bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of an influenza information pamphlet on vaccination uptake among Polish pupils in Edinburgh, Scotland and the role of social media in parental decision making
Authors: Bielecki K. , Craig J. , Willocks L. J. , Pollock K. G. , Gorman D. R.
Published: September 2020

Background

In Edinburgh, Scotland, lower influenza vaccine uptake has been observed in primary school children in the Polish community.

Methods

To address this disparity, the Polish-language version of the NHS Health Scotland influenza information pamphlet was updated and distributed in 2018 to all identified Polish pupils attending three pilot schools. The impact of the revised pamphlet was evaluated by examining changes in vaccine uptake in these schools as compared to a control group of schools, and a questionnaire was issued to all Polish parents in the pilot schools to explore their opinions of the pamphlet and preferred sources of immunisation information.

Results

On average uptake was 7.4% (95% CI 1.0–13.8%, p < 0.05) higher in the three pilot schools in which the Polish-language pamphlet was distributed (28.7%) than control schools (21.3%). The questionnaire feedback was that 37.3% of respondents felt better-informed about the influenza vaccine following the pamphlet. The respondents reported that the most important information source in deciding whether to vaccinate is previous experience. Healthcare professionals were ranked lower in importance when making a decision. Parents, who refused consent (n = 65) were more likely to source information from social media, friends and family, and Polish websites compared with those who consented (n = 45).

Conclusions

These findings suggest that issuing new Polish health literature was associated with a large increase in consent form return rate and a modest increase in uptake of the influenza vaccine by Polish pupils in the pilot schools. Social media and Polish websites were found to have a greater influence over Polish parents’ decision to immunise than UK healthcare staff and health authority information. Intensive effort is required to encourage parents towards information sources where more accurate pro-vaccination messages can be promulgated by national health services and independent expert groups. The role of social media for migrant communities requires careful consideration, especially for vaccine programmes not delivered in their country of birth.
Targeted vaccination campaigns of teenagers after two clusters of B invasive meningococcal disease in Brittany, France, 2017
Authors: Pivette Mathilde , Taha Muhamed-Kheir , Barret Anne-Sophie , Polard Elisabeth , Hautier Marie-Bernadette , Dufour Jean-Benoît , Faisant Marlène , King Lisa Antoinette , Antona Denise , Levy-Bruhl Daniel , Tillaut Hélène , Scanff Alexandre , Morival Camille , Aranda Grau José-Hector , Guillaumot Pierre , Gagnière Bertrand
Published: September 2020

Background

In December 2016, three cases of serogroup B invasive meningococcal disease, including two children from the same middle school (11 to 15 years old pupils), occurred in the department (administrative district) Côtes-d’Armor (Brittany, France). They were infected by a rare strain (B:P1.7–2,4:F5–9:cc162), covered by the 4CMenB vaccine (Bexsero®). Four months later, two cases due to the same strain occurred in a high school in the same area (15 to 19 years old students). In accordance with French recommendations, vaccination was proposed to students of both schools and to all individuals aged 11–19 years living or studying in the hyperendemic area. We describe these vaccination campaigns, from the alert to the impact evaluation.

Methods

The target population included 8884 people: 579 in the middle school, 2007 in the high school and 6298 in the community. In both schools, vaccination sessions were organized directly on site. In the community, teenagers were vaccinated by general practitioners. The vaccination campaign took place from May to October 2017. An active pharmacovigilance follow-up was set up to document adverse effects of the vaccine.

Results

Considering the whole target population, the vaccination coverage was estimated at 43% for 1 dose and 34% for 2 doses. Higher vaccination coverage was observed in the schools (79% in the middle school and 42% in the high school for 2 doses) than in the community (27% for 2 doses). The reported adverse effects were consistent with the safety profile of the vaccine and no severe adverse effect was reported.

Conclusions

This vaccination campaign was the third one implemented with Bexsero® in France and constitutes a reproducible approach for future targeted vaccination campaigns. No additional cases of the same strain have occurred since the end of the campaigns in the area.
Classifications of good versus poor outcome following knee arthroplasty should not be defined using arbitrary criteria
Authors: Riddle Daniel L. , Dumenci Levent
Published: September 2020

A recently published paper by te Molder and colleagues in BMC Musculoskeletal Disorders confirmed prior reports indicating that definitions of good versus poor outcome cutoff scores for relevant knee arthroplasty outcomes including pain and function are heterogeneous and that this heterogeneity prevents generalizable inferences. In this Correspondence, we highlight an additional and, in our view, a more important problem with the substantial literature on this topic. There also is high homogeneity in that all studies relied on arbitrarily defined cutoff scores to differentiate good versus poor outcome. We discuss this problem and propose a method to avoid repeating the same problem in future studies designed to group patients into those with good versus those with poor outcome following knee arthroplasty.
Clinical indicators to identify neuropathic pain in low back related leg pain: a modified Delphi study
Authors: Mistry Jai , Falla Deborah , Noblet Tim , Heneghan Nicola R. , Rushton Alison
Published: September 2020

Background

Neuropathic pain (NP) is common in patients presenting with low back related leg pain. Accurate diagnosis of NP is fundamental to ensure appropriate intervention. In the absence of a clear gold standard, expert opinion provides a useful methodology to progress research and clinical practice. The aim of this study was to achieve expert consensus on a list of clinical indicators to identify NP in low back related leg pain.

Methods

A modified Delphi method consisting of three rounds was designed in accordance with the Conducting and Reporting Delphi Studies recommendations. Recruitment involved contacting experts directly and through expressions of interest on social media. Experts were identified using pre-defined eligibility criteria. Priori consensus criteria were defined for each round through descriptive statistics. Following completion of round 3 a list of clinical indicators that achieved consensus were generated.

Results

Thirty-eight participants were recruited across 11 countries. Thirty-five participants completed round 1 (92.1%), 32 (84.2%) round 2 and 30 (78.9%) round 3. Round 1 identified consensus (Kendall’s W coefficient of concordance 0.456; p < 0.001) for 10 clinical indicators out of the original 14, and 9 additional indicators were added to round 2 following content analysis of qualitative data. Round 2 identified consensus (Kendall’s W coefficient of concordance 0.749; p < 0.001) for 10 clinical indicators out of 19, and 1 additional indicator was added to round 3. Round 3 identified consensus for 8 indicators (Kendall’s W coefficient of concordance 0.648; p < 0.001). Following completion of the third round, an expert derived consensus list of 8 items was generated. Two indicators; pain variously described a burning, electric shock like and/or shooting into leg and pain in association with other neurological symptoms (e.g. pins and needles, numbness, weakness), were found to have complete agreement amongst expert participants.

Conclusions

Good agreement was found for the consensus derived list of 8 clinical indicators to identify NP in low back related leg pain. This list of indicators provide some indication of the criteria upon which clinicians can identify a NP component to low back related leg pain; further research is needed for stronger recommendations to be made.
Complications to 6 months following total hip or knee arthroplasty: observations from an Australian clinical outcomes registry
Authors: Heo Sung Mu , Harris Ian , Naylor Justine , Lewin Adriane M.
Published: September 2020

Background

Total hip and total knee arthroplasty (THA/TKA) are increasing in incidence annually. While these procedures are effective in improving pain and function, there is a risk of complications.

Methods

Using data from an arthroplasty registry, we described complication rates including reasons for reoperation and readmission from the acute period to six months following THA and TKA in an Australian context. Data collection at 6 months was conducted via telephone interview, and included patient-reported complications such as joint stiffness, swelling and paraesthesia. We used logistic regression to identify risk factors for complications.

Results

In the 8444 procedures included for analysis, major complications were reported by 9.5 and 14.4% of THA and TKA patients, respectively, whilst minor complications were reported by 34.0 and 46.6% of THA and TKA patients, respectively. Overall complications rates were 39.7 and 53.6% for THA and TKA patients, respectively. In THA patients, factors associated with increased risk for complications included increased BMI, previous THA and bilateral surgery, whereas in TKA patient factors were heart disease, neurological disease, and pre-operative back pain and arthritis in a separate joint. Female gender and previous TKA were identified as protective factors for minor complications in TKA patients.

Conclusion

We found moderate rates of major and high rates of minor postoperative complications following THA and TKA in Australia and have identified several patient factors associated with these complications. Efforts should be focused on identifying patients with higher risk and optimising pre- and post-operative care to reduce the rates of these complications.
Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cancer
Authors: Lee Eun Hye , Chun So Young , Kim Bomi , Yoon Bo Hyun , Lee Jun Nyung , Kim Bum Soo , Yoo Eun Sang , Lee Sangkyu , Song Phil Hyun , Kwon Tae Gyun , Ha Yun-Sok
Published: September 2020

Background

Bladder cancer (BC) is one of the most common malignancies of the urinary tract. The role of transient receptor potential melastatin 7 (TRPM7) in BC remains unclear. The aim of this study was to investigate the function and signal transduction pathway of TRPM7 in BC.

Methods

T24 and UMUC3 cells were used to evaluate the molecular mechanism of TRPM7 by immunoblot analysis. Small interfering RNA was used to knockdown TRPM7, and the effect of silencing TRPM7 was studied by wound healing, migration, and invasion assays in T24 and UMUC3 cells. Xenograft model study was obtained to analyze the effect of TRPM7 inhibition in vivo.

Results

Silencing of TRPM7 decreased the migration and invasion ability of T24 and UMUC3 cells. The phosphorylation of Src, Akt, and JNK (c-Jun N-terminal kinase) was also suppressed by TRPM7 silencing. Src, Akt, and JNK inhibitors effectively inhibited the migration and invasion of T24 and UMUC3 cells. In addition, the TRPM7 inhibitor, carvacrol, limited the tumor size in a xenograft model.

Conclusion

Our data reveal that TRPM7 regulates the migration and invasion of T24 and UMUC3 cells via the Src, Akt, and JNK signaling pathway. Therefore, TRPM7 suppression could be a potential treatment for BC patients.
The profile of hematinic deficiencies in patients with oral lichen planus: a case-control study
Authors: Bao Zhe-xuan , Yang Xiao-wen , Shi Jing , Wang Yu-feng
Published: September 2020

Background

Oral lichen planus (OLP) is a relatively common mucocutaneous disorder, and its causative factors and pathogenesis are not fully understood. Existing studies on the association between hematinic deficiencies and OLP are limited and inconsistent. The aim of this study was to assess the hematinic deficiencies in a cohort of OLP patients and evaluate the correlation between hematinic deficiencies and OLP.

Methods

A total of 236 OLP patients and 226 age-and-gender-matched healthy controls were enrolled in this study. The levels of hemoglobin (Hb), serum folate, vitamin B12 and ferritin were measured and compared between OLP patients and healthy controls. An REU (reticular/hyperkeratotic, erosive/erythematous, ulcerative) scoring system was adopted and compared between the OLP patients with and without hematinic deficiencies. The correlation between hematinic deficiencies and OLP was analyzed.

Results

The frequencies of serum ferritin and vitamin B12 deficiency in OLP patients were both significantly higher than those of the healthy controls. According to gender and age, the profiles of hematinic deficiencies in OLP patients were significantly different. As for the REU score, no significant difference existed between OLP patients with and without hematinic deficiencies. Both serum ferritin deficiency and serum vitamin B12 deficiency were significantly correlated with OLP.

Conclusions

The present study suggested a significant association between hematinic deficiencies and OLP. Iron, folate, and vitamin B12 levels in OLP patients should be monitored routinely. Further studies are warranted to explore the interactions between OLP and hematinic deficiencies.
A Danish version of the oral health impact profile-14 (OHIP-14): translation and cross-cultural adaptation
Authors: Gera Arwa , Cattaneo Paolo M. , Cornelis Marie A.
Published: September 2020

Background

The Oral Health Impact Profile-14 (OHIP-14) questionnaire assesses quality of life related to people’s perception of oral disorders on their well-being. However, a translated and validated Danish version of OHIP-14 is not yet available.

The purpose of this pilot study was to translate and cross-culturally adapt the English version of the OHIP-14 into Danish (OHIP-14-DK). In addition, to assess its content and face validity, internal consistency and test-retest reliability.

Methods

The English version of OHIP-14 was translated into Danish following a standard protocol of cross-cultural adaptation. Stages I-IV: translation phase to generate a pre-final version “OHIP-14-DK”. Stage V: pre-testing phase. A random sample of 22 orthodontic patients (mean age 24.7 years, SD ±14.8; 14 females, 8 males) were selected at the Section of Orthodontics, Aarhus University, Denmark. All patients self-completed the OHIP-14-DK and were then interviewed to assess its content and face validity. Internal consistency was assessed with Cronbach’s alpha coefficients. All patients completed the same questionnaire again at a one-week interval. Test-retest reliability was assessed using Spearman’s correlation coefficient and intra-class correlation coefficient (ICC).

Results

The initial and back translations were very similar: the OHIP-14-DK proved to have a good level of equivalence with no translation errors or deviations. Furthermore, the OHIP-14-DK seemed well-adapted to Danish culture and was understood by individuals down to 12 years of age. Pre-testing demonstrated good face and content validity; interviews had a response rate of 100% and confirmed that each item was understandable without inducing reluctance or hesitation. Thus, responses were related to their corresponding item. Therefore, no final adjustments were required for the pre-tested version. Cronbach’s alpha for the OHIP-14-DK subscales fell in the 0.75–0.84 range, indicating an adequate-to-good internal consistency. Spearman’s correlation coefficient for the OHIP-14-DK total score was 0.77. The ICC for the OHIP-14-DK total score was 0.91.

Conclusions

The OHIP-14-DK seems well adapted to Danish culture, proved to be face and content valid and also showed good internal consistency and excellent reliability. However, its psychometric properties still need to be tested.

Study registration

Not applicable
Examining determinants of gender attitudes: evidence among Tanzanian adolescents
Authors: Palermo Tia , Chzhen Yekaterina , Balvin Nikola , Kajula Lusajo ,   Tanzania Adolescent Cash Plus Evaluation Team, Palermo Tia , Groppo Valeria , de Hoop Jacobus , Kajula Lusajo , Prencipe Leah , Waidler Jennifer , Choumert Nkolo Johanna , Mitti Respichius , Sivewright Nathan , Leuveld Koen , Munanka Bhoke , Luchemba Paul , Mnyawami Lukongo Tumpe , Mulokozi Aroldia , Gilbert Ulrike , Quarles van Ufford Paul , Le Kirkegaard Rikke , Eetaama Frank
Published: September 2020

Background

The shaping of gender beliefs and attitudes in early adolescence affects the way young people internalize and self-enforce prevalent notions of masculinity and femininity, with lifelong consequences for sexual and reproductive health. This cross-sectional study examines determinants of gender attitudes among some of the poorest and most vulnerable adolescents in Tanzania using an ecological model.

Methods

Data come from baseline interviews with 2458 males and females aged 14–19 years conducted as part of a larger impact evaluation. Structural equation models are used to examine how factors at the community-, household-, and individual-levels influence gender attitudes in the four domains measured by the Gender Equitable Men (GEM) Scale (i.e. violence, sexual relationships, reproductive health and disease prevention, and domestic chores and daily life).

Results

A structural equation model of the four latent domains of the GEM scale regressed on individual, social-interactional and structural level characteristics indicated that secondary school attendance was associated with more equitable gender attitudes, while females held less equitable attitudes than males in the sample. Having had sexual intercourse was associated with more gender equitable attitudes among females, but the reverse was true among males.

Conclusions

Addressing gender inequity requires understanding gender socialisation at the socio-interactional level. As females had more inequitable gender attitudes than males in the study, a special emphasis on highlighting the rights of women to girls should be considered. This study will inform future analysis of programme impacts on gender attitudes and sexual and reproductive health.
Qualitative evaluation of the general practitioner chronic non-communicable diseases training programme
Authors: Zhang Chunyu , Fang Fang , Peng Mingqiang , Zhao Ying , Liu Ruixue , Jia Cunbo
Published: September 2020

Background

In China, general practitioners have limited ability to provide care for common chronic non-communicable diseases because they lack postgraduate training. In an attempt to improve general practitioners’ skills in this regard, the present authors previously launched the Chronic Non-Communicable Diseases Training Programme. The present study aims to evaluate the effectiveness of this programme.

Methods

Thirty-nine trainee general practitioners who participated in the programme underwent semi-structured interviews, which explored how they performed the training, what they achieved from the programme, and their suggestions for future programmes. The interview data were analysed using a thematic analysis approach.

Results

Under the guidance of supervisors, the thirty-nine trainee general practitioners completed the structured but individualised training plan, which comprised a four-day basic theory class, 3 months practising in a ward, and 6 months assisting in an outpatient clinic. They reported an improvement in their ability to provide care for chronic non-communicable diseases and perform two-way referral, as well as their communication with patients. They also reported that, since returning to their communities, they had become more confident, were building better relationships with their patients, and had changed their clinic behaviours from copying prescriptions to making medical decisions independently. Their principal suggestion for the training programme was to alter the order of the training, as they preferred to practice in the ward before assisting in the outpatient clinic.

Conclusion

The course comprised a learner-centred, practice- and apprenticeship-based, general-practitioner training programme. Given the participants’ progress and the beneficial effects of the programme reported in the interview data, it appears to be worthwhile to extend the General Practitioner Chronic Non-Communicable Diseases Training Programme.
Semi-supervised method for image texture classification of pituitary tumors via CycleGAN and optimized feature extraction
Authors: Zhu Hong , Fang Qianhao , Huang Yihe , Xu Kai
Published: September 2020

Background

Accurately determining the softness level of pituitary tumors preoperatively by using their image textures can provide a basis for surgical options and prognosis. Existing methods for this problem require manual intervention, which could hinder the efficiency and accuracy considerably.

Methods

We present an automatic method for diagnosing the texture of pituitary tumors using unbalanced sequence image data. Firstly, for the small sample problem in our pituitary tumor MRI image dataset where T1 and T2 sequence data are unbalanced (due to data missing) and under-sampled, our method uses a CycleGAN (Cycle-Consistent Adversarial Networks) model for domain conversion to obtain fully sampled MRI spatial sequence. Then, it uses a DenseNet (Densely Connected Convolutional Networks)-ResNet(Deep Residual Networks) based Autoencoder framework to optimize the feature extraction process for pituitary tumor image data. Finally, to take advantage of sequence data, it uses a CRNN (Convolutional Recurrent Neural Network) model to classify pituitary tumors based on their predicted softness levels.

Results

Experiments show that our method is the best in terms of efficiency and accuracy (91.78%) compared to other methods.

Conclusions

We propose a semi-supervised method for grading pituitary tumor texture. This method can accurately determine the softness level of pituitary tumors, which provides convenience for surgical selection and prognosis, and improves the diagnostic efficiency of pituitary tumors.
Determinants of antenatal care dropout among mothers who gave birth in the last six months in BAHIR Dar ZURIA WOREDA community; mixed designs
Authors: Bekele Yibeltal Alemu , Tafere Tadesse Ejigu , Emiru Amanu Aragaw , Netsere Henok Biresaw
Published: September 2020

Background

Antenatal care is the care provides for a pregnant mother to improve the health of the mother and her baby. But in the World including Ethiopia still, mothers do not receive the required number of antenatal care visits. Therefore, the main aim of this study was to identify determinants of Antenatal care visit dropout in Bahir Dar Zuria Woreda North West Ethiopia.

Methods

The study was community-based unmatched case-control study that employed both quantitative and qualitative data. For the quantitative part, 134 cases and 266 controls (total 400) women who gave births in the last six months prior to the study in Bahir Dar Zuria Woreda were enrolled. Data were collected through face to face interviews from March 1 to 30, 2018 using a structured questionnaire. Bivariate and multivariate analysis was used. 95% confidence interval and P-value was used to measure the level of significance. For the qualitative part, six FGDs were conducted and open code software was used for the analysis of the data. The finding was narrated by triangulating with the quantitative findings.

Result

Being far distance (AOR 7.26; 95% CI 4.23, 23.01), not having a companion (AOR 3.49; 95% CI; 2.39, 8.44), lack of knowledge (AOR 2.57; 95% CI; 1.25, 5.28), poor wealth index (AOR; 3.36, 95% CI 1.71, 6.62) and not developing a danger sign (AOR 2.18; 95% CI 2.28, 7.64) were predictors of ANC dropout. In addition to this, in the qualitative finding, the socio-culture of the community, attitudes, experience, and perception of the existing services and service provisions were also determinants of ANC drop out.

Conclusion

Socio-cultural, economic, accessibility, and individual factors were determinants of ANC visit drop out. In addition, the behavior of the professional, the mother understands of the existing services, and their perception about ANC influenced ANC dropout.
Novel developmental bases for the evolution of hypobranchial muscles in vertebrates
Authors: Kusakabe Rie , Higuchi Shinnosuke , Tanaka Masako , Kadota Mitsutaka , Nishimura Osamu , Kuratani Shigeru
Published: September 2020

Background

Vertebrates are characterized by possession of hypobranchial muscles (HBMs). Cyclostomes, or modern jawless vertebrates, possess a rudimentary and superficial HBM lateral to the pharynx, whereas the HBM in jawed vertebrates is internalized and anteroposteriorly specified. Precursor cells of the HBM, marked by expression of Lbx1, originate from somites and undergo extensive migration before becoming innervated by the hypoglossal nerve. How the complex form of HBM arose in evolution is relevant to the establishment of the vertebrate body plan, but despite having long been assumed to be similar to that of limb muscles, modification of developmental mechanisms of HBM remains enigmatic.

Results

Here we characterize the expression of Lbx genes in lamprey and hagfish (cyclostomes) and catshark (gnathostome; jawed vertebrates). We show that the expression patterns of the single cyclostome Lbx homologue, Lbx-A, do not resemble the somitic expression of mammalian Lbx1. Disruption of Lbx-A revealed that LjLbx-A is required for the formation of both HBM and body wall muscles, likely due to the insufficient extension of precursor cells rather than to hindered muscle differentiation. Both homologues of Lbx in the catshark were expressed in the somitic muscle primordia, unlike in amniotes. During catshark embryogenesis, Lbx2 is expressed in the caudal HBM as well as in the abdominal rectus muscle, similar to lamprey Lbx-A, whereas Lbx1 marks the rostral HBM and pectoral fin muscle.

Conclusions

We conclude that the vertebrate HBM primarily emerged as a specialized somatic muscle to cover the pharynx, and the anterior internalized HBM of the gnathostomes is likely a novelty added rostral to the cyclostome-like HBM, for which duplication and functionalization of Lbx genes would have been a prerequisite.
Some like it hot: population-specific adaptations in venom production to abiotic stressors in a widely distributed cnidarian
Authors: Sachkova Maria Y. , Macrander Jason , Surm Joachim M. , Aharoni Reuven , Menard-Harvey Shelcie S. , Klock Amy , Leach Whitney B. , Reitzel Adam M. , Moran Yehu
Published: September 2020

Background

In cnidarians, antagonistic interactions with predators and prey are mediated by their venom, whose synthesis may be metabolically expensive. The potentially high cost of venom production has been hypothesized to drive population-specific variation in venom expression due to differences in abiotic conditions. However, the effects of environmental factors on venom production have been rarely demonstrated in animals. Here, we explore the impact of specific abiotic stresses on venom production of distinct populations of the sea anemone Nematostella vectensis (Actiniaria, Cnidaria) inhabiting estuaries over a broad geographic range where environmental conditions such as temperatures and salinity vary widely.

Results

We challenged Nematostella polyps with heat, salinity, UV light stressors, and a combination of all three factors to determine how abiotic stressors impact toxin expression for individuals collected across this species’ range. Transcriptomics and proteomics revealed that the highly abundant toxin Nv1 was the most downregulated gene under heat stress conditions in multiple populations. Physiological measurements demonstrated that venom is metabolically costly to produce. Strikingly, under a range of abiotic stressors, individuals from different geographic locations along this latitudinal cline modulate differently their venom production levels.

Conclusions

We demonstrate that abiotic stress results in venom regulation in Nematostella. Together with anecdotal observations from other cnidarian species, our results suggest this might be a universal phenomenon in Cnidaria. The decrease in venom production under stress conditions across species coupled with the evidence for its high metabolic cost in Nematostella suggests downregulation of venom production under certain conditions may be highly advantageous and adaptive. Furthermore, our results point towards local adaptation of this mechanism in Nematostella populations along a latitudinal cline, possibly resulting from distinct genetics and significant environmental differences between their habitats.
Estimating indirect mortality impacts of armed conflict in civilian populations: panel regression analyses of 193 countries, 1990–2017
Authors: Jawad Mohammed , Hone Thomas , Vamos Eszter P. , Roderick Paul , Sullivan Richard , Millett Christopher
Published: September 2020

Background

Armed conflict can indirectly affect population health through detrimental impacts on political and social institutions and destruction of infrastructure. This study aimed to quantify indirect mortality impacts of armed conflict in civilian populations globally and explore differential effects by armed conflict characteristics and population groups.

Methods

We included 193 countries between 1990 and 2017 and constructed fixed effects panel regression models using data from the Uppsala Conflict Data Program and Global Burden of Disease study. Mortality rates were corrected to exclude battle-related deaths. We assessed separately four different armed conflict variables (capturing binary, continuous, categorical, and quintile exposures) and ran models by cause-specific mortality stratified by age groups and sex. Post-estimation analyses calculated the number of civilian deaths.

Results

We identified 1118 unique armed conflicts. Armed conflict was associated with increases in civilian mortality—driven by conflicts categorised as wars. Wars were associated with an increase in age-standardised all-cause mortality of 81.5 per 100,000 population (β 81.5, 95% CI 14.3–148.8) in adjusted models contributing 29.4 million civilian deaths (95% CI 22.1–36.6) globally over the study period. Mortality rates from communicable, maternal, neonatal, and nutritional diseases (β 51.3, 95% CI 2.6–99.9); non-communicable diseases (β 22.7, 95% CI 0.2–45.2); and injuries (β 7.6, 95% CI 3.4–11.7) associated with war increased, contributing 21.0 million (95% CI 16.3–25.6), 6.0 million (95% CI 4.1–8.0), and 2.4 million deaths (95% CI 1.7–3.1) respectively. War-associated increases in all-cause and cause-specific mortality were found across all age groups and both genders, but children aged 0–5 years had the largest relative increases in mortality.

Conclusions

Armed conflict, particularly war, is associated with a substantial indirect mortality impact among civilians globally with children most severely burdened.
Aspirin and other non-steroidal anti-inflammatory drugs and depression, anxiety, and stress-related disorders following a cancer diagnosis: a nationwide register-based cohort study
Authors: Hu Kejia , Sjölander Arvid , Lu Donghao , Walker Adam K. , Sloan Erica K. , Fall Katja , Valdimarsdóttir Unnur , Hall Per , Smedby Karin E. , Fang Fang
Published: September 2020

Background

Cancer patients have a highly increased risk of psychiatric disorders following diagnosis, compared with cancer-free individuals. Inflammation is involved in the development of both cancer and psychiatric disorders. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the subsequent risk of psychiatric disorders after cancer diagnosis is however unknown.

Methods

We performed a cohort study of all patients diagnosed with a first primary malignancy between July 2006 and December 2013 in Sweden. Cox proportional hazards models were used to assess the association of NSAID use during the year before cancer diagnosis with the risk of depression, anxiety, and stress-related disorders during the first year after cancer diagnosis.

Results

Among 316,904 patients identified, 5613 patients received a diagnosis of depression, anxiety, or stress-related disorders during the year after cancer diagnosis. Compared with no use of NSAIDs, the use of aspirin alone was associated with a lower rate of depression, anxiety, and stress-related disorders (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 to 0.97), whereas the use of non-aspirin NSAIDs alone was associated with a higher rate (HR, 1.24; 95% CI, 1.15 to 1.32), after adjustment for sociodemographic factors, comorbidity, indications for NSAID use, and cancer characteristics. The association of aspirin with reduced rate of depression, anxiety, and stress-related disorders was strongest for current use (HR, 0.84; 95% CI, 0.75 to 0.93), low-dose use (HR, 0.88; 95% CI, 0.80 to 0.98), long-term use (HR, 0.84; 95% CI, 0.76 to 0.94), and among patients with cardiovascular disease (HR, 0.81; 95% CI, 0.68 to 0.95) or breast cancer (HR, 0.74; 95% CI, 0.56 to 0.98).

Conclusion

Pre-diagnostic use of aspirin was associated with a decreased risk of depression, anxiety, and stress-related disorders during the first year following cancer diagnosis.
Treatment estimands in clinical trials of patients hospitalised for COVID-19: ensuring trials ask the right questions
Authors: Kahan Brennan C. , Morris Tim P. , White Ian R. , Tweed Conor D. , Cro Suzie , Dahly Darren , Pham Tra My , Esmail Hanif , Babiker Abdel , Carpenter James R.
Published: September 2020

When designing a clinical trial, explicitly defining the treatmentestimandsof interest (that which is to be estimated) can help to clarify trial objectives and ensure the questions being addressed by the trial are clinically meaningful. There are several challenges when defining estimands. Here, we discuss a number of these in the context of trials of treatments for patients hospitalised with COVID-19 and make suggestions for how estimands should be defined for key outcomes. We suggest that treatment effects should usually be measured as differences in proportions (or risk or odds ratios) for outcomes such as death and requirement for ventilation, and differences in means for outcomes such as the number of days ventilated. We further recommend that truncation due to death should be handled differently depending on whether a patient- or resource-focused perspective is taken; for the former, a composite approach should be used, while for the latter, a while-alive approach is preferred. Finally, we suggest that discontinuation of randomised treatment should be handled from a treatment policy perspective, where non-adherence is ignored in the analysis (i.e. intention to treat).
Re-emergence of porcine epidemic diarrhea virus in a piglet-producing farm in northwestern Germany in 2019
Authors: Karte Claudia , Platje Nadine , Bullermann Johannes , Beer Martin , Höper Dirk , Blome Sandra
Published: September 2020

Background

Porcine epidemic diarrhea (PED) is a viral enteric disease of pigs. It affects all age classes of animals but lethality is mainly seen in suckling piglets. After its first appearance in England in 1971, Porcine epidemic diarrhea virus (PEDV) has spread worldwide. While sporadic outbreaks prevailed in Europe, the disease had high impact in Asia. Following particularly severe outbreaks in 2011, high impact cases were also reported in the United States and neighboring countries in 2013. Subsequently, outbreaks were also reported in several European countries including Germany. These outbreaks were less severe. This case report describes a recent case of PED re-emergence in Germany and the sequence analyses of the causative PEDV.

Case presentation

In spring 2019 5 years after re-introduction of PED into Central Europe, a piglet-producer in northwestern Germany experienced an outbreak that affected sows, their suckling piglets, and weaners. After initial confirmation of PEDV by real-time RT-PCR, fecal material and small intestine samples from affected pigs were subjected to metagenomic analyses employing next-generation sequencing. Phylogenetic analyses showed high identities among the PEDV sequences obtained from samples of different animals and a close relation to recent strains from Hungary and France. Compared to the PEDV strains analyzed in 2014, genetic drift could be confirmed. Changes were mainly observed in the spike protein encoding S gene segment. In addition, metagenomic analyses showed multiple Picobirnavirus reads in all investigated samples.

Conclusion

This case report shows that PEDV is still circulating in Europe. The causative strains are moderately virulent and are still closely related to the so-called INDEL strains reported previously in Europe, including Germany. However, a genetic drift has taken place that can be seen in a novel cluster comprising strains from Germany, Hungary and France in 2019. Relevance and impact of the detected Picobirna sequences need further investigations.
Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator
Authors: Singh Dave , Balaguer Victor , Astbury Carol , Wählby-Hamrén Ulrika , Jimenez Eulalia , Seoane Beatriz , Villarroel Cristina , Lei Alejhandra , Aggarwal Ajay , Psallidas Ioannis
Published: September 2020

Background

Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist β2−agonist (MABA) molecule in development for the treatment of chronic obstructive pulmonary disease (COPD). The pharmacodynamics, safety and tolerability of single doses of navafenterol were investigated in patients with moderate to severe COPD.

Methods

This was a randomized, five-way complete cross-over study. Patients received single doses of navafenterol 400 μg, navafenterol 1800 μg and placebo (all double-blind) and indacaterol 150 μg and tiotropium 18 μg (both open-label active comparators). The primary pharmacodynamic endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) on day 2. Safety and tolerability were monitored throughout.

Results

Thirty-eight patients were randomized and 28 (73.7%) completed the study. Navafenterol 400 μg and 1800 μg demonstrated statistically significant improvements vs placebo in change from baseline in trough FEV1 (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P < .0001). The changes were significantly greater with navafenterol 1800 μg vs the active comparators (least squares mean treatment difference: 0.065–0.069 L, both P < .05). The frequency of treatment-emergent adverse events was similar for placebo and the active comparators (range 34.4–37.5%), slightly higher for navafenterol 400 μg (52.9%), and lowest for navafenterol 1800 μg (22.6%).

Conclusions

Both doses of navafenterol demonstrated sustained bronchodilation over 24 h. Navafenterol was well tolerated and no safety concerns were raised.

Trial registry

ClinicalTrials.gov; No.: NCT02573155; URL: www.clinicaltrials.gov. Registered 9th October, 2015.
Evaluation of the colorimetric malachite green loop-mediated isothermal amplification (MG-LAMP) assay for the detection of malaria species at two different health facilities in a malaria endemic area of western Kenya
Authors: Gachugia James , Chebore Winnie , Otieno Kephas , Ngugi Caroline Wangari , Godana Adano , Kariuki Simon
Published: September 2020

Background

Prompt diagnosis and effective malaria treatment is a key strategy in malaria control. However, the recommended diagnostic methods, microscopy and rapid diagnostic tests (RDTs), are not supported by robust quality assurance systems in endemic areas. This study compared the performance of routine RDTs and smear microscopy with a simple molecular-based colorimetric loop-mediated isothermal amplification (LAMP) at two different levels of the health care system in a malaria-endemic area of western Kenya.

Methods

Patients presenting with clinical symptoms of malaria at Rota Dispensary (level 2) and Siaya County Referral Hospital (level 4) were enrolled into the study after obtaining written informed consent. Capillary blood was collected to test for malaria by RDT and microscopy at the dispensary and county hospital, and for preparation of blood smears and dried blood spots (DBS) for expert microscopy and real-time polymerase chain reaction (RT-PCR). Results of the routine diagnostic tests were compared with those of malachite green loop-mediated isothermal amplification (MG-LAMP) performed at the two facilities.

Results

A total of 264 participants were enrolled into the study. At the dispensary level, the positivity rate by RDT, expert microscopy, MG-LAMP and RT-PCR was 37%, 30%, 44% and 42%, respectively, and 42%, 43%, 57% and 43% at the county hospital. Using RT-PCR as the reference test, the sensitivity of RDT and MG-LAMP was 78.1% (CI 67.5–86.4) and 82.9% (CI 73.0–90.3) at Rota dispensary. At Siaya hospital the sensitivity of routine microscopy and MG-LAMP was 83.3% (CI 65.3–94.4) and 93.3% (CI 77.9–99.2), respectively. Compared to MG-LAMP, there were 14 false positives and 29 false negatives by RDT at Rota dispensary and 3 false positives and 13 false negatives by routine microscopy at Siaya Hospital.

Conclusion

MG-LAMP is more sensitive than RDTs and microscopy in the detection of malaria parasites at public health facilities and might be a useful quality control tool in resource-limited settings.
Beyond clinical food prescriptions and mobile markets: parent views on the role of a healthcare institution in increasing healthy eating in food insecure families
Authors: DeWit Emily L. , Meissen-Sebelius Emily M. , Shook Robin P. , Pina Kimberly A. , De Miranda Evelyn Donis , Summar Michelle J. , Hurley Emily A.
Published: September 2020

Background

Children in food-insecure families face increased barriers to meeting recommendations for fruit and vegetable consumption. Hospitals and pediatric healthcare institutions have attempted to alleviate food-insecurity through various internal programs like food prescriptions, yet little evidence for these programs exist. Consistent with a patient-centered perspective, we sought to develop a comprehensive understanding of barriers to fruit and vegetable consumption and a parent-driven agenda for healthcare system action.

Methods

We conducted six qualitative focus group discussions (four in English, two in Spanish) with 29 parents and caregivers of patients who had screened positive for food-insecurity during visits to a large pediatric healthcare system in a midwestern U.S. city. Our iterative analysis process consisted of audio-recording, transcribing and coding discussions, aiming to produce a) a conceptual framework of barriers to fruit and vegetable consumption and b) a synthesis of participant programmatic suggestions for their healthcare system.

Results

Participants were 90% female, 38% Black/African American and 41% Hispanic/Latino. Barriers to fruit and vegetable consumption in their families fell into three intersecting themes: affordability, accessibility and desirability. Participant-generated intervention recommendations were multilevel, suggesting healthcare systems focus not only on clinic and community-based action, but also advocacy for broader policies that alleviate barriers to acquiring healthy foods.

Conclusion

Parents envision an expanded role for healthcare systems in ensuring their children benefit from a healthy diet. Findings offer critical insight on why clinic-driven programs aimed to address healthy eating may have failed and healthcare organizations may more effectively intervene by adopting a multilevel strategy.
Modern dietary pattern is prospectively associated with earlier age at menarche: data from the CHNS 1997–2015
Authors: Duan Ruonan , Chen Yue , Qiao Tian , Duan Ruotong , Chen Mengxue , Zhao Li , Gong Yunhui , Cheng Guo
Published: September 2020

Background

Early age at menarche is associated with risk of several chronic diseases. Prospective study on the association between dietary pattern and timing of menarche is sparse. We examined whether dietary patterns prior to the menarche onset were prospectively associated with menarcheal age in Chinese girls.

Methods

One thousand one hundred eighteen girls aged 6–13 y in the China Health and Nutrition Survey (CHNS) with three-day 24-h recalls and information on potential confounders at baseline were included in the study. Dietary patterns were identified using principal component analysis. Age at menarche was self-reported at each survey. Cox proportional hazard regression models were performed to examine the associations of premenarcheal dietary patterns and menarcheal timing. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Results

Three major dietary patterns were identified: modern dietary pattern, animal food pattern, and snack food pattern. After adjustment for age at baseline, region, ethnicity, maternal education level, energy intake at baseline, and body mass index Z-score at baseline, girls in the highest quartile of modern dietary pattern score had a 33% higher probability of experiencing menarche at an earlier age than those in the lowest quartile (HR: 1.33, 95% CI: 1.002–1.77, p for trend = 0.03). No significant association was found for the animal food pattern or snack food pattern.

Conclusions

Higher adherence to modern dietary pattern during childhood is associated with an earlier menarcheal age. This association was independent of premenarcheal body size.