 1.12, 1.09) vs. –4.30 (− 4.98, − 3.62); all p < 0.001). ASAS40 non-responders also had less improvement in PROs from Baseline to Week 104 vs. responders (e.g., total back pain: − 1.91 (− 2.30, − 1.52) vs. –4.75 (− 5.05, − 4.46); MFI general fatigue: − 0.63 (− 1.56, 0.30) vs. –4.64 (− 5.37, − 3.91); all p < 0.001).

Conclusion
Composite indices are valid for monitoring treatment response and adequately reflect treatment-related changes experienced by patients with nr-axSpA.

Trial registration
ClinicalTrials.gov identifier: NCT01258738. Registered 9 December 2010.
Intervention Scalability Assessment Tool: A decision support tool for health policy makers and implementers
Authors: Milat Andrew , Lee Karen , Conte Kathleen , Grunseit Anne , Wolfenden Luke , van Nassau Femke , Orr Neil , Sreeram Padmaja , Bauman Adrian 
Published: January 2020

Abstract
Background
Promising health interventions tested in pilot studies will only achieve population-wide impact if they are implemented at scale across communities and health systems. Scaling up effective health interventions is vital as not doing so denies the community the most effective services and programmes. However, there remains a paucity of practical tools to assess the suitability of health interventions for scale-up. The Intervention Scalability Assessment Tool (ISAT) was developed to support policy-makers and practitioners to make systematic assessments of the suitability of health interventions for scale-up.

Methods
The ISAT was developed over three stages; the first stage involved a literature review to identify similar tools and frameworks that could be used to guide scalability assessments, and expert input to develop draft ISAT content. In the second stage, the draft ISAT tool was tested with end users. The third stage involved revising and re-testing the ISAT with end users to further refine the language and structure of the final ISAT.

Results
A variety of information and sources of evidence should be used to complete the ISAT. The ISAT consists of three parts. Part A: ‘setting the scene’ requires consideration of the context in which the intervention is being considered for scale-up and consists of five domains, as follows: (1) the problem; (2) the intervention; (3) strategic/political context; (4) evidence of effectiveness; and (5) intervention costs and benefits. Part B asks users to assess the potential implementation and scale-up requirements within five domains, namely (1) fidelity and adaptation; (2) reach and acceptability; (3) delivery setting and workforce; (4) implementation infrastructure; and (5) sustainability. Part C generates a graphical representation of the strengths and weaknesses of the readiness of the proposed intervention for scale-up. Users are also prompted for a recommendation as to whether the intervention (1) is recommended for scale-up, (2) is promising but needs further information before scaling up, or (3) does not yet merit scale-up.

Conclusion
The ISAT fills an important gap in applied scalability assessment and can become a critical decision support tool for policy-makers and practitioners when selecting health interventions for scale-up. Although the ISAT is designed to be a health policy and practitioner tool, it can also be used by researchers in the design of research to fill important evidence gaps.
Nurses' and auxiliary nurse midwives' adherence to essential birth practices with peer coaching in Uttar Pradesh, India: a secondary analysis of the BetterBirth trial
Authors: Molina Rose L. , Neal Brandon J. , Bobanski Lauren , Singh Vinay Pratap , Neville Bridget A. , Delaney Megan Marx , Lipsitz Stuart , Karlage Ami , Shetye Mrunal , Semrau Katherine E. A. 
Published: January 2020

AbstractBackgroundThe BetterBirth trial tested the effect of a peer coaching program around the WHO Safe Childbirth Checklist for birth attendants in primary-level facilities in Uttar Pradesh, India on a composite measure of perinatal and maternal mortality and maternal morbidity. This study aimed to examine the adherence to essential birth practices between two different cadres of birth attendants—nurses and auxiliary nurse midwives (ANMs)—during and after a peer coaching intervention for the WHO Safe Childbirth Checklist.MethodsThis is a secondary analysis of birth attendant characteristics, coaching visits, and behavior uptake during the BetterBirth trial through birth attendant surveys, coach observations, and independent observations. Descriptive statistics were calculated overall, and by staffing cadre (staff nurses and ANMs) for demographic characteristics. Logistic regression using the Pearson overdispersion correction (to account for clustering by site) was used to assess differences between staff nurses and ANMs in the intervention group during regular coaching (2-month time point) and 4 months after the coaching program ended (12-month time point).ResultsOf the 570 birth attendants who responded to the survey in intervention and control arms, 474 were staff nurses (83.2%) and 96 were ANMs (16.8%). In the intervention arm, more staff nurses (240/260, 92.3%) received coaching at all pause points compared to ANMs (40/53, 75.5%). At baseline, adherence to practices was similar between ANMs and staff nurses (~ 30%). Overall percent adherence to essential birth practices among ANMs and nurses was highest at 2 months after intervention initiation, when frequent coaching visits occurred (68.1% and 64.1%, respectively,p = 0.76). Practice adherence tapered to 49.2% among ANMs and 56.1% among staff nurses at 12 months, which was 4 months after coaching had ended (p = 0.68).ConclusionsOverall, ANMs and nurses responded similarly to the coaching intervention with the greatest increase in percent adherence to essential birth practices after 2 months of coaching and subsequent decrease in adherence 4 months after coaching ended. While coaching is an effective strategy to support some aspects of birth attendant competency, the structure, content, and frequency of coaching may need to be customized according to the birth attendant training and competency.Trial registrationClinicalTrials.gov:NCT2148952; Universal Trial Number: U1111–1131-5647.
Monteggia-like lesions in adults treated with radial head arthroplasty—mid-term follow-up of 27 cases
Authors: Jung Matthias , Groetzner-Schmidt Corinna , Porschke Felix , Grützner Paul A. , Guehring Thorsten , Schnetzke Marc 
Published: January 2020

Abstract
Background
The aim of the study was to analyze the functional and radiological outcome of Monteggia-like lesions in adults with unreconstructible fracture of the radial head and treatment with radial head arthroplasty.

Methods
Twenty-seven patients (mean age 56 years; range 36 to 79 years) with a Monteggia-like lesion and treatment with radial head replacement were included in this retrospective study. Minimum follow-up was 2 years. Clinical assessment included the pain level with the visual analog scale in rest (VASR) and under pressure (VASP), range of motion, Mayo Elbow Performance Score (MEPS), and Disability of the Arm, Shoulder, and Hand score (DASH). A detailed radiological evaluation was performed. Complications and revisions were also analyzed.

Results
After a mean follow-up period of 69 months (range, 24 to 170) the mean DASH score was 30 ± 24, the MEPS averaged 77 ± 20 points, the mean VASR was 2.1 ± 2.4, and VASP was 4.5 ± 3.5. Mean loss of extension was 24° ± 18 and flexion was 124° ± 20. Heterotopic ossifications were noted in 12 patients (44%). A total of 17 complications were noted in 11 patients (41%), leading to 15 revision surgeries in 9 patients (33%). Patients with a complicated postoperative course showed a worse clinical outcome compared with patients without complications measured by MEPS (68 ± 22 vs. 84 ± 16), DASH (49 ± 16 vs. 20 ± 22) and ulnohumeral motion (77° ± 31 vs. 117° ± 23).

Conclusions
Monteggia-like lesions with unreconstructible radial head fracture and treatment with radial head replacement are prone to complications and revisions.
Diagnostic studies of abortion in Danish cattle 2015–2017
Authors: Wolf-Jäckel Godelind Alma , Hansen Mette Sif , Larsen Gitte , Holm Elisabeth , Agerholm Jørgen Steen , Jensen Tim Kåre 
Published: January 2020

AbstractBackgroundAbortion is a major source of economic losses in cattle breeding. Abortion occurs due to a wide range of causes, but infections are the most frequently diagnosed. However, establishing an aetiological diagnosis remains challenging due to the large variety of bacteria, protozoa, viruses, and fungi that have been associated with abortion in cattle. Economic restraints limit the range of diagnostic methods available for routine diagnostics, and decomposition of the conceptus or lack of proper fetal and/or maternal samples further restrict the diagnostic success. In this study, we report recent diagnostic findings from bovine abortions in Denmark, a country that has a large dairy sector and is free from most infectious agents causing epizootic abortion in cattle. The aims of the study were: (i) to identify infectious causes of bovine abortion in Denmark, (ii) to categorise the diagnostic findings based on the level of diagnostic certainty, and (iii) to assess the diagnostic rate. Due to economic restraints, only a limited panel of routine diagnostic methods were available. Placentas and/or fetuses from mid- to late-term abortions and stillbirths (n = 162) were submitted to the Danish National Veterinary Institute between January 2015 and June 2017. The aborted materials were examined macroscopically, histologically, and by bacterial culture. Maternal blood samples were tested for bovine viral diarrhoea virus (BVDV) antibodies.ResultsThe likely aetiology of the abortion was diagnosed in 52 cases, resulting in a diagnostic rate of 33%. The most common cause was protozoal infection (19%) followed by infection withTrueperella pyogenes(3%),Staphylococcus aureus(2%), and non-haemolyticEscherichia coli(2%). Lesions in fetuses with a protozoal infection were consistent with neosporosis. In many cases (38%), inflammatory changes were found in the placenta and/or fetal organs but no specific aetiology was identified. Neither infection withBrucellaspp. nor maternal BVDV antibodies were detected. The majority of submitting herds (92%) were each represented by fewer than three abortion cases over the study period.ConclusionsProtozoal infection, most likely neosporosis, was the most commonly diagnosed cause of abortion and the only one associated with potential epizootic abortion events. Despite using a reduced number of diagnostic methods in comparison to other abortion studies, the diagnostic rate of this study was within the range reported in an earlier Danish study, as well as in recent international studies. The low number of submitted cases per herd and the sparse anamnestic information provided at submission hampered conclusions on the potential epizootic character of the abortion events in question.
Spontaneous trigger words associated with confirmed out-of-hospital cardiac arrest: a descriptive pilot study of emergency calls
Authors: Tamminen Joonas , Lydén Erik , Kurki Jan , Huhtala Heini , Kämäräinen Antti , Hoppu Sanna 
Published: January 2020

Abstract
Background
According to the International Liaison Committee on Resuscitation (ILCOR), the trigger words used by callers that are associated with cardiac arrest constitute a scientific knowledge gap. This study was designed to find hypothetical trigger words in emergency calls in order to improve the specificity of out-of-hospital cardiac arrest recognition.

Methods
In this descriptive pilot study conducted in a Finnish hospital district, linguistic contents of 80 emergency calls of dispatcher-suspected or EMS-encountered out-of-hospital cardiac arrests between January 1, 2017 and May 31, 2017 were analysed. Spontaneous trigger words used by callers were transcribed and grouped into 36 categories. The association between the spontaneous trigger words and confirmed true cardiac arrests was tested with logistic regression.

Results
Of the suspected cardiac arrests, 51 (64%) were confirmed as true cardiac arrests when ambulance personnel met the patient. A total of 291 spontaneous trigger words were analysed. ‘Is not breathing’ (n = 9 [18%] in the true cardiac arrest group vs n = 1 [3%] in the non-cardiac arrest group, odds ratio [OR] 6.00, 95% confidence interval [CI] 0.72–50.0), ‘the patient is blue’ (n = 9 [18%] vs n = 1 [3%], OR 6.00, 95% CI 0.72–50.0), ‘collapsed or fallen down’ (n = 12 [24%] vs n = 2 [7%], OR 4.15, 95% CI 0.86–20.1) and ‘is wheezing’ (n = 17 [33%] vs n = 5 [17%], OR 2.40, 95% CI 0.78–7.40) were frequently used to describe true cardiac arrest. ‘Is snoring’ was associated with a false suspicion of cardiac arrest (n = 1 [2%] vs n = 6 [21%], OR 0.08, 95% CI 0.009–0.67).

Conclusions
In our pilot study, no trigger word was associated with confirmed cardiac arrest. ‘Is wheezing’ was a frequently used spontaneous trigger word among later confirmed cardiac arrest victims.
Estimating dose-response for time to remission with instrumental variable adjustment: the obscuring effects of drug titration in Genome Based Therapeutic Drugs for Depression Trial (GENDEP): clinical trial data
Authors: Hellier Jennifer , Emsley Richard , Pickles Andrew 
Published: January 2020

AbstractBackgroundThreshold regression, in which time to remission is modelled as a stochastic drift towards a boundary, is an alternative to the proportional hazards survival model and has a clear conceptual mechanism for examining the effects of drug dose. However, for both threshold regression and proportional hazard models, when dose titration occurs during treatment, the estimated causal effect of dose can be biased by confounding. An instrumental variable analysis can be used to minimise such bias.MethodWeekly antidepressant dose was measured in 380 men and women with major depression treated with escitalopram or nortriptyline for 12 weeks as part of the Genome Based Therapeutic Drugs for Depression (GENDEP) study. The averaged dose relative to maximum prescribing dose was calculated from the 12 trial weeks and tested for association with time to depression remission. We combined the instrumental variable approach, utilising randomised treatment as an instrument, with threshold regression and proportional hazard survival models.ResultsThe threshold model was constructed with two linear predictors. In the naïve models, averaged daily dose was not associated with reduced time to remission. By contrast, the instrumental variable analyses showed a clear and significant relationship between increased dose and faster time to remission, threshold regression (velocity estimate: 0.878, 95% confidence interval [CI]: 0.152–1.603) and proportional hazards (log hazards ratio: 3.012, 95% CI: 0.086–5.938).ConclusionsWe demonstrate, using the GENDEP trial, the benefits of these analyses to estimate causal parameters rather than those that estimate associations. The results for the trial dataset show the link between antidepressant dose and time to depression remission. The threshold regression model more clearly distinguishes the factors associated with initial severity from those influencing treatment effect. Additionally, applying the instrumental variable estimator provides a more plausible causal estimate of drug dose on treatment effect. This validity of these results is subject to meeting the assumptions of instrumental variable analyses.Trial registrationEudraCT, 2004–001723-38; ISRCTN,03693000. Registered on 27 September 2007.
Small extracellular vesicles derived from embryonic stem cells restore ovarian function of premature ovarian failure through PI3K/AKT signaling pathway
Authors: Liu Mengyu , Qiu Yu , Xue Zhuowei , Wu Ruoyu , Li Jie , Niu Xin , Yuan Ji , Wang Yang , Wu Qingkai 
Published: January 2020

Abstract
Background
Premature ovarian failure (POF) has a great impact on reproductive endocrine function in females, and it is an important cause of infertility. Previous studies have demonstrated that small extracellular vesicles (sEVs) derived from stem cells play an important role in tissue regeneration. This study aimed to investigate the therapeutic effect of sEVs derived from embryonic stem cells (ESCs-sEVs) on damaged ovaries and explore the underlying molecular mechanisms.

Methods
Mice POF models were established by injecting mice with cyclophosphamide and busulfan. Then, ESCs-sEVs were intravenously transplanted into POF mice. The plasma of mice was harvested at 1 and 2 weeks after treatment to analyze the levels of anti-Mullerian hormone (AMH), estradiol (E2), and follicle stimulating hormone (FSH) by ELISA. The morphology of ovaries and follicles was observed by H&E staining, and apoptosis of granulosa cells was detected by TUNEL. In vitro, EdU and CCK-8 tests were used to evaluate the proliferation of cultured granulosa cells stimulated by ESCs-sEVs. Western blotting was used to determine the expression of PI3K/AKT and apoptotic-related proteins.

Results
After transplantation of ESCs-sEVs, the levels of serum sex hormones recovered to normal levels. In addition, the number of follicles was significantly increased, and the number of apoptotic cells was decreased. The results in vitro revealed that ESCs-sEVs could significantly improve the proliferation rate of granulosa cells and increase the expression of phosphorylated PI3K and AKT. Meanwhile, the positive effect on proliferation and the negative effect on apoptosis observed in granulosa cells were obviously decreased when the PI3K/AKT signaling pathway was inhibited.

Conclusion
Our findings suggested that ESCs-sEVs could improve ovarian function by regulating the PI3K/AKT signaling pathway, which could provide a promising clinical therapy for POF.