bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of ceftriaxone in paediatrics: a systematic review
Authors: Zeng Linan , Wang Chao , Jiang Min , Chen Kexin , Zhong Haiqin , Chen Zhe , Huang Liang , Li Hailong , Zhang Lingli , Choonara Imti 
Published: September 2020

ObjectiveTo determine the safety of ceftriaxone in paediatric patients and systematically evaluate the categories and incidences of adverse drug reactions (ADRs) of ceftriaxone in paediatric patients.MethodsWe performed a systematic search in Medline, PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, International Pharmaceutical Abstracts and bibliographies of relevant articles up to December 2018 for all types of studies that assessed the safety of ceftriaxone in paediatric patients aged ≤18 years.Results112 studies met the inclusion criteria involving 5717 paediatric patients who received ceftriaxone and reported 1136 ADRs. The most frequent ADRs reported in prospective studies were gastrointestinal (GI) disorders (37.4 %, 292/780), followed by hepatobiliary disorders (24.6%, 192/780). Serious ADRs leading to withdrawal or discontinuation of ceftriaxone were reported in 86 paediatric patients. Immune haemolytic anaemia (34.9%, 30/86) and biliary pseudolithiasis (26.7%, 23/86) were the two major causes. Haemolytic anaemia following intravenous ceftriaxone led to death in 11 children whose primary disease was sickle cell disease. Almost all biliary pseudolithiasis are reversible. However, the incidence was high affecting one in five paediatric patients (20.7%).ConclusionsGI ADRs are the most common toxicity of ceftriaxone in paediatric patients. Immune haemolytic anaemia and biliary pseudolithiasis are the most serious ADRs and the major reasons for discontinuation of ceftriaxone. Immune haemolytic anaemia is more likely in children with sickle cell disease and may cause death. Ceftriaxone should be used with caution in children with sickle cell disease.Trial registration numberCRD42017055428
Examining patient distress and unmet need for support across UK renal units with varying models of psychosocial care delivery: a cross-sectional survey study
Authors: Seekles Maaike , Ormandy Paula , Kamerāde Daiga 
Published: September 2020

ObjectiveTo examine in-centre haemodialysis patients’ emotional distress and need for support across UK renal units with varying models of psychosocial service provision.DesignThe study used a cross-sectional survey design. Logistic regression analysis was used to examine patient distress, as captured by the Distress Thermometer, and need for support, across different renal units.SettingSeven renal units across England, Wales and Scotland. The units were purposively selected so that varying workforce models of renal psychosocial services were represented.ParticipantsIn total, 752 patients were on dialysis in the participating centres on the days of data collection. All adult patients, who could understand English, and with capacity (as determined by the nurse in charge), were eligible to participate in the study. The questionnaire was completed by 509 patients, resulting in an overall response rate of 67.7%.Outcome measuresThe prevalence of distress and patient-reported need for support.ResultsThe results showed that 48.9% (95% CI 44.5 to 53.4) of respondents experienced distress. A significant association between distress and models of renal psychosocial service provision was found (χ2(6)=15.05, p=0.019). Multivariable logistic regression showed that patients in units with higher total psychosocial staffing ratios (OR 0.65 (95% CI 0.47 to 0.89); p=0.008) and specifically higher social work ratios (OR 0.49 (95% CI 0.33 to 0.74); p=0.001) were less likely to experience distress, even after controlling for demographic variables. In addition, a higher patient-reported unmet need for support was found in units where psychosocial staffing numbers are low or non-existent (χ2(6)=37.80, p<0.001).ConclusionsThe novel findings emphasise a need for increased incorporation of dedicated renal psychosocial staff into the renal care pathway. Importantly, these members of staff should be able to offer support for psychological as well as practical and social care-related issues.
Association of age-related macular degeneration on fracture risks among osteoporosis population: a nationwide population-based cohort study
Authors: Sun Chi Chin , Huang Ting-Shuo , Fu Tsai-Sheng , Lee Chia-Yi , Chen Bing-Yu , Chen Fang-Ping 
Published: September 2020

ObjectivesVisual impairment is an important risk factor for fracture in the elderly population. Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment in elderly people. This study was conducted to explore the relationship between AMD and incident fractures in patients with osteoporosis (OS).DesignRetrospective analysis of Taiwan’s National Health Insurance Research Database (NHIRD).SettingA multicenter study conducted in Taiwan.Participants and controlsThe current study used the NHIRD in Taiwan between 1996 and 2011. A total of 13 584 and 54 336 patients with OS were enrolled in the AMD group and the non-AMD group, respectively.InterventionPatients with OS were included from the Taiwan’s NHIRD after exclusion, and each patient with AMD was matched for age, sex and comorbidities to four patients with non-AMD OS, who served as the control group. A Cox proportional hazard model was used for the multivariable analysis.Primary outcome measuresTransitions for OS to spine fracture, OS to hip fracture, OS to humero-radio-ulnar fracture and OS to death.ResultsThe risks of spine and hip fractures were significantly higher in the AMD group (HR=1.09, 95% CI=1.04 to 1.15, p<0.001; HR=1.18; 95% CI=1.08 to 1.30, p=0.001, respectively) than in the non-AMD group. The incidence of humero-radio-ulnar fracture between AMD and non-AMD individuals was similar (HR=0.98; 95% CI=0.90 to 1.06; p=0.599). However, the risk of death was higher in patients with OS with older age, male sex and all types of comorbidity (p<0.05), except for hyperthyroidism (p=0.200).ConclusionPatients with OS with AMD had a greater risk of spine and hip fractures than did patients without AMD.
Association between guidelines and medical practitioners’ perception of best management for patients attending with an apparently uncomplicated acute sore throat: a cross-sectional survey in five countries
Authors: Gunnarsson Ronny , Ebell Mark H , Wächtler Hannelore , Manchal Naveen , Reid Lynne , Malmberg Stefan , Hawkey Sean , Hay Alastair D , Hedin Katarina , Sundvall Pär-Daniel 
Published: September 2020

ObjectiveTo investigate the relationship between guidelines and the medical practitioners’ perception of optimal care for patients attending with an apparently uncomplicated acute sore throat in five countries (Australia, Germany, Sweden, UK and USA).DesignInternational cross-sectional survey.SettingPrimary healthcare (PHC).ParticipantsMedical practitioners working in PHC.Main outcome measuresORs for: (A) perception of throat swabs as important, (B) perception of blood tests (C reactive protein, B-ESR and B-leucocytes) as important and (C) antibiotic prescriptions if no pathogenic bacteria isolated on throat swab.ResultsGuidelines differed significantly; those recommending throat swabs (Sweden and USA) were associated with practitioners perceiving them as important. The UK guideline was the only one actively discouraging the use of throat swabs. Hence, compared with the USA (reference), a throat swab showing no pathogenic bacteria increased the probability of antibiotic prescribing in the UK with OR 3.2 (95% CI 1.7 to 6.1) for adults, whereas it reduced the probability in Sweden for adults OR 0.35 (95% CI 0.13 to 0.96) and children 0.19 (95% CI 0.069 to 0.50).ConclusionsThe differences between practitioners’ perceptions of best management were associated with their guidelines. It remains unclear if guidelines influenced medical practitioners’ perception or if guidelines merely reflect the consensus of current practice. A larger effort should be made to reach an international consensus in high-income countries about the best management of patients attending for an uncomplicated acute sore throat.
Women and partners’ experiences of critical perinatal events: a qualitative study
Authors: Navne Laura Emdal , Høgh Stinne , Johansen Marianne , Svendsen Mette Nordahl , Sorensen Jette Led 
Published: September 2020

ObjectiveThe aim of this study was to explore women and partners’ experiences following critical perinatal events.DesignThis is a qualitative interview study. We conducted semistructured individual interviews with women and their partners in separate rooms. Interviews were analysed thematically and validated by a transdisciplinary group of anthropologists, obstetricians and a midwife.SettingDepartment of obstetrics at a tertiary referral university hospital in Denmark.ParticipantsWomen and partners who had experienced a critical perinatal event within the past 3–12 months.ResultsWe conducted 17 interviews and identified three main themes: (1) ambivalence towards medicalisation, (2) the extended temporality of a critical birth and (3) postnatal loss of attention from healthcare professionals. Overall, participants expressed a high degree of trust in and quality of provided healthcare during the critical perinatal events. They experienced medicalisation (obstetric interventions) as a necessity, linking them to the safety of the child and their new role as responsible parents. However, some women experienced disempowerment when healthcare professionals overlooked their ability to stay actively involved during birth events. Postnatally, women and their partners experienced shortages of healthcare professional resources, absent healthcare and lack of attention.ConclusionsWomen and their partners’ experiences of critical perinatal events begin long before and end long after the actual moment of childbirth, challenging conventional ideas about the birth as being the pivotal event in making families. In future healthcare planning, it is important to to align expectations and guide parental involvement in birth events and to acknowledge the postnatal period as equally crucial.
Comprehensive Cervical Cancer Prevention in Tanzania (CONCEPT) study: Cohort profile
Authors: Mchome Bariki , Swai Patricia , Wu Chunsen , Katanga Johnson , Kahesa Crispin , Manongi Rachel , Mwaiselage Julius D , Kjaer Susanne , Rasch Vibeke , Linde Ditte Søndergaard 
Published: September 2020

PurposeCervical cancer is a major cause of death among women in Eastern Africa, and the distribution of human papillomavirus (HPV) according to HIV status is inadequately characterised in this region. In order to guide future cervical cancer preventive strategies that involve HPV testing, the Comprehensive Cervical Cancer Prevention in Tanzania (CONCEPT) study was established in 2015. The CONCEPT cohort aims to investigate the natural history of HPV and determine acquisition and persistence patterns of high-risk (HR) HPV among HIV-positive and HIV-negative women. Further, the influence of lifestyle and sexual/reproductive factors will be investigated. The main objective of this article is to describe how the CONCEPT cohort was established.ParticipantsWomen aged 25–60 years were enrolled from cervical cancer screening clinics in Dar-es-Salaam and Moshi, Tanzania. Data were collected at baseline, at 14 months (first follow-up) and at 28 months (second follow-up). Biological samples included two cervical swabs for careHPV DNA testing, cytology, Hybrid Capture 2, genotyping and blood samples for HIV. Visual inspection with acetic acid was performed, and sociodemographic, lifestyle and sexual/reproductive characteristics were collected through a standardised questionnaire.Findings to date4043 women were included in the cohort from August 2015 to May 2017. At baseline, 696 (17.1%) women were HR HPV positive, and among these, 31.6% were HIV positive; 139 women (3.4%) had high-grade squamous intraepithelial lesions. 3074 women (81%) attended the first follow-up. The majority attended after receiving a phone call reminder (35%) or from home via self-samples (41%). At first follow-up, 438 (14.4%) were HR HPV positive and 30.4% of these were HIV positive.Future plansA second follow-up is underway (17 December 2018–October 2020). We plan to integrate our data with a previous cross-sectional HPV study from Tanzania to increase the power of our findings. Researchers interested in collaborating are welcomed, either by extracting data or jointly requesting further investigation from the cohort.
Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort
Authors: Levy Sonja , Aarts Maureen J B , Eskens Ferry A L M , Keymeulen Kristien B M I , Been Lukas B , Grünhagen Dirk , van Akkooi Alexander , Jalving Mathilde , Tesselaar Margot E T 
Published: September 2020

BackgroundMerkel cell carcinoma (MCC) is associated with high recurrence rates and poor survival when metastatic disease is present. The immune checkpoint inhibitor avelumab has shown high response rates (RRs) and durable responses in patients with advanced MCC (aMCC) in clinical trials. To date, only results from clinical trials, patients treated in an expanded access program and very small numbers of patients have been reported. In this study, detailed real-world efficacy and toxicity data of avelumab in patients with aMCC are reported.MethodsPatients with aMCC treated in four dedicated referral centers in the Netherlands were analyzed from February 2017 until December 2019. Patients were included if they had received at least one administration of avelumab, regardless of previous lines of therapy. Patient data were collected retrospectively from patient records. Primary endpoints were response rate (RR) and duration of response (DOR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity.ResultsFifty-four patients received avelumab. Eight (15%) patients had locally advanced disease (laMCC). In 40 (74%) patients, avelumab was first-line treatment, these included all patients with laMCC. The median follow-up was 8.9 (range 0.5–35.9) months. RR was 57% (n=31) with 24% (n=13) of patients achieving a complete response. The median DOR was 8.4 (range 1.3–22.1) months and 23 (43%) patients had an ongoing response at the end of the study. The median PFS was 8.6 (95% CI 1.6–15.5) months, and the median OS was 25.8 (95% CI 9.1–42.4) months. Six (11%) patients experienced grade 3 toxicity. No grade 4–5 toxicity was seen.ConclusionsIn this real-world cohort, clinical efficacy and toxicity outcomes in clinical practice were in line with results from clinical trials and showed relatively high RRs and durable responses in patients with aMCC.
Tales of treatment and new perspectives for global health research on antimicrobial resistance
Authors: Haenssgen Marco J , Charoenboon Nutcha , Thavethanutthanawin Patthanan , Wibunjak Kanokporn 
Published: September 2020

Global health champions modernism and biomedical knowledge but tends to neglect knowledge, beliefs and identities of rural communities in low-income and middle-income countries. The topic of antimicrobial resistance represents these common challenges, wherein the growing emphasis on public engagement offers a yet underdeveloped opportunity to generate perspectives and forms of knowledge that are not typically incorporated into research and policy. The medical humanities as an interdisciplinary approach to illness and health behaviour play a central role in cultivating this potential—in particular, through the field’s emphasis on phenomenological and intersubjective approaches to knowledge generation and its interest in dialogue between medicine, the humanities and the broader public.We present a case study of public engagement that incorporates three medical humanities methods: participatory co-production, photographic storytelling and dialogue between researchers and the public. Situated in the context of northern Thailand, we explore subcases on co-production workshops with villagers, tales of treatment shared by traditional healers and dialogue surrounding artistic display in an international photo exhibition. Our starting assumption for the case study analysis was that co-produced local inputs can (and should) broaden the understanding of the sociocultural context of antimicrobial resistance.Our case study illustrates the potential of medical humanities methods in public engagement to foreground cultural knowledge, personal experience and ‘lay’ sensemaking surrounding health systems and healing (including medicine use). Among others, the engagement activities enabled us to formulate and test locally grounded hypotheses, gain new insights into the social configuration of treatment seeking and reflect on the relationship between traditional healing and modern medicine in the context of antimicrobial resistance. We conclude that medical-humanities-informed forms of public engagement should become a standard component of global health research, but they require extensive evaluation to assess benefits and risks comprehensively.
Digestibility of amino acids in pigs fed distillers dried grains with solubles derived from corn, sorghum, and triticale
Authors: Park Chan Sol , Ragland Darryl , Adeola Olayiwola 
Published: September 2020

An experiment was conducted to determine the standardized ileal digestibility (SID) of amino acids (AA) in distillers dried grains with solubles derived from corn (C-DDGS), sorghum (S-DDGS), and triticale (T-DDGS) fed to growing pigs. A total of 16 barrows [initial body weight (BW) = 23.1 ± 2.03 kg] surgically fitted with T-cannulas at the distal ileum were divided into four groups based on BW and assigned to a quadruplicated 4 × 2 incomplete Latin square design with four dietary treatments and two experimental periods. Three diets containing C-DDGS, S-DDGS, or T-DDGS, as well as a nitrogen-free diet, were fed in each experimental period consisting of 5 d of adaptation and 2 d of ileal digesta collection. Pigs fed S-DDGS had less (P < 0.05) SID of histidine, isoleucine, leucine, and methionine compared with those fed T-DDGS, which were less (P < 0.05) than the values observed for pigs fed C-DDGS. The SID of arginine, phenylalanine, threonine, and valine in C-DDGS were greater (P < 0.05) than in S-DDGS but were not different from those in T-DDGS. The SID of lysine in C-DDGS was greater (P < 0.05) than in S-DDGS and T-DDGS. In conclusion, AA in S-DDGS were less digestible than those in C-DDGS and T-DDGS.
On the co-movement of crude, gold prices and stock index in the Indian market
Authors: Sen Abhibasu , Choudhury Karabi Dutta 
Published: September 2020

The nonlinear relationship in the joint time-frequency domain has been studied for the Indian National Stock Exchange (NSE) with the international Gold price and WTI Crude Price being converted from Dollar to Indian National Rupee based on that week’s closing exchange rate. Though a good correlation was obtained during some period, but as a whole no such cointegration relation can be found out. Using the Discrete Wavelet Analysis, the data was decomposed and the presence of Granger Causal relations was tested. Unfortunately, no significant relationships are being found. We then studied the Wavelet Coherence of the two pairs, namely NSE-Nifty & Gold and NSE-Nifty & Crude. For different frequencies, the coherence between the pairs have been studied. At lower frequencies, some relatively good coherence have been found. In this paper, we report for the first time the co-movements between Crude Oil, Gold and Indian Stock Market Index using Wavelet Analysis (both Discrete and Continuous), a technique which is most sophisticated and recent in market analysis. Thus, for long-term traders they can include gold and/or crude in their portfolio along with NSE-Nifty index in order to decrease the risk (volatility) of the portfolio for the Indian Market. But for short-term traders, it will not be effective, not to include all the three in their portfolio.
Enhanced Immunotherapy with LHRH-R Targeted Lytic Peptide in Ovarian Cancer
Authors: Kim Mark Seungwook , Ma Shaolin , Chelariu-Raicu Anca , Leuschner Carola , Alila Hector W. , Lee Sanghoon , Coleman Robert L. , Sood Anil K. 
Published: September 2020

AbstractHere, we examined the role of EP-100 [luteinizing hormone-releasing hormone (LHRH) ligand joined to a lytic peptide], improving the efficacy of immune checkpoint blockade. LHRH-R–positive murine ovarian cancer cells (ID8, IG10, IF5, and 2C12) were sensitive to EP-100 and were specifically killed at low micromolar levels through LHRH-R. EP-100 increased PD-L1 levels on murine ovarian cancer cells. In vivo syngeneic mouse models (ID8 and IG10) demonstrated that single-agent EP-100 reduced tumor volume, tumor weight, and ascites volume. The greatest reductions in tumor and ascites volume were observed with the combination of EP-100 with an anti–PD-L1 antibody. Immune profiling analysis showed that the population of CD8+ T cells, natural killer cells, dendritic cells, and macrophages were significantly increased in tumor and ascitic fluid samples treated with anti–PD-L1, EP-100, and the combination. However, monocytic myeloid suppressor cells, B cells, and regulatory T cells were decreased in tumors treated with anti–PD-L1, EP-100, or the combination. In vitro cytokine arrays revealed that EP-100 induced IL1α, IL33, CCL20, VEGF, and Low-density lipoprotein receptor (LDLR) secretion. Of these, we validated increasing IL33 levels following EP-100 treatment in vitro and in vivo; we determined the specific biological role of CD8+ T-cell activation with IL33 gene silencing using siRNA and Cas9-CRISPR approaches. In addition, we found that CD8+ T cells expressed very low level of LHRH-R and were not affected by EP-100. Taken together, EP-100 treatment had a substantial antitumor efficacy, particularly in combination with an anti–PD-L1 antibody. These results warrant further clinical development of this combination.
CH7233163 Overcomes Osimertinib-Resistant EGFR-Del19/T790M/C797S Mutation
Authors: Kashima Kenji , Kawauchi Hiroki , Tanimura Hiromi , Tachibana Yukako , Chiba Takashi , Torizawa Takuya , Sakamoto Hiroshi 
Published: September 2020

Abstract
Osimertinib is the only EGFR-tyrosine kinase inhibitor (TKI) capable of overcoming EGFR-T790M–mutated NSCLC, but osimertinib-resistant EGFR triple mutations (Del19/T790M/C797S or L858R/T790M/C797S) have been reported. Although allosteric EGFR TKIs (e.g., EAI-045) that potentially overcome L858R/T790M/C797S have been identified, there are no effective inhibitors against Del19/T790M/C797S. In this study, we identified CH7233163 as having the potential to overcome EGFR-Del19/T790M/C797S. CH7233163 showed potent antitumor activities against tumor with EGFR-Del19/T790M/C797S in vitro and in vivo. In addition to EGFR-Del19/T790M/C797S, the characterization assays showed that CH7233163 more selectively inhibits various types of EGFR mutants (e.g., L858R/T790M/C797S, L858R/T790M, Del19/T790M, Del19, and L858R) over wild type. Furthermore, crystal structure analysis suggested that CH7233163 is a noncovalent ATP-competitive inhibitor for EGFR-Del19/T790M/C797S that utilizes multiple interactions with the EGFR's αC-helix-in conformation to achieve potent inhibitory activity and mutant selectivity. Therefore, we conclude that CH7233163 is a potentially effective therapy for osimertinib-resistant patients, especially in cases of EGFR-Del19/T790M/C797S.