bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare utilisation in general practice and hospitals in the year preceding a diagnosis of cancer recurrence or second primary cancer: a population-based register study
Authors: Rasmussen Linda Aagaard , Jensen Henry , Virgilsen Line Flytkjær , Falborg Alina Zalounina , Møller Henrik , Vedsted Peter
Published: December 2019

Background

The organisation of cancer follow-up is under scrutiny in many countries, and general practice is suggested to become more involved. A central focus is timely detection of recurring previous cancer and new second primary cancer. More knowledge on the patient pathway before cancer recurrence and second primary cancer is warranted to ensure the best possible organisation of follow-up. We aimed to describe the healthcare utilisation in the year preceding a diagnosis of cancer recurrence or second primary cancer.

Methods

This nationwide register study comprises patients diagnosed with bladder, breast, colorectal, endometrial, lung, malignant melanoma and ovarian cancer in Denmark in 2008–2016. The frequency of healthcare contacts during the 12 months preceding a cancer recurrence or second primary cancer was estimated and compared to the frequency of cancer survivors in cancer remission. The main analyses were stratified on sex and healthcare setting. Furthermore, two sub-analyses were stratified on 1) sex, healthcare setting and age group and on 2) sex, healthcare setting and comorbidity status.

Results

The study population consisted of 7832 patients with recurrence and 2703 patients with second primary cancer. On average, the patients were in contact with general practice one time per month in the 12th month preceding a new cancer diagnosis (recurrence or second primary cancer). Increasing contact rates were seen from 7 months before diagnosis in general practice and from 12 months before diagnosis in hospitals. This pattern was more pronounced in patients with cancer recurrence, younger patients and patients with no comorbidity. For instance, the contact rate ratios for hospital contacts in non-comorbid women with recurrence demonstrated 30% more contacts in the 12th month before recurrence and 127% more contacts in the 2nd month before recurrence.

Conclusions

The results show that cancer survivors are already seen in general practice on a regular basis. The increasing contact rates before a diagnosis of cancer recurrence or second primary cancer indicate that a window of opportunity exists for more timely diagnosis; this is seen in both general practice and in hospitals. Thus, cancer survivors may benefit from improvements in the organisation of cancer follow-up.
Improvement of shared decision making in integrated stroke care: a before and after evaluation using a questionnaire survey
Authors: Voogdt-Pruis H. R. , Ras T. , van der Dussen L. , Benjaminsen S. , Goossens P. H. , Raats I. , Boss G. , van Hoef E. F. M. , Lindhout M. , Tjon-A-Tsien M. R. S. , Vrijhoef H. J. M.
Published: December 2019

Background

Shared decision making (SDM) is at the core of policy measures for making healthcare person-centred. However, the context-sensitive nature of the challenges in integrated stroke care calls for research to facilitate its implementation. This before and after evaluation study identifies factors for implementation and concludes with key recommendations for adoption.

Methods

Data were collected at the start and end of an implementation programme in five stroke services (December 2017 to July 2018). The SDM implementation programme consisted of training for healthcare professionals (HCPs), tailored support, development of decision aids and a social map of local stroke care. Participating HCPs were included in the evaluation study: A questionnaire was sent to 25 HCPs at baseline, followed by 11 in-depth interviews. Data analysis was based on theoretical models for implementation and 51 statements were formulated as a result. Finally, all HCPs were asked to validate and to quantify these statements and to formulate recommendations for further adoption.

Results

The majority of respondents said that training of all HCPs is essential. Feedback on consultation and peer observation are considered to help improve performance. In addition, HCPs stated that SDM should also be embedded in multidisciplinary meetings, whereas implementation in the organisation could be facilitated by appointed ambassadors. Time was not seen as an inhibiting factor. According to HCPs, negotiating patients’ treatment decisions improves adherence to therapy. Despite possible cognitive or communications issues, all are convinced patients with stroke can be involved in a SDM-process. Relatives play an important role too in the further adoption of SDM. HCPs provided eight recommendations for adoption of SDM in integrated stroke care.

Conclusions

HCPs in our study indicated it is feasible to implement SDM in integrated stroke care and several well-known implementation activities could improve SDM in stroke care. Special attention should be given to the following activities: (1) the appointment of knowledge brokers, (2) agreements between HCPs on roles and responsibilities for specific decision points in the integrated stroke care chain and (3) the timely investigation of patient’s preferences in the care process – preferably before starting treatment through discussions in a multidisciplinary meeting.
Preliminary validation of the PRImary care facility Management Evaluation tool (PRIME-Tool), a national facility management survey implemented in Ghana
Authors: Uy Jhanna , Macarayan Erlyn K. , Ratcliffe Hannah L. , Miller Kate , Otupiri Easmon , Awoonor-Williams John Koku , Hirschhorn Lisa R. , Lipsitz Stuart R. , Schwarz Dan , Bitton Asaf
Published: December 2019

Background

The management quality of healthcare facilities has consistently been linked to facility performance, but available tools to measure management are costly to implement, often hospital-specific, not designed for low- and middle-income countries (LMICs), nor widely deployed. We addressed this gap by developing the PRImary care facility Management Evaluation Tool (PRIME-Tool), a primary health care facility management survey for integration into routine national surveys in LMICs. We present an analysis of the tool’s psychometric properties and suggest directions for future improvements.

Methods

The PRIME-Tool assesses performance in five core management domains: Target setting, Operations, Human resources, Monitoring, and Community engagement. We evaluated two versions of the PRIME-Tool. We surveyed 142 primary health care (PHC) facilities in Ghana in 2016 using the first version (27 items) and 148 facilities in 2017 using the second version (34 items). We calculated floor and ceiling effects for each item and conducted exploratory factor analyses to examine the factor structure for each year and version of the tool. We developed a revised management framework and PRIME-tool as informed by these exploratory results, further review of management theory literature, and co-author consensus.

Results

The majority (17 items in 2016, 23 items in 2017) of PRIME-Tool items exhibited ceiling effects, but only three (2 items in 2016, 3 items in 2017) showed floor effects. Solutions suggested by factor analyses did not fully fit our initial hypothesized management domains. We found five groupings of items that consistently loaded together across each analysis and named these revised domains as Supportive supervision and target setting, Active monitoring and review, Community engagement, Client feedback for improvement, and Operations and financing.

Conclusion

The revised version of the PRIME-Tool captures a range of important and actionable information on the management of PHC facilities in LMIC contexts. We recommend its use by other investigators and practitioners to further validate its utility in PHC settings. We will continue to refine the PRIME-Tool to arrive at a parsimonious tool for tracking PHC facility management quality. Better understanding the functional components of PHC facility management can help policymakers and frontline managers drive evidence-based improvements in performance.
The X chromosome of the German cockroach, Blattella germanica, is homologous to a fly X chromosome despite 400 million years divergence
Authors: Meisel Richard P. , Delclos Pablo J. , Wexler Judith R.
Published: December 2019

Background

Sex chromosome evolution is a dynamic process that can proceed at varying rates across lineages. For example, different chromosomes can be sex-linked between closely related species, whereas other sex chromosomes have been conserved for > 100 million years. Cases of long-term sex chromosome conservation could be informative of factors that constrain sex chromosome evolution. Cytological similarities between the X chromosomes of the German cockroach (Blattella germanica) and most flies suggest that they may be homologous—possibly representing an extreme case of long-term conservation.

Results

To test the hypothesis that the cockroach and fly X chromosomes are homologous, we analyzed whole-genome sequence data from cockroaches. We found evidence in both sequencing coverage and heterozygosity that a significant excess of the same genes are on both the cockroach and fly X chromosomes. We also present evidence that the candidate X-linked cockroach genes may be dosage compensated in hemizygous males. Consistent with this hypothesis, three regulators of transcription and chromatin on the fly X chromosome are conserved in the cockroach genome.

Conclusions

Our results support our hypothesis that the German cockroach shares the same X chromosome as most flies. This may represent the convergent evolution of the X chromosome in the lineages leading to cockroaches and flies. Alternatively, the common ancestor of most insects may have had an X chromosome that resembled the extant cockroach and fly X. Cockroaches and flies diverged ∼ 400 million years ago, which would be the longest documented conservation of a sex chromosome. Cockroaches and flies have different mechanisms of sex determination, raising the possibility that the X chromosome was conserved despite the evolution of the sex determination pathway.
The British E. coli O157 in cattle study (BECS): factors associated with the occurrence of E. coli O157 from contemporaneous cross-sectional surveys
Authors: Henry Madeleine K. , McCann Catherine M. , Humphry Roger W. , Morgan Mair , Willett Alice , Evans Judith , Gunn George J. , Tongue Sue C.
Published: December 2019

Background

Escherichia coli O157 is a bacterial pathogen associated with severe disease in humans for which cattle are an important reservoir of infection. The identification of possible risk factors for infection in cattle could facilitate the development of control strategies and interventions to mitigate the risk to human health. The purpose of this study was to utilize data collected in 2014–2015 during the two contemporaneous cross-sectional surveys of the British E. coli O157 in Cattle Study (BECS) to investigate potential risk factors for E. coli O157 status in cattle destined for the food chain.

Results

In the England & Wales survey only one variable, herd size, was associated with the outcome farm-level E. coli O157 positive status. The odds increased for each additional animal in the herd. In the Scotland survey, as well as a measure of herd size (the number of cattle aged 12–30 months), having brought breeding females on to the farm in the last year also increased the odds, whereas farms sampled in spring were less likely to be positive compared to those sampled in autumn.

On the positive farms, in both surveys, an increase in the proportion of pats positive for E. coli O157 was associated with animals being housed at the time of sampling. However, the effect of housing on pat-level prevalence within positive groups was lower on farms from England & Wales than from Scotland (OR 0.45 (95% C.I. 0.24–0.86)).

Conclusion

For the first time, factors associated with farm-level E. coli O157 status have been investigated in two contemporaneous surveys with comparable study design. Although factors associated with farm-level E. coli O157 status differed between the two surveys, one consistent factor was an association with a measure of herd size. Factors associated with the proportion of E. coli O157 positive pats within a positive farm were similar in both surveys but differed from those associated with farm-level status. These findings raise the hypothesis that measures to protect public health by reducing the risk from cattle may need to be tailored, rather than by assuming that a GB-wide protocol is the best approach.
Meibomian gland dysfunction (MGD), as diagnosed by non-contact infrared Meibography, in dogs with ocular surface disorders (OSD): a retrospective study
Authors: Viñas Marta , Maggio Federica , D’Anna Nunzio , Rabozzi Roberto , Peruccio Claudio
Published: December 2019

Background

Meibomian gland dysfunction (MGD) is one of the possible conditions underlying ocular surface disorders (OSD). Prevalence of MGD in dogs affected by OSD has not yet been reported. We aimed to evaluate the prevalence of MGD among OSD canine patients, which had been assessed by non-contact infrared meibography and interferometry, and to identify MGD associated factors that might guide its diagnosis. Medical records of canine patients examined for OSD between 2016 and 2019 were reviewed. The frequency of MGD was evaluated within different categories (skull conformation, gender, eye and STT-1). The putative MGD risk factors and frequency of MGD within grades of interferometry were evaluated in a regression analysis model and reported as odd ratios (ORs).

Results

One hundred fifty eyes from 81 dogs with OSD were included with median age 75 months (range 3–192) and female representation with 52%. MGD was present in 70% of the examined eyes. MGD risk was higher in males ORadj = 3.015 (95% CI: 1.395–6.514) (P = 0.005) and older patients ORadj = 1.207 (95% CI: 1.081–1.348) (P = 0.001). No significant differences were found between left and right eyes (P = 0.66) or between the two types of skull conformation (P = 0.477) and MGD presence. MGD was associated to the lowest lipid layer (LL) thickness, as assessed by interferometry (grade 0) OR = 16.00 (95% CI: 2.104–121.68) (P < 0.001). STT values were not significantly associated with the presence of MGD (P > 0.05).

Conclusions

MGD is a common underlying pathology in OSD. Being male and higher age are risk factors for MGD. An interferometry grade 0 may guide OSD diagnosis towards MGD.
Development and clinical applications of cancer immunotherapy against PD-1 signaling pathway
Authors: Wakabayashi Grace , Lee Yu-Ching , Luh Frank , Kuo Chun-Nan , Chang Wei-Chiao , Yen Yun
Published: December 2019

Dramatic advances in immune therapy have emerged as a promising strategy in cancer therapeutics. In addition to chemotherapy and radiotherapy, inhibitors targeting immune-checkpoint molecules such as cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death receptor-1 (PD-1) and its ligand (PD-L1) demonstrate impressive clinical benefits in clinical trials. In this review, we present background information about therapies involving PD-1/PD-L1 blockade and provide an overview of current clinical trials. Furthermore, we present recent advances involving predictive biomarkers associated with positive therapeutic outcomes in cancer immunotherapy.
Effects of indoor residual spraying and outdoor larval control on Anopheles coluzzii from São Tomé and Príncipe, two islands with pre-eliminated malaria
Authors: Chen Ying-An , Lien Jih-Ching , Tseng Lien-Fen , Cheng Chien-Fu , Lin Wan-Yu , Wang Hurng-Yi , Tsai Kun-Hsien
Published: December 2019

Background

Vector control is a key component of malaria prevention. Two major vector control strategies have been implemented in São Tomé and Príncipe (STP), indoor residual spraying (IRS) and outdoor larval control usingBacillus thuringiensis israelensis(Bti). This study evaluated post-intervention effects of control strategies on vector population density, composition, and knockdown resistance mutation, and their implications for malaria epidemiology in STP.

Methods

Mosquitoes were collected by indoor and outdoor human landing catches and mosquito light traps in seven districts. Mosquito density was calculated by numbers of captured adult mosquitoes/house/working hour. Mitochondrial cytochromecoxidase subunit I (COI) was PCR amplified and sequenced to understand the spatial–temporal population composition of malaria vector in STP. Knockdown resistance L1014F mutation was detected using allele-specific PCR. To estimate the malaria transmission risks in STP, a negative binomial regression model was constructed. The response variable was monthly incidence, and the explanatory variables were area, rainfall, entomological inoculation rate (EIR), andkdrmutation frequency.

Results

Malaria vector in STP is exophilicAnopheles coluzziiwith significant population differentiation between Príncipe and São Tomé (mean FST = 0.16, p < 0.001). Both vector genetic diversity and knockdown resistance mutation were relatively low in Príncipe (mean ofkdrfrequency = 15.82%) compared to São Tomé (mean ofkdrfrequency = 44.77%). Annual malaria incidence rate in STP had been rapidly controlled from 37 to 2.1% by three rounds of country-wide IRS from 2004 to 2007. Long-term application ofBtisince 2007 kept the mosquito density under 10 mosquitoes/house/hr/month, and malaria incidence rate under 5% after 2008, except for a rising that occurred in 2012 (incidence rate = 6.9%). Risk factors of area (São Tomé compared to Príncipe), rainfall, outdoor EIR, andkdrmutation frequency could significantly increase malaria incidence by 9.33–11.50, 1.25, 1.07, and 1.06 fold, respectively.

Conclusions

Indoor residual spraying could rapidly decreaseAnophelesdensity and malaria incidence in STP. Outdoor larval control usingBtiis a sustainable approach for controlling local vector with exophilic feature and insecticide resistance problem. Vector control interventions should be intensified especially at the north-eastern part of São Tomé to minimize impacts of outbreaks.
Changing plasma cytokine, chemokine and growth factor profiles upon differing malaria transmission intensities
Authors: Aguilar Ruth , Campo Joseph J. , Chicuecue Silvia , Cisteró Pau , Català Alba , Luis Leopoldina , Ubillos Itziar , Galatas Beatriz , Aide Pedro , Guinovart Caterina , Moncunill Gemma , Dobaño Carlota
Published: December 2019

Background

Malaria epidemiological and immunological data suggest that parasite tolerance wanes in the absence of continuous exposure to the parasite, potentially enhancing pathogenesis. The expansion of control interventions and elimination campaigns raises the necessity to better understand the host factors leading to susceptibility or tolerance that are affected by rapid changes in malaria transmission intensity (MTI). Mediators of cellular immune responses are responsible for the symptoms and pathological alterations during disease and are expected to change rapidly upon malaria exposure or cessation.

Methods

The plasma concentrations of 30 cytokine, chemokine and growth factors in individuals of all ages from a malaria endemic area of southern Mozambique were compared between 2 years of different MTI: 2010 (lower, n = 234) and 2013 (higher, n = 143). The effect of the year on the correlations between cytokines, chemokines and growth factors and IgGs toPlasmodium falciparum(markers of exposure) was explored. The effects of age, sex, neighbourhood and parasitaemia on analyte levels and their interactions with year were also assessed.

Results

An inverse correlation of several cellular immune mediators with malarial antibodies in 2013, and a lack of correlation or even a positive correlation in 2010 were observed. Most cytokines, chemokines and growth factors, regardless of their immune function, had higher concentrations in 2010 compared with 2013 inP. falciparum-infected and uninfected subjects. Age and neighbourhood showed an effect on analyte concentrations.

Conclusions

The results show a different regulation of the cellular immune response in 2010 vs 2013 which could be related to a loss of immune-tolerance after a decline in MTI in 2010 and previous years, and a rapid re-establishment of tolerance as a consequence of more continuous exposure as MTI began increasing in 2012. Cellular immune mediators warrant further investigation as possible surrogates of MTI-associated host susceptibility or tolerance.
Cultural adaptation and validation of the Norwegian version of the swallowing quality of life questionnaire (SWAL-QOL)
Authors: Rivelsrud Maribeth Caya , Kirmess Melanie , Hartelius Lena
Published: December 2019

Introduction

Oropharyngeal dysphagia (OD) is a disorder that can have devastating and long lasting effects on a person’s medical, mental and psychosocial well-being, thus negatively impacting quality of life. There is currently no validated dysphagia-specific quality of life instrument in Norway. This project aims to evaluate the psychometric properties of the culturally adapted Norwegian version of SWAL-QOL (Nor-SWAL-QOL).

Methods

The original SWAL-QOL was translated into Norwegian according the international translation guidelines. A group of 102 persons with OD and a group of 123 healthy controls were recruited to assess the validity and reliability of the Nor-SWAL-QOL. Correlation analysis of the Nor-SWAL-QOL and the Short Form 36 (SF-36) and correlation analysis of OD group and control group Nor-SWAL-QOL subscale scores were computed to determine convergent, discriminant, and known-groups validity which help comprise construct validity. Internal consistency, test-retest reliability and intraclass correlation coefficient (ICC) were computed for reliability.

Results

Convergent and discriminant validity was demonstrated between Nor-SWAL-QOL subscales and SF-36 domains, and distinguished between persons with and those without oropharyngeal dysphagia on all subscales and on the symptom frequency battery (p < 0.001). Additionally, the Nor-SWAL-QOL differentiated between symptom severity levels within the OD group; those requiring food and liquid modifications and those who are tube fed and not tube fed. Nor-SWAL-QOL showed good reliability with adequate internal consistency (Cronbach’s α ≥0.70), test-retest reliability (Spearman’s rho values 0.68–0.90) and ICC values (0.67–0.89) for all subscales and for the symptom frequency battery.

Conclusion

Access to valid and reliable dysphagia-specific QoL outcome measures for health care practitioners, dysphagia clinicians and researchers is necessary for comprehensive assessment and treatment outcome measures. The Nor-SWAL-QOL exhibits sufficient psychometric properties for implementation in the Norwegian population.
Stretch reflex excitability in contralateral limbs of stroke survivors is higher than in matched controls
Authors: Afzal Taimoor , Chardon Matthieu K. , Rymer William Z. , Suresh Nina L.
Published: December 2019

Background

Spasticity, characterized by hyperreflexia, is a motor impairment that can arise following a hemispheric stroke. While the neural mechanisms underlying spasticity in chronic stroke survivors are unknown, one probable cause of hyperreflexia is increased motoneuron (MN) excitability. Potential sources of increased spinal MN excitability after a stroke include increased vestibulospinal (VS) and/or reticulospinal (RS) drive. Spasticity, as clinically assessed in stroke survivors, is highly lateralized, thus RS contributions to stroke-induced spasticity are more difficult to reconcile, as RS nuclei routinely project bilaterally to the spinal cord. Yet studies in stroke survivors suggest that there may also be changes in neuromodulation at the spinal level, indicative of RS tract influence. We hypothesize that after hemispheric stroke, alterations in the excitability of the RS nuclei affect both sides of the spinal cord, and thereby contribute to increased MN excitability on both paretic/spastic and contralateral sides of stroke survivors, as compared to neurologically intact subjects.

Methods

We estimated stretch reflex thresholds of the biceps brachii (BB) muscle using a position-feedback controlled linear motor to progressively indent the BB distal tendon in both spastic and contralateral limbs of hemispheric stroke survivors and in age-matched intact subjects.

Results

Our previously reported results show a significant difference between reflex thresholds of spastic and contralateral limbs of stroke survivors recorded from BB-medial (p < 0.005) and BB-lateral (p < 0.001). For this study, we report that there is also a significant difference between the reflex thresholds in the contralateral limb of stroke subjects and the dominant arm of intact subjects, again measured from both BB-medial (p < 0.05) and BB-lateral (p < 0.05).

Conclusion

The reduction in stretch reflex thresholds in the contralateral limb of stroke survivors, based here on comparisons with thresholds of intact subjects, suggests an increased MN excitability on contralateral sides of stroke survivors as compared to intact subjects. This in turn supports our contention that RS tract activation, which has bilateral descending influences, is at least partially responsible for increased stretch reflex excitability, post-stroke, as both contralateral and affected sides show increased MN excitability as compared to intact subjects. Still, spasticity, presently diagnosed only on the affected side, with increased MN excitability on the affected side as compared to the contralateral side (our previous study), may be due to a different strongly lateralized pathway, such as the VS tract, which has not been directly tested here. Currently available clinical methods of spasticity assessment, such as the Modified Ashworth Scale, lack the resolution to quantify this phenomenon of a bilateral increase in MN excitability.
The impact of basic vs. enhanced Go NAPSACC on child care centers’ healthy eating and physical activity practices: protocol for a type 3 hybrid effectiveness-implementation cluster-randomized trial
Authors: Vaughn Amber E. , Studts Christina R. , Powell Byron J. , Ammerman Alice S. , Trogdon Justin G. , Curran Geoffrey M. , Hales Derek , Willis Erik , Ward Dianne S.
Published: December 2019

Background

To prevent childhood obesity and promote healthy development, health authorities recommend that child care programs use the evidence-based practices that foster healthy eating and physical habits in children. Go NAPSACC is an intervention shown to improve use of these recommended practices, but it is known to encounter barriers that limit its impact and widespread use.

Methods

This study will use a type 3 hybrid effectiveness-implementation cluster-randomized trial to compare effectiveness and implementation outcomes achieved from Go NAPSACC delivered with a basic or enhanced implementation approach. Participants will include approximately 25 coaches from Child Care Aware of Kentucky (serving four geographic regions), 97 child care centers with a director and teacher from each and two cross-sectional samples of 485 3–4-year-old children (one recruitment at baseline, another at follow-up). Coaches will be randomly assigned to deliver Go NAPSACC using either the basic or enhanced implementation approach. “Basic Go NAPSACC” represents the traditional way of delivering Go NAPSACC. “Enhanced Go NAPSACC” incorporates preparatory and support activities before and during their Go NAPSACC work, which are guided by the Quality Implementation Framework and the Consolidated Framework for Implementation Research. Data will be collected primarily at baseline and post-intervention, with select measures continuing through 6, 12, and 24 months post-intervention. Guided largely by RE-AIM, outcomes will assess change in centers’ use of evidence-based nutrition and physical activity practices (primary, measured via observation); centers’ adoption, implementation, and maintenance of the Go NAPSACC program (assessed via website use); center directors’, teachers’, and coaches’ perceptions of contextual factors (assessed via self-report surveys); children’s eating and physical activity behaviors at child care (measured via observation and accelerometers); and cost-effectiveness (assessed via logs and expense tracking). The hypotheses anticipate that “Enhanced Go NAPSACC” will have greater effects than “Basic Go NAPSACC.”

Discussion

This study incorporates many lessons gleaned from the growing implementation science field, but also offers opportunities to address the field’s research priorities, including applying a systematic method to tailor implementation strategies, examining the processes and mechanisms through which implementation strategies produce their effects, and conducting an economic evaluation of implementation strategies.

Trial Registration

ClinicalTrials.gov, NCT03938103, Registered April 8, 2019
A meta-analysis of the effects of therapeutic hypothermia in adult patients with traumatic brain injury
Authors: Chen Hanbing , Wu Fei , Yang Penglei , Shao Jun , Chen Qihong , Zheng Ruiqiang
Published: December 2019

Purpose

Therapeutic hypothermia management remains controversial in patients with traumatic brain injury. We conducted a meta-analysis to evaluate the risks and benefits of therapeutic hypothermia management in patients with traumatic brain injury.

Methods

We searched the Web of Science, PubMed, Embase, Cochrane (Central) and Clinical Trials databases from inception to January 17, 2019. Eligible studies were randomised controlled trials that investigated therapeutic hypothermia management versus normothermia management in patients with traumatic brain injury. We collected the individual data of the patients from each included study. Meta-analyses were performed for 6-month mortality, unfavourable functional outcome and pneumonia morbidity. The risk of bias was evaluated using the Cochrane Risk of Bias tool.

Results

Twenty-three trials involving a total of 2796 patients were included. The randomised controlled trials with a high quality show significantly more mortality in the therapeutic hypothermia group [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.04 to 1.53, p = 0.02]. Lower mortality in the therapeutic hypothermia group occurred when therapeutic hypothermia was received within 24 h (RR 0.83, 95% CI 0.71 to 0.96, p = 0.01), when hypothermia was received for treatment (RR 0.66, 95% CI 0.49 to 0.88, p = 0.006) or when hypothermia was combined with post-craniectomy measures (RR 0.69, 95% CI 0.48 to 1.00, p = 0.05). The risk of unfavourable functional outcome following therapeutic hypothermia management appeared to be significantly reduced (RR 0.78, 95% CI 0.67 to 0.91, p = 0.001). The meta-analysis suggested that there was a significant increase in the risk of pneumonia with therapeutic hypothermia management (RR 1.48, 95% CI 1.11 to 1.97, p = 0.007).

Conclusions

Our meta-analysis demonstrated that therapeutic hypothermia did not reduce but might increase the mortality rate of patients with traumatic brain injury in some high-quality studies. However, traumatic brain injury patients with elevated intracranial hypertension could benefit from hypothermia in therapeutic management instead of prophylaxis when initiated within 24 h.
Investigating modifications to participant information materials to improve recruitment into a large randomized trial
Authors:   The HPS2-THRIVE Collaborative Group, Haynes Richard , Chen Fang , Wincott Elizabeth , Dayanandan Rejive , Lay Michael J. , Parish Sarah , Bowman Louise , Landray Martin J. , Armitage Jane
Published: December 2019

Background

Large randomized trials are the best method to test the efficacy and safety of treatments expected to have moderate effects. We observed a significant decline in potential participants’ response to mailed invitations to participate in such trials over a 10-year period and investigated possible reasons behind this and potential modifications to the invitation process to mitigate it.

Methods

Participants who declined to participate in the HPS2-THRIVE trial were asked to give a reason. Formal focus groups were conducted to explore the reasons that potential participants might have for not participating. In addition, two embedded randomized comparisons around the timing of provision of the full participant information leaflet (PIL) and its style were conducted during recruitment into this large randomized trial. HPS2-THRIVE is registered at ClinicalTrials.gov (NCT00461630).

Results

The commonest reason given for declining invitations related to mobility and transportation (despite the offer of travel expenses). Both the focus groups and potential participants who declined their invitation indicated concern about side-effects of the treatment (as presented in the PIL) as a reason for declining the invitation. Neither delaying provision of the full PIL until the potential participant attended the trial clinic, nor modifying the style of the PIL improved the proportion of potential participants entering the trial: odds ratio (OR) 1.05 (95% confidence interval (CI) 0.94–1.17) and 1.10 (95% CI 0.94–1.28), respectively. However, modifying the style of the PIL did increase the proportion of participants attending screening appointments (OR 1.17, 95% CI 1.03–1.33).

Conclusions

Many reasons given for not participating in trials are not tractable to individual trials. However, modification of the PIL does show potential to modestly improve participation. If further trials could identify similar simple interventions that were beneficial, their net effects could substantially improve trial participation and facilitate recruitment into large trials.
Effects of combining functional exercises with exercise training on daily physical activities and functionality in patients with COPD: a protocol for a randomized clinical trial
Authors: de Lima Fabiano Francisco , Camillo Carlos Augusto , Grigoletto Isis , Uzeloto Juliana Souza , Vanderlei Franciele Marques , Ramos Dionei , Ramos Ercy Mara Cipulo
Published: December 2019

Introduction

Functional training has been shown to be a viable alternative for the elderly and patients with chronic obstructive pulmonary disease (COPD). However, whether the combination of this type of training with aerobic and resistance training, commonly performed in pulmonary rehabilitation (PR) programs, induces more pronounced effects on daily physical activities and functionality remains unclear. The aims of the study will be to evaluate the short-term and sustained effects of the combination of a functional circuit program with a training program consisting of aerobic and resistance exercise.

Methods

In this randomized controlled trial, patients with COPD will be randomly assigned (1:1:1) to an 8-week training program to follow one of the three a priori defined groups: (I) resistance and aerobic and functional exercises, (II) a conventional program including only resistance and aerobic exercises, or (III) a usual care program. Patients will be evaluated before and upon completion of 8 weeks of training regarding physical activity in daily life (PADL) using an activity monitor (accelerometer), activities of daily living (London Chest Activity of Daily Living), functional exercise capacity (6-minute walk test), and muscle strength (dynamometry). Additionally, the sustained effects of the interventions will be evaluated 22 weeks after commencing the study.

Discussion

The inclusion of a protocol of functional physical training in the training conventionally performed by patients with COPD as an alternative to increase PADL and functionality may provide subsidies for the treatment of these patients, representing an advance and impacting on the physical training of patients with COPD.

Trial registration

Brazilian Clinical Trials Registry (ReBEC) ID: RBR-3zmh3r. Registered: March 7, 2018.
Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs
Authors: de Moel Emma C. , Rech Jürgen , Mahler Michael , Roth Johannes , Vogl Thomas , Schouffoer Anne , Goekoop Robbert J. , Huizinga Tom W. J. , Allaart Cornelia F. , Toes René E. M. , Schett Georg , van der Woude Diane
Published: December 2019

Objective

To investigate whether calprotectin (S100A8/A9 or MRP8/14), an inflammatory complex released by monocytes, could indicate residual subclinical inflammation in rheumatoid arthritis (RA) patients who are in stable remission on disease-modifying anti-rheumatic drugs (DMARDs) and serve as a marker for disease flare after DMARD tapering.

Methods

We used data from two trials. Patients from the IMPROVED study had early (< 2 years) RA, and when they achieved disease activity score remission (DAS44 < 1.6), they stopped methotrexate to attempt drug-free remission. Patients from the RETRO study had established RA in stable remission (DAS28 < 2.6) and either tapered by 50% or stopped (biological or conventional) DMARDs. Circulating calprotectin at the tapering time point was determined by ELISA, and its predictive value for flare (loss of remission) within 12 months of DMARD tapering/stopping was determined.

Results

In both IMPROVED (n = 104) and RETRO (n = 57), patients that flared within 12 months had higher calprotectin at the moment of DMARD tapering/stopping. Twofold higher calprotectin at the moment of DMARD tapering/stopping was associated with an increased risk (odds ratio) of flare of 1.07 (95% CI 0.98–1.18,p = 0.14) in the IMPROVED and 3.62 (95% CI 1.76–7.46,p < 0.001) in the RETRO. Correcting for clinical predictors of flare (DAS at study inclusion, anti-CCP2 positivity, gender) did not change these estimates. The area under the receiver operating curve of calprotectin levels for predicting flare within 12 months was 0.63 (95% CIs 0.51–0.76) in the IMPROVED study and 0.80 (95% CIs 0.69 to 0.92) in the RETRO study.

Conclusion

Circulating calprotectin levels in RA patients in remission on DMARDs are higher in patients that will flare upon DMARD tapering/stopping. Since the differences between the cohorts precluded definitive conclusions, more research is needed to determine whether calprotectin has prognostic value in predicting flare after attempting drug tapering in RA.

Trial registration

IMPROVED,ISRCTN11916566. RETRO,2009-015740-42.
Effect of synbiotic bread containing lactic acid on glycemic indicators, biomarkers of antioxidant status and inflammation in patients with type 2 diabetes: a randomized controlled trial
Authors: Ghafouri Atie , Zarrati Mitra , Shidfar Farzad , Heydari Iraj , Shokouhi Shoormasti Raheleh , Eslami Omid
Published: December 2019

Background

The aim of this randomized, double-blinded, controlled trial was to investigate the effect of daily consumption of a synbiotic bread containing lactic acid on glycemic status, antioxidant biomarkers and inflammation in patients with type 2 diabetes (T2D).

Methods

T2D patients, aged 20 to 60 years, were randomly assigned to consume synbiotic + lactic acid (n = 30), synbiotic (n = 30), lactic acid (n = 30), or control (n = 30) bread for 8 weeks. Patients consumed bread 3 times a day in a 40 g package for a total of 120 g/day. Glycemic status, antioxidant capacity, and serum hs-CRP were assessed before and after the intervention.

Results

Of a total of 120 patients that were included in the study, 100 completed the trial. In the adjusted analysis, it was found that consumption of synbiotic + lactic acid bread caused a significant decrease in HbA1c compared to the control bread (− 0.41 ± 0.33 vs 0.004 ± 0.10%, respectively; P < 0.001), while it significantly increased serum superoxide dismutase (SOD) (0.87 ± 1.14 vs. 0.18 ± 0.85 mmol/L, P = 0.02). Also, changes in glutathione peroxidase (GSH-Px) were significantly higher following the consumption of synbiotic + lactic acid bread than lactic acid bread. However, it had no significant effect on fasting plasma glucose, serum insulin, and total antioxidant capacity.

Conclusion

Overall, daily consumption of a synbiotic bread containing lactic acid for 8 weeks had beneficial effects on HbA1c, SOD, and GSH-Px among T2D patients.

Trial registration This study was registered in Iranian Registry of Clinical Trials with number: IRCT201505242709N33 (Registration date: 2015-11-23, http://www.irct.ir/trial/2544)
Attitudes and behavior related to performance-enhancing substance use among elite Saudi football players
Authors: Al Ghobain Mohammed
Published: December 2019

Objective

To investigate the attitudes, beliefs and behavior related to performance enhancing substances (PES) use in elite Saudi football players.

Method

A cross-sectional survey was conducted. Using a systematic random sample of elite Saudi male football players, the standard World Anti-doping Agency (WADA) Social Science Research Package questionnaire was distributed to 408 players.

Results

The overall prevalence rate of PES use was 3.9%, with the overall prevalence rate of doping susceptibility 17.1%. PES use or doping susceptibility is strongly correlated but negatively associated with morality and cheating measures (p <  0.011, the estimate is − 0.139), threat or deterrence appraisal (p <  0.001, the estimate is − 0.301) and beliefs about the reference group’s endorsement (p < 0.001, the estimate is − 0.213) but not with legitimacy perceptions (p = 0.513) and beliefs about the benefits of doping (p = 0.678). The strongest relationship was found between threat or deterrence appraisal (p < 0.001), and beliefs about the reference group’s endorsement of PES use (p < 0.001).

Conclusion

Morality and cheating measures, threat or deterrence appraisal and beliefs about the reference group’s endorsement are the main predictors for PES use in Saudi Arabia.
Isolation and identification of Streptococcus suis from sick pigs in Bali, Indonesia
Authors: Besung I Nengah Kerta , Suarjana I Gusti Ketut , Agustina Kadek Karang , Winaya Ida Bagus Oka , Soeharsono Hamong , Suwiti Ni Ketut , Mahardika Gusti Ngurah
Published: December 2019

Objective

Streptococcus suis (S. suis) is a causative agent for various syndromes in pigs. It can be transmitted to humans with typical symptoms of meningitis and death. Although human infections have been confirmed at Bali Referral Hospital, Indonesia, since 2014, the bacteria have not been isolated from pigs. Here, we provide confirmation of the presence of the bacteria in sick pigs in the province.

Results

Streptococcus suis was confirmed in 8 of 30 cases. The final confirmation was made using PCR and sequencing of the glutamate dehydrogenase (GDH) and recombination/repair protein (recN) gene fragments. Upon PCR serotyping, two were confirmed to be serotype 2 or 1/2. Prominent histopathological lesions of confirmed cases were meningitis, endocarditis, pericarditis, bronchopneumonia, enteritis and glomerulonephritis. The dominant inflammatory cells were neutrophils and macrophages. Further research is needed to understand the risk factors for human infection. Community awareness on the risk of contracting S. suis and vaccine development are needed to prevent human infections.
Expression of a recombinant bacterial l-asparaginase in human cells
Authors: Dantas Raquel Caminha , Caetano Ludmilla Freire , Torres Ariany Lima Sousa , Alves Matheus Soares , Silva Emanuelly Thays Muniz Figueiredo , Teixeira Louhanna Pinheiro Rodrigues , Teixeira Daniel Câmara , de Azevedo Moreira Renato , Fonseca Marcela Helena Gambim , Gaudêncio Neto Saul , Martins Leonardo Tondello , Furtado Gilvan Pessoa , Tavares Kaio Cesar Simiano
Published: December 2019

Objective

l-Asparaginase (ASNase) is an enzyme used in the treatment of acute lymphoblastic leukemia (ALL). As the therapeutic ASNases has bacterial origin, severe side effects are associated with its use, among them hypersensitivity and inactivation of the enzyme. In this context, the objective of this work was to produce a recombinant ASNase of bacterial origin in human cells in order to determine the presence and consequences of potential post-translational modifications on the enzyme.

Results

Recombinant ASNase was expressed in human cells with a molecular weight of 60 kDa, larger than in Escherichia coli, which is 35 kDa. N-glycosylation analysis demonstrated that the increased molecular weight resulted from the addition of glycans to the protein by mammalian cells. The glycosylated ASNase presented in vitro activity at physiological pH and temperature. Given that glycosylation can act to reduce antigenicity by masking protein epitopes, our data may contribute to the development of an alternative ASNase in the treatment of ALL in patients who demonstrate side effects to currently marketed enzymes.
Wharton’s jelly mesenchymal stem cell-based or umbilical vein endothelial cell-based serum-free coculture with cytokines supports the ex vivo expansion/maintenance of cord blood hematopoietic stem/progenitor cells
Authors: Li Qiuyang , Zhao Dewan , Chen Qiang , Luo Maowen , Huang Jingcao , Yang Cao , Wang Fangfang , Li Wenxian , Liu Ting
Published: December 2019

Background

The umbilical cord blood (UCB) has been widely accepted as an alternative source of hematopoietic stem/progenitor cells (HSPCs) for transplantation, and its use in adults is still restricted because of low absolute numbers. To overcome this obstacle, expansion of UCB-HSPCs under feeder cell-based coculture is a promising possibility. In this study, we explored UCB-CD34+ cells ex vivo expansion using Wharton’s jelly mesenchymal stem cells (WJ-MSCs) or umbilical vein endothelial cells (UVECs) as feeder layer-based serum-free coculture system with a cocktail of cytokines.

Methods

UCB-CD34+ cells were cultured in five different coculture conditions composed of umbilical cord stromal cells (WJ-MSCs or UVECs) with or without a cocktail of cytokines (SCF, FLT3L, and TPO). The cultured cells were harvested at day 10 and analyzed for phenotypes and functionalities, including total nuclear cells (TNCs), CD34+ cells, CD34+CD38− cells, colony-forming unit (CFU) for committed progenitors, and long-term culture initiating cells (LTC-ICs) for HSPCs.

Results

Our work showed the numbers of TNC cells, CD34+ cells, and CD34+CD38− cells were expanded under five coculture conditions, and the feeder layer-based cocultures further promoted the expansion. The numbers of colonies of CFU-GM, CFU-E/BFU-E, and CFU-GEMM in the cocultures with cytokines were significantly higher than their counterparts at day 0 (p < 0.05), while no significant difference (p > 0.05) in those without the addition of cytokines. The numbers of LTC-ICs were increased both under the WJ-MSCs and UVECs with cytokine cocultures, but only in the UVECs group showed a significant difference (p < 0.05), and were decreased under conditions without cytokine (p < 0.05).

Conclusion

Our data demonstrate that both WJ-MSCs and UVECs as feeder layer could efficiently support the expansion of UCB-CD34+ cells in synergy with SCF, FLT3L, and TPO under serum-free culture condition. The UVECs combined with the 3GF cytokine cocktail could maintain the growth of LTC-ICs derived from UCB-CD34+ cells and even expand to some extent.