bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial and temporal distribution of infectious disease epidemics, disasters and other potential public health emergencies in the World Health Organisation Africa region, 2016–2018
Authors: TALISUNA Ambrose Otau , OKIRO Emelda Aluoch , YAHAYA Ali Ahmed , STEPHEN Mary , BONKOUNGOU Boukare , MUSA Emmanuel Onuche , MINKOULOU Etienne Magloire , OKEIBUNOR Joseph , IMPOUMA Benido , DJINGAREY Haruna Mamoudou , YAO N’da Konan Michel , OKA Sakuya , YOTI Zabulon , FALL Ibrahima Socé
Published: January 2020

Background

Emerging and re-emerging diseases with pandemic potential continue to challenge fragile health systems in Africa, creating enormous human and economic toll. To provide evidence for the investment case for public health emergency preparedness, we analysed the spatial and temporal distribution of epidemics, disasters and other potential public health emergencies in the WHO African region between 2016 and 2018.

Methods

We abstracted data from several sources, including: the WHO African Region’s weekly bulletins on epidemics and emergencies, the WHO-Disease Outbreak News (DON) and the Emergency Events Database (EM-DAT) of the Centre for Research on the Epidemiology of Disasters (CRED). Other sources were: the Program for Monitoring Emerging Diseases (ProMED) and the Global Infectious Disease and Epidemiology Network (GIDEON). We included information on the time and location of the event, the number of cases and deaths and counter-checked the different data sources.

Data analysis

We used bubble plots for temporal analysis and generated graphs and maps showing the frequency and distribution of each event. Based on the frequency of events, we categorised countries into three: Tier 1, 10 or more events, Tier 2, 5–9 events, and Tier 3, less than 5 or no event. Finally, we compared the event frequencies to a summary International Health Regulations (IHR) index generated from the IHR technical area scores of the 2018 annual reports.

Results

Over 260 events were identified between 2016 and 2018. Forty-one countries (87%) had at least one epidemic between 2016 and 2018, and 21 of them (45%) had at least one epidemic annually. Twenty-two countries (47%) had disasters/humanitarian crises. Seven countries (the epicentres) experienced over 10 events and all of them had limited or developing IHR capacities. The top five causes of epidemics were: Cholera, Measles, Viral Haemorrhagic Diseases, Malaria and Meningitis.

Conclusions

The frequent and widespread occurrence of epidemics and disasters in Africa is a clarion call for investing in preparedness. While strengthening preparedness should be guided by global frameworks, it is the responsibility of each government to finance country specific needs. We call upon all African countries to establish governance and predictable financing mechanisms for IHR implementation and to build resilient health systems everywhere.
How to judge pelvic malposition when assessing acetabular index in children? Three simple parameters can determine acceptability
Authors: Yang Yi , Porter Daniel , Zhao Li , Zhao Xiang , Yang Xuan , Chen Suxian
Published: January 2020

Background

The acetabular index (AI) is the most commonly used parameter for diagnosing hip dysplasia. Pelvic malposition can result in misinterpretation of AI measurement especially in younger children. We aimed to investigate the correlation between pelvic orientation and acetabular index (AI) by using digital reconstructed radiographs (DRRs) and identify reliable parameters predictive of pelvic orientation on plain radiographs.

Methods

We retrospectively identified 33 children (52 hips) who received dual source CT examinations. Virtual pelvic models were reconstructed after scanning. After orientating in the standard neutral position, the models were rotated and tilted around corresponding axes. DRRs were generated at every 3° during the process. The acetabular index, the horizontal diameter (Dh) and vertical diameter (Dv) of bilateral obturator foramina, the vertical distance (h) between upper border of pubic symphysis, and Hilgenreiner’s line were measured on each DRR by two independent observers. Rotation index (Rr = right Dh/left Dh), tilt index (Rt = h/Dv), intra-observer error, and inter-observer error of AI were calculated.

Results

For tilt and rotation up to 12.0°, AI increased with anterior tilt and decreased with posterior tilt. And for rotation, it increased on the side toward which the pelvis rotated and decreased on the opposite side. AI varied dramatically if angulation exceeded 6.0°. Malposition below this limit demonstrated the intra- and inter-observer errors were ± 2.0° and ± 3.0° respectively and caused no significant effect on AI measurement.

Conclusions

For children up to age 6 years, an acceptable pelvic plain radiograph can be determined when Rt is approximately between 0.9 and 1.4 and Rr between 0.7 and 1.5. For the first time, we have identified parameters derived from a group of subjects which can predict this degree of malposition. The parameters obturator diameters (Dh), obturator height (Dv), and distance (h) between symphysis and Hilgengreiner’s line can be feasibly measured on X-ray and employed in clinical practice to assess the acceptability of the pediatric pelvic radiograph prior to measurement of the AI.
Correction of marked sagittal deformity with circumferential minimally invasive surgery using oblique lateral interbody fusion in adult spinal deformity
Authors: Park Seung Won , Ko Myeong Jin , Kim Young Baeg , Le Huec Jean Charles
Published: January 2020

Background

Spinal surgery performed entirely with minimally invasive surgery is referred to as circumferential MIS (cMIS). However, cMIS still has a limited sagittal correction capability for adult spinal deformity (ASD) with a marked sagittal deformity. We investigated the effectiveness of cMIS using oblique lateral interbody fusion (OLIF) and percutaneous posterior spine fixation in correcting marked sagittal deformity.

Methods

This study retrospectively evaluated 23 patients with ASD with marked sagittal deformity who underwent cMIS using OLIF without osteotomy and were followed-up for at least 24 months (whole group). The whole group was divided into the following two groups according to the type of interbody fusion at L5–S1: the OLIF51 group (n = 13) underwent OLIF at L1–L5 and L5–S1 and the TLIF51 group (n = 10) underwent OLIF at L1–L5 and transforaminal lumbar interbody fusion (TLIF) at L5–S1.

Results

Sagittal vertebral axis (SVA; 125.7 vs. 29.5 mm, p < 0.001), lumbar lordosis (LL; 18.2° vs. 51.7°, p < 0.001), and pelvic incidence-LL mismatch (PI-LL, 35.5° vs. 5.3°) significantly improved postoperatively in the whole group. The OLIF51 group showed significantly higher postoperative LL than the TLIF51 group (55.5° vs. 46.9°, p < 0.001). OLIF yielded a significantly greater disc angle at L5–S1 than did TLIF (18.4° vs. 6.9°, p < 0.001). Proximal junctional kyphosis occurred significantly earlier in the OLIF51 group than in the TLIF51 group (8.6 vs. 26.3 months, p < 0.001).

Conclusion

Successful sagittal correction in ASD patients with marked sagittal deformity was achieved with cMIS using OLIF. OLIF at L5–S1 showed a synergistic effect in sagittal deformity correction by cMIS.
Cross-cutting view of current challenges in paediatric solid organ and haematopoietic stem cell transplantation in Europe: the European Reference Network TransplantChild
Authors:   On behalf of ERN TransplantChild, Jara P. , Baker A. , Baumann U. , Borobia A. M. , Branchereu S. , Candusso M. , Carcas A. J. , Chardot C. , Cobas J. , D’Antiga L. , Ferreras C. , Fitzpatrick E. , Frauca E. , Hernández-Oliveros F. , Kaliciński P. , Lindemans C. , Lopes M. F. , López-Granados E. , de Magnée C. , Mota C. , Muñoz J. M. , Ojeda J. J. , Pérez-Martínez A. , Perilongo G. , Rascon J. , Sciveres M. , Stone R. , Tarutis V. , Toporski J. , Torres J. M. , Wennberg L.
Published: January 2020

The low prevalence of European paediatric transplanted patients and scarcity of resources and expertise led to the need for a multidisciplinary network able to improve the quality of life of paediatric patients and families requiring a solid organ or haematopoietic stem cell transplantation. The European Reference Network (ERN) TransplantChild is one of the 24 ERNs established in a European legal framework to improve the care of patients with rare diseases. ERN TransplantChild is the only ERN focused on both solid organ and haematopoietic stem cell paediatric transplantation, based on the understanding of paediatric transplantation as a complex and highly specialised process where specific complications appear regardless the organ involved, thus linking the skills and knowledge of different organ disciplines. Gathering European centres of expertise in paediatric transplantation will give access to a correct and timely diagnosis, share expertise and knowledge and collect a critical mass of patients and data that increases the speed and value of clinical research outcomes. Therefore, the ERN TransplantChild aims for a paediatric Pan-European, Pan-transplant approach.
Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse
Authors: Lesperance Lee Stephen , Yang Yi-Mei , Wang Lu-Yang
Published: January 2020

Developing central synapses exhibit robust plasticity and undergo experience-dependent remodeling. Evidently, synapses in sensory systems such as auditory brainstem circuits mature rapidly to achieve high-fidelity neurotransmission for sound localization. This depends on a developmental switch in AMPAR composition from slow-gating GluA1-dominant to fast-gating GluA4-dominant, but the mechanisms underlying this switch remain unknown. We hypothesize that patterned stimuli mimicking spontaneous/sound evoked activity in the early postnatal stage drives this gating switch. We examined activity-dependent changes in evoked and miniature excitatory postsynaptic currents (eEPSCs and mEPSCs) at the calyx of Held synapse by breaking through the postsynaptic membrane at different time points following 2 min of theta burst stimulation (TBS) to afferents in mouse brainstem slices. We found the decay time course of eEPSCs accelerated, but this change was not apparent until > 30 min after TBS. Histogram analyses of the decay time constants of mEPSCs for naive and tetanized synapses revealed two populations centered around τfast ≈ 0.4 and 0.8 ms, but the relative weight of the τ0.4 population over the τ0.8 population increased significantly only in tetanized synapses. Such changes are blocked by NMDAR or mGluR1/5 antagonists or inhibitors of CaMKII, PKC and protein synthesis, and more importantly precluded in GluA4−/− synapses, suggesting GluA4 is the substrate underlying the acceleration. Our results demonstrate a novel form of plasticity working through NMDAR and mGluR activation to trigger a gating switch of AMPARs with a temporally delayed onset of expression, ultimately enhancing the development of high-fidelity synaptic transmission.
FMF is not always “fever”: from clinical presentation to “treat to target”
Authors: Maggio Maria Cristina , Corsello Giovanni
Published: January 2020

Familial Mediterranean Fever, a monogenic autoinflammatory disease secondary to MEFV gene mutations in the chromosome 16p13, is characterized by recurrent self-limiting attacks of fever, arthritis, aphthous changes in lips and/or oral mucosa, erythema, serositis. It is caused by dysregulation of the inflammasome, a complex intracellular multiprotein structure, commanding the overproduction of interleukin 1. Familial Mediterranean Fever can be associated with other multifactorial autoinflammatory diseases, as vasculitis and Behçet disease.

Symptoms frequently start before 20 years of age and are characterized by a more severe phenotype in patients who begin earlier.

Attacks consist of fever, serositis, arthritis and high levels of inflammatory reactants: C-reactive protein, erythrocyte sedimentation rate, serum amyloid A associated with leucocytosis and neutrophilia. The symptom-free intervals are of different length.

The attacks of Familial Mediterranean Fever can have a trigger, as infections, stress, menses, exposure to cold, fat-rich food, drugs.

The diagnosis needs a clinical definition of the disease and a genetic confirmation. An accurate differential diagnosis is mandatory to exclude infective agents, autoimmune diseases, etc.

In many patients there is no genetic confirmation of the disease; furthermore, some subjects with the relieve of MEFV mutations, show a phenotype not in line with the diagnosis of Familial Mediterranean Fever. For these reasons, diagnostic criteria were developed, as Tel Hashomer Hospital criteria, the “Turkish FMF Paediatric criteria”, the “clinical classification criteria for autoinflammatory periodic fevers” formulated by PRINTO.

The goals of the treatment are: prevention of attacks recurrence, normalization of inflammatory markers, control of subclinical inflammation in attacks-free intervals and prevention of medium and long-term complications, as amyloidosis. Colchicine is the first step in the treatment; biological drugs are effective in non-responder patients.

The goal of this paper is to give a wide and broad review to general paediatricians on Familial Mediterranean Fever, with the relative diagnostic, clinical and therapeutic aspects.
p66ShcA functions as a contextual promoter of breast cancer metastasis
Authors: Lewis Kyle , Kiepas Alex , Hudson Jesse , Senecal Julien , Ha Jacqueline R. , Voorand Elena , Annis Matthew G. , Sabourin Valerie , Ahn Ryuhjin , La Selva Rachel , Tabariès Sébastien , Hsu Brian E. , Siegel Matthew J. , Dankner Matthew , Canedo Eduardo Cepeda , Lajoie Mathieu , Watson Ian R. , Brown Claire M. , Siegel Peter M. , Ursini-Siegel Josie
Published: January 2020

Background

The p66ShcA redox protein is the longest isoform of the Shc1 gene and is variably expressed in breast cancers. In response to a variety of stress stimuli, p66ShcA becomes phosphorylated on serine 36, which allows it to translocate from the cytoplasm to the mitochondria where it stimulates the formation of reactive oxygen species (ROS). Conflicting studies suggest both pro- and anti-tumorigenic functions for p66ShcA, which prompted us to examine the contribution of tumor cell-intrinsic functions of p66ShcA during breast cancer metastasis.

Methods

We tested whether p66ShcA impacts the lung-metastatic ability of breast cancer cells. Breast cancer cells characteristic of the ErbB2+/luminal (NIC) or basal (4T1) subtypes were engineered to overexpress p66ShcA. In addition, lung-metastatic 4T1 variants (4T1-537) were engineered to lack endogenous p66ShcA via Crispr/Cas9 genomic editing. p66ShcA null cells were then reconstituted with wild-type p66ShcA or a mutant (S36A) that cannot translocate to the mitochondria, thereby lacking the ability to stimulate mitochondrial-dependent ROS production. These cells were tested for their ability to form spontaneous metastases from the primary site or seed and colonize the lung in experimental (tail vein) metastasis assays. These cells were further characterized with respect to their migration rates, focal adhesion dynamics, and resistance to anoikis in vitro. Finally, their ability to survive in circulation and seed the lungs of mice was assessed in vivo.

Results

We show that p66ShcA increases the lung-metastatic potential of breast cancer cells by augmenting their ability to navigate each stage of the metastatic cascade. A non-phosphorylatable p66ShcA-S36A mutant, which cannot translocate to the mitochondria, still potentiated breast cancer cell migration, lung colonization, and growth of secondary lung metastases. However, breast cancer cell survival in the circulation uniquely required an intact p66ShcA S36 phosphorylation site.

Conclusion

This study provides the first evidence that both mitochondrial and non-mitochondrial p66ShcA pools collaborate in breast cancer cells to promote their maximal metastatic fitness.
Model-based exploration of the impact of glucose metabolism on the estrous cycle dynamics in dairy cows
Authors: Omari Mohamed , Lange Alexander , Plöntzke Julia , Röblitz Susanna
Published: January 2020

Background

Nutrition plays a crucial role in regulating reproductive hormones and follicular development in cattle. This is visible particularly during the time of negative energy balance at the onset of milk production after calving. Here, elongated periods of anovulation have been observed, resulting from alterations in luteinizing hormone concentrations, likely caused by lower glucose and insulin concentrations in the blood. The mechanisms that result in a reduced fertility are not completely understood, although a close relationship to the glucose-insulin metabolism is widely supported.

Results

Following this idea, we developed a mathematical model of the hormonal network combining reproductive hormones and hormones that are coupled to the glucose compartments within the body of the cow. The model is built on ordinary differential equations and relies on previously introduced models on the bovine estrous cycle and the glucose-insulin dynamics. Necessary modifications and coupling mechanisms are thoroughly discussed. Depending on the composition and the amount of feed, in particular the glucose content in the dry matter, the model quantifies reproductive hormones and follicular development over time. Simulation results for different nutritional regimes in lactating and non-lactating dairy cows are examined and compared with experimental studies. The simulations describe realistically the effects of nutritional glucose supply on the ovulatory cycle of dairy cattle.

Conclusions

The mathematical model enables the user to explore the relationship between nutrition and reproduction by running simulations and performing parameter studies. Regarding its applicability, this work is an early attempt towards developing in silico feeding strategies and may eventually help to refine and reduce animal experiments.

Reviewers

This article was reviewed by John McNamara and Tin Pang (nominated by Martin Lercher).
CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases (CARBON): study protocol for a phase IB/IIA randomised controlled trial
Authors: Coleman Rob , Brown Janet , Rathbone Emma , Flanagan Louise , Reid Amber , Kendall Jessica , Howell Sacha , Twelves Chris , Palmieri Carlo , Anand Anjana , MacPherson Iain , Brown Sarah
Published: January 2020

Background

A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement.

Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.

Methods/design

CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.

Discussion

The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.

Trial registration

ISRCTN, ISRCTN92755158, Registered on 17 February 2016.
The cost-effectiveness of specialized nursing interventions for people with Parkinson’s disease: the NICE-PD study protocol for a randomized controlled clinical trial
Authors: Radder Danique L. M. , Lennaerts Herma H. , Vermeulen Hester , van Asseldonk Thies , Delnooz Cathérine C. S. , Hagen Rob H. , Munneke Marten , Bloem Bastiaan R. , de Vries Nienke M.
Published: January 2020

Background

Current guidelines recommend that every person with Parkinson’s disease (PD) should have access to Parkinson’s disease nurse specialist (PDNS) care. However, there is little scientific evidence of the cost-effectiveness of PDNS care. This hampers wider implementation, creates unequal access to care, and possibly leads to avoidable disability and costs. Therefore, we aim to study the (cost-)effectiveness of specialized nursing care provided by a PDNS compared with usual care (without PDNS) for people with PD in all disease stages. To gain more insight into the deployed interventions and their effects, a preplanned subgroup analysis will be performed on the basis of disease duration (diagnosis < 5, 5–10, or > 10 years ago).

Methods

We will perform an 18-month, single-blind, randomized controlled clinical trial in eight community hospitals in the Netherlands. A total of 240 people with PD who have not been treated by a PDNS over the past 2 years will be included, independent of disease severity or duration. In each hospital, 30 patients will randomly be allocated in a 1:1 ratio to receive either care by a PDNS (who works according to a recent guideline on PDNS care) or usual care. We will use two co-primary outcomes: quality of life (measured with the Parkinson’s Disease Questionnaire-39) and motor symptoms (measured with the Movement Disorders Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale part III). Secondary outcomes include nonmotor symptoms, health-related quality of life, experienced quality of care, self-management, medication adherence, caregiver burden, and coping skills. Data will be collected after 12 months and 18 months by a blinded researcher. A healthcare utilization and productivity loss questionnaire will be completed every 3 months.

Discussion

The results of this trial will have an immediate impact on the current care of people with PD. We hypothesize that by offering more patients access to PDNS care, quality of life will increase. We also expect healthcare costs to remain equal because increases in direct medical costs (funding additional nurses) will be offset by a reduced number of consultations with the general practitioner and neurologist. If these outcomes are reached, wide implementation of PDNS care will be warranted.

Trial registration

ClinicalTrials.gov, NCT03830190. Registered February 5, 2019 (retrospectively registered).
Evaluating a digital tool for supporting breast cancer patients: a randomized controlled trial protocol (ADAPT)
Authors: Lidington Emma , McGrath Sophie E , Noble Jillian , Stanway Susannah , Lucas Amanda , Mohammed Kabir , van der Graaf Winette , Husson Olga
Published: January 2020

Background

There are a growing number of mHealth tools for breast cancer patients but a lack of scientific evidence for their effects. Recent studies have shown a mix of positive and negative impacts on users. Here we will assess the impact of OWise Breast Cancer, a mobile application for self-monitoring symptoms and managing care, on the process of self-management.

Methods

This randomized controlled trial with early stage breast cancer patients will assess the effect of OWise use on patient activation at 3 months from diagnosis measured by the PAM-13 questionnaire. We will also assess differences in changes in health-related quality of life, psychological distress, health status, and National Health Service (NHS) health resource utilization over the first year from diagnosis. Participants will be randomly allocated (1:1) to standard care or standard care plus OWise. Participants will complete questionnaires before starting anti-cancer treatment and at 3, 6, and 12 months from diagnosis. Clinical and patient-reported outcome data will be linked to health resource utilization data from Discover, an integrated care record of primary, secondary, and social care in North West London. We will measure contamination in the control group and adjust the sample size to mitigate the dilution of effect estimates. A per-protocol analysis will be conducted as a sensitivity analysis to assess robustness of the primary results.

Discussion

This study aims to generate evidence for the effectiveness of OWise at improving patient activation for women with early-stage breast cancer. The results will show the impact of using the tool at the patient level and the NHS health system level. The outcomes of the study will have implications for the application of OWise across the NHS for breast cancer patients and expansion into other tumor types. Assessing publicly available mHealth tools poses a challenge to trialists due to the risk of contamination. Here we apply various methods to measure, mitigate, and assess the effects of contamination.

Trial registration

The study was registered at clincaltrials.gov (NCT03866655) on 7 March 2019.
Moderators of the effectiveness of an intervention to increase colorectal cancer screening through mailed fecal immunochemical test kits: results from a pragmatic randomized trial
Authors: O’Connor Elizabeth A. , Vollmer William M. , Petrik Amanda F. , Green Beverly B. , Coronado Gloria D.
Published: January 2020

Background

Colorectal cancer (CRC) screening rates remain suboptimal, particularly in low-income and underserved populations. Mailed fecal immunochemical testing (FIT) may overcome common barriers to screening; however, the effect of mailed FIT kits may differ across important subpopulations. The goal of the current study was to examine sociodemographic and health-related factors that moderate the effect of an intervention of automated direct mail of FIT kits at health clinics serving low-income populations.

Methods

This study is a secondary analysis of the Strategies and Opportunities to Stop Colon Cancer in Priority Populations (STOP CRC) study, a cluster-randomized pragmatic trial to increase uptake of CRC screening in patients seen at federally qualified health centers. The intervention involved tools embedded in the electronic medical records to enable participating clinics to mail FIT kits and related materials to eligible participants. We examined the rate of FIT completion by potential moderating characteristics using electronic health record data supplemented by the American Community Survey and the Centers for Medicare & Medicaid Services Geographic Variation datasets, linked via geocoding to patients’ addresses. All patients aged 50–75 seen in participating health clinics who were eligible for CRC screening were included.

Results

Although not always statistically significant, we saw a consistent pattern of increased FIT return rates among intervention participants compared to control participants across all subgroups studied, with incidence rate ratios (IRRs) generally ranging from 1.25 to 1.50. FIT completion in the intervention group ranged from 15 and 20% across subpopulations, typically three to six percentage points higher than the control group participants. The only moderator with a statistically significant interaction was race: persons of Asian descent showed a twofold response to the intervention (adjusted incidence rate ratio [aIRR] = 2.06, 95% confidence interval 1.41 to 3.00).

Conclusions

Response to a mailed FIT intervention was generally consistent across a wide range of individual and neighborhood-level patient characteristics, including typically underserved patients and those in low-resource communities.

Trial registration

ClinicalTrials.gov, NCT01742065. Registered on 5 December 2012.
A pilot randomized controlled trial of 7 versus 14 days of antibiotic treatment for bloodstream infection on non-intensive care versus intensive care wards
Authors:   on behalf of the Canadian Critical Care Trials Group, Daneman Nick , Rishu Asgar H. , Pinto Ruxandra , Arabi Yaseen , Belley-Cote Emilie P. , Cirone Robert , Downing Mark , Cook Deborah J. , Hall Richard , McGuinness Shay , McIntyre Lauralyn , Muscedere John , Parke Rachael , Reynolds Steven , Rogers Benjamin A. , Shehabi Yahya , Shin Phillip , Whitlock Richard , Fowler Robert A.
Published: January 2020

Background

The optimal treatment duration for patients with bloodstream infection is understudied. The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) pilot randomized clinical trial (RCT) determined that it was feasible to enroll and randomize intensive care unit (ICU) patients with bloodstream infection to 7 versus 14 days of treatment, and served as the vanguard for the ongoing BALANCE main RCT. We performed this BALANCE-Ward pilot RCT to examine the feasibility and impact of potentially extending the BALANCE main RCT to include patients hospitalized on non-ICU wards.

Methods

We conducted an open pilot RCT among a subset of six sites participating in the ongoing BALANCE RCT, randomizing patients with positive non-Staphylococcus aureus blood cultures on non-ICU wards to 7 versus 14 days of antibiotic treatment. The co-primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. We compared feasibility outcomes, patient/pathogen characteristics, and overall outcomes among those enrolled in this BALANCE-Ward and prior BALANCE-ICU pilot RCTs. We estimated the sample size and non-inferiority margin impacts of expanding the BALANCE main RCT to include non-ICU patients.

Results

A total of 134 patients were recruited over 47 site-months (mean 2.9 patients/site-month, median 1.0, range 0.1–4.4 patients/site-month). The overall recruitment rate exceeded the BALANCE-ICU pilot RCT (mean 1.10 patients/site-month, p < 0.0001). Overall protocol adherence also exceeded the adherence in the BALANCE-ICU pilot RCT (125/134, 93% vs 89/115, 77%, p = 0.0003). BALANCE-Ward patients were older, with lower Sequential Organ Failure Assessment scores, and higher proportions of infections caused by Escherichia coli and genito-urinary sources of bloodstream infection. The BALANCE-Ward pilot RCT patients had an overall 90-day mortality rate of 17/133 (12.8%), which was comparable to the 90-day mortality rate in the ICU pilot RCT (17/115, 14.8%) (p = 0.65). Simulation models indicated there would be minimal sample size and non-inferiority margin implications of expanding enrolment to increasing proportions of non-ICU versus ICU patients.

Conclusion

It is feasible to enroll non-ICU patients in a trial of 7 versus 14 days of antibiotics for bloodstream infection, and expanding the BALANCE RCT hospital-wide has the potential to improve the timeliness and generalizability of trial results.

Trial registration

Clinicaltrials.gov, NCT02917551. Registered on September 28, 2016.
The mosquito electrocuting trap as an exposure-free method for measuring human-biting rates by Aedes mosquito vectors
Authors: Ortega-López Leonardo D. , Pondeville Emilie , Kohl Alain , León Renato , Betancourth Mauro Pazmiño , Almire Floriane , Torres-Valencia Sergio , Saldarriaga Segundo , Mirzai Nosrat , Ferguson Heather M.
Published: January 2020

Background

Entomological monitoring ofAedesvectors has largely relied on surveillance of larvae, pupae and non-host-seeking adults, which have been poorly correlated with human disease incidence. Exposure to mosquito-borne diseases can be more directly estimated using human landing catches (HLC), although this method is not recommended forAedes-borne arboviruses. We evaluated a new method previously tested with malaria vectors, the mosquito electrocuting trap (MET) as an exposure-free alternative for measuring landing rates ofAedesmosquitoes on people. Aims were to (i) compare the MET to the BG-sentinel (BGS) trap gold standard approach for sampling host-seekingAedesvectors; and (ii) characterize the diel activity ofAedesvectors and their association with microclimatic conditions.

Methods

The study was conducted over 12 days in Quinindé (Ecuador) in May 2017. Mosquito sampling stations were set up in the peridomestic area of four houses. On each day of sampling, each house was allocated either a MET or a BGS trap, which were rotated amongst the four houses daily in a Latin square design. Mosquito abundance and microclimatic conditions were recorded hourly at each sampling station between 7:00–19:00 h to assess variation between vector abundance, trapping methods, and environmental conditions. AllAedes aegyptifemales were tested for the presence of Zika (ZIKV), dengue (DENV) and chikungunya (CHIKV) viruses.

Results

A higher number ofAe. aegyptifemales were found in MET than in BGS collections, although no statistically significant differences in meanAe. aegyptiabundance between trapping methods were found. Both trapping methods indicated femaleAe. aegyptihad bimodal patterns of host-seeking, being highest during early morning and late afternoon hours. MeanAe. aegyptidaily abundance was negatively associated with daily temperature. No infection by ZIKV, DENV or CHIKV was detected in anyAedesmosquitoes caught by either trapping method.

Conclusion

We conclude the MET performs at least as well as the BGS standard and offers the additional advantage of direct measurement ofper capitahuman-biting rates. If detection of arboviruses can be confirmed in MET-collectedAedesin future studies, this surveillance method could provide a valuable tool for surveillance and prediction on human arboviral exposure risk.
Validation of prediction models of severe disease course and non-achievement of remission in juvenile idiopathic arthritis part 2: results of the Nordic model in the Canadian cohort
Authors:   for the ReACCh-Out and NoSPeR Investigators, Henrey Andrew , Rypdal Veronika , Rypdal Martin , Loughin Thomas , Nordal Ellen , Guzman Jaime
Published: January 2020

Background

Validated clinical prediction models to identify children with poor prognosis at the time of juvenile idiopathic arthritis (JIA) diagnosis would be very helpful for tailoring treatments, and avoiding under- or over-treatment. Our objective was to externally validate Nordic clinical prediction models in Canadian patients with JIA.

Methods

We used data from 513 subjects at the 3-year follow-up from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcomes were non-achievement of remission, severe disease course, and functional disability. The Nordic models were evaluated exactly as published and after fine-tuning the logistic regression coefficients using multiple data splits of the Canadian cohort. Missing data was handled with multiple imputation, and prediction ability was assessed with C-indices. C-index values > 0.7 were deemed to reflect helpful prediction.

Results

Overall, 81% of evaluable patients did not achieve remission off medications, 15% experienced a severe disease course, and 38% reported disability (CHAQ score > 0). The Nordic model for predicting non-achievement of remission had a C-index of 0.68 (95% CI 0.62–0.74), and 0.74 (0.67–0.80) after fine-tuning. For prediction of severe disease course, it had a C-index of 0.69 (0.61–0.78), and 0.79 (0.68–0.91) after fine-tuning. The fine-tuned Nordic model identified 85% of the cohort as low risk for a severe disease course (< 20% chance) and 7% as high risk (> 60% chance). The Nordic model to predict functional disability had a C-index of 0.57 (0.50–0.63), and 0.51 (0.39–0.63) after fine-tuning.

Conclusions

Fine-tuned Nordic models, combining active joint count, physician global assessment of disease activity, morning stiffness, and ankle involvement, predicted well non-achievement of remission and severe disease course in Canadian patients with JIA. The Nordic model for predicting disability could not predict functional disability in Canadian patients.
Psychometric properties of the Adelaide Diagnostic Learning Inventory-Brief (ADLIB)
Authors: Minas Harry
Published: January 2020

Objective

There has been increased attention in recent years to mental health, quality of life, stress and academic performance among university students, and the possible influence of learning styles. Brief reliable questionnaires are useful in large-scale multivariate research designs, such as the largely survey-based research on well-being and academic performance of university students. The objective of this study was to examine the psychometric properties of a briefer version of the 39-item Adelaide Diagnostic Learning Inventory.

Results

In two survey samples—medical and physiotherapy students—a 21-item version Adelaide Diagnostic Learning Inventory-Brief (ADLIB) was shown to have the same component structure as the parent instrument, and the component structure of the brief instrument was found to generalise across students of medicine and physiotherapy. Subscale reliability estimations were in the order of magnitude of the parent instrument. Subscale inter-correlations, inter-component congruence coefficients, and correlations between ADLIB subscale scores and several external measures provide support support for the construct and criterion validity of the instrument.
Tobacco and electronic cigarette cues for smoking and vaping: an online experimental study
Authors: Blackwell Anna K. M. , De-loyde Katie , Brocklebank Laura A. , Maynard Olivia M. , Marteau Theresa M. , Hollands Gareth J. , Fletcher Paul C. , Attwood Angela S. , Morris Richard W. , Munafò Marcus R.
Published: January 2020

Objective

This study examined whether exposure to smoking and vaping cues the urge to smoke or vape. It extends previous studies on first-generation cigalikes (visually similar to cigarettes) and second-generation devices (visually similar to pens) by including third-generation tank system devices (larger bulky units). In an online experiment, participants were randomly assigned to view one of four videos, which included smoking, vaping (cigalike or tank system), or neutral cues. The primary outcome was urge to smoke. Secondary outcomes were urge to vape, desire to smoke and vape, and intention to quit or remain abstinent from smoking.

Results

UK adults varying in smoking (current or former) and vaping (user or non-user) status (n = 1120) completed the study: 184 (16%) failed study attention checks meaning 936 were included in the final analysis. Urges to smoke were similar across cue groups. Urges to vape were higher following exposure to vaping compared to neutral cues. There was no clear evidence of an interaction between cue group and smoking or vaping status. The lack of cueing effects on smoking urges is inconsistent with previous research, raising questions about the ability to assess craving in online settings.
Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up
Authors: Bernaerts Sylvie , Boets Bart , Bosmans Guy , Steyaert Jean , Alaerts Kaat
Published: January 2020

Background

Intranasal administration of the “prosocial” neuropeptide oxytocin is increasingly explored as a potential treatment for targeting the core characteristics of autism spectrum disorder (ASD). However, long-term follow-up studies, evaluating the possibility of long-lasting retention effects, are currently lacking.

Methods

Using a double-blind, randomized, placebo-controlled, parallel design, this pilot clinical trial explored the possibility of long-lasting behavioral effects of 4 weeks of intranasal oxytocin treatment (24 International Units once daily in the morning) in 40 adult men with ASD. To do so, self-report and informant-based questionnaires assessing core autism symptoms and characterizations of attachment were administered at baseline, immediately after 4 weeks of treatment (approximately 24 h after the last nasal spray administration), and at two follow-up sessions, 4 weeks and 1 year post-treatment.

Results

No treatment-specific effects were identified in the primary outcome assessing social symptoms (Social Responsiveness Scale, self- and informant-rated). In particular, with respect to self-reported social responsiveness, improvements were evident both in the oxytocin and in the placebo group, yielding no significant between-group difference (p = .37). Also informant-rated improvements in social responsiveness were not significantly larger in the oxytocin, compared to the placebo group (between-group difference: p = .19). Among the secondary outcome measures, treatment-specific improvements were identified in the Repetitive Behavior Scale and State Adult Attachment Measure, indicating reductions in self-reported repetitive behaviors (p = .04) and reduced feelings of avoidance toward others (p = .03) in the oxytocin group compared to the placebo group, up to 1 month and even 1 year post-treatment. Treatment-specific effects were also revealed in screenings of mood states (Profile of Mood States), indicating higher reports of “vigor” (feeling energetic, active, lively) in the oxytocin, compared to the placebo group (p = .03).

Conclusions

While no treatment-specific improvements were evident in terms of core social symptoms, the current observations of long-term beneficial effects on repetitive behaviors and feelings of avoidance are promising and suggestive of a therapeutic potential of oxytocin treatment for ASD. However, given the exploratory nature of this pilot study, future studies are warranted to evaluate the long-term effects of OT administration further.

Trial registration

The trial was registered with the European Clinical Trial Registry (Eudract 2014-000586-45) on January 22, 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000586-45/BE).
A rare association between true thymic hyperplasia and thyroid follicular tumor: a case report
Authors: Kiwaki Takumi , Tanaka Hiroyuki , Akiyama Yutaka , Akaki Mayumi , Tomita Masaki , Kataoka Hiroaki
Published: January 2020

Background

True thymic hyperplasia is a rare condition characterized by enlargement of the thymus while its normal structure is retained. True thymic hyperplasia is known to accompany Graves’ disease, but no association between true thymic hyperplasia and thyroid follicular tumor has been reported so far. We report a case of true thymic hyperplasia in a patient with a thyroid follicular tumor.

Case presentation

A 52-year-old Japanese man was referred to our hospital for evaluation of a thyroid mass and a mediastinal mass. His serum thyroglobulin level was high, and hemithyroidectomy was performed to remove the thyroid mass. The resected mass was diagnosed as a follicular tumor of uncertain malignant potential. After resection of the thyroid lesion, the patient’s serum thyroglobulin levels were markedly decreased. Seven months later, the patient underwent resection of the mediastinal mass. On pathological examination, the mass was found to consist of lobules, which formed a corticomedullary structure with Hassall’s bodies, indicating a normal thymic mass with hyperplastic thymic tissue, less organized cellular cords, and intermingled adipose tissue. Immunostaining for cytokeratin 19 and cytokeratin 7 indicated that the lesion was consistent with thymic tissue. The lesion was diagnosed as true thymic hyperplasia, and the histological findings suggested that secondary atrophy had occurred. No evidence of recurrence was observed at 24 months after surgery.

Conclusions

We present a case of a combination of true thymic hyperplasia and thyroidal follicular tumors that, to our knowledge, has not been reported previously. High serum thyroglobulin levels might play a role in hyperplasia of the thymus. Although true thymic hyperplasia is a rare disorder, it should be included in the differential diagnosis of a mediastinal mass in patients with thyroid disease.
Biomarkers and clinical scores to aid the identification of disease severity and intensive care requirement following activation of an in-hospital sepsis code
Authors: Baldirà Jaume , Ruiz-Rodríguez Juan Carlos , Wilson Darius Cameron , Ruiz-Sanmartin Adolf , Cortes Alejandro , Chiscano Luis , Ferrer-Costa Roser , Comas Inma , Larrosa Nieves , Fàbrega Anna , González-López Juan José , Ferrer Ricard
Published: January 2020

Background

Few validated biomarker or clinical score combinations exist which can discriminate between cases of infection and other non-infectious conditions following activation of an in-hospital sepsis code, as well as provide an accurate severity assessment of the corresponding host response. This study aimed to identify suitable blood biomarker (MR-proADM, PCT, CRP and lactate) or clinical score (SOFA and APACHE II) combinations to address this unmet clinical need.

Methods

A prospective, observational study of patients activating the Vall d’Hebron University Hospital sepsis code (ISC) within the emergency department (ED), hospital wards and intensive care unit (ICU). Area under the receiver operating characteristic (AUROC) curves, logistic and Cox regression analysis were used to assess performance.

Results

148 patients fulfilled the Vall d’Hebron ISC criteria, of which 130 (87.8%) were retrospectively found to have a confirmed diagnosis of infection. Both PCT and MR-proADM had a moderate-to-high performance in discriminating between infected and non-infected patients following ISC activation, although the optimal PCT cut-off varied significantly across departments. Similarly, MR-proADM and SOFA performed well in predicting 28- and 90-day mortality within the total infected patient population, as well as within patients presenting with a community-acquired infection or following a medical emergency or prior surgical procedure. Importantly, MR-proADM also showed a high association with the requirement for ICU admission after ED presentation [OR (95% CI) 8.18 (1.75–28.33)] or during treatment on the ward [OR (95% CI) 3.64 (1.43–9.29)], although the predictive performance of all biomarkers and clinical scores diminished between both settings.

Conclusions

Results suggest that the individual use of PCT and MR-proADM might help to accurately identify patients with infection and assess the overall severity of the host response, respectively. In addition, the use of MR-proADM could accurately identify patients requiring admission onto the ICU, irrespective of whether patients presented to the ED or were undergoing treatment on the ward. Initial measurement of both biomarkers might therefore facilitate early treatment strategies following activation of an in-hospital sepsis code.
The controllability of fractional differential system with state and control delay
Authors: Nawaz Musarrat , Wei Jiang , Jiale Sheng
Published: January 2020

In this research work, we investigate the controllability of linear fractional differential control systems with state and control delay. By using an explicit solution formula, a rank criterion for controllability is established. For the controllability criteria, we establish necessary and sufficient conditions of a fractional differential systems with state and control delay. In the end, a numerical example is constructed to support the results.
A modified analytical approach with existence and uniqueness for fractional Cauchy reaction–diffusion equations
Authors: Kumar Sunil , Kumar Amit , Abbas Syed , Al Qurashi Maysaa , Baleanu Dumitru
Published: January 2020

This article mainly explores and applies a modified form of the analytical method, namely the homotopy analysis transform method (HATM) for solving time-fractional Cauchy reaction–diffusion equations (TFCRDEs). Then mainly we address the error norms $L_{2}$L2 and $L_{\infty }$L∞ for a convergence study of the proposed method. We also find existence, uniqueness and convergence in the analysis for TFCRDEs. The projected method is illustrated by solving some numerical examples. The obtained numerical solutions by the HATM method show that it is simple to employ. An excellent conformity obtained between the solution got by the HATM method and the various well-known results available in the current literature. Also the existence and uniqueness of the solution have been demonstrated.