bluuebunny/crossref_metadata_2025_split huggingface dataset:
Household and familial resemblance in risk factors for type 2 diabetes and related cardiometabolic diseases in rural Uganda: a cross-sectional community sample
Authors: Nielsen Jannie , Bahendeka Silver K , Whyte Susan R , Meyrowitsch Dan W , Bygbjerg Ib C , Witte Daniel R 
Published: September 2017

ObjectivesPrevention of type 2 diabetes (T2D) has been successfully established in randomised clinical trials. However, the best methods for the translation of this evidence into effective population-wide interventions remain unclear. To assess whether households could be a target for T2D prevention and screening, we investigated the resemblance of T2D risk factors at household level and by type of familial dyadic relationship in a rural Ugandan community.MethodsThis cross-sectional household-based study included 437 individuals ≥13 years of age from 90 rural households in south-western Uganda. Resemblance in glycosylated haemoglobin (HbA1c), anthropometry, blood pressure, fitness status and sitting time were analysed using a general mixed model with random effects (by household or dyad) to calculate household intraclass correlation coefficients (ICCs) and dyadic regression coefficients. Logistic regression with household as a random effect was used to calculate the ORs for individuals having a condition or risk factor if another household member had the same condition.ResultsThe strongest degree of household member resemblances in T2D risk factors was seen in relation to fitness status (ICC=0.24), HbA1c (ICC=0.18) and systolic blood pressure (ICC=0.11). Regarding dyadic resemblance, the highest standardised regression coefficient was seen in fitness status for spouses (0.54, 95% CI 0.32 to 0.76), parent–offspring (0.41, 95% CI 0.28 0.54) and siblings (0.41, 95% CI 0.25 to 0.57). Overall, parent–offspring and sibling pairs were the dyads with strongest resemblance, followed by spouses.ConclusionsThe marked degree of resemblance in T2D risk factors at household level and between spouses, parent–offspring and sibling dyads suggest that shared behavioural and environmental factors may influence risk factor levels among cohabiting individuals, which point to the potential of the household setting for screening and prevention of T2D.
Protocol for a realist review of complex interventions to prevent adolescents from engaging in multiple risk behaviours
Authors: Cooper Christina , Lhussier Monique , Shucksmith Janet , Carr Susan Mary 
Published: September 2017

ObjectivesAdolescent risk behaviours are a key health concern. The purpose of this research is to gaina deeper understanding of how, why, for whom, and inwhat circumstances complex adolescent risk behaviourprevention programmes are most successful.Methods and analysisTo understand how adolescent risk behaviour prevention programmes work in a reallife context, a realist synthesis will be undertaken, operationalised in four phases.Phase oneDeveloping a framework to map the theoretical and conceptual landscape of adolescent risk behaviour prevention. Guided by stakeholder consultation.Phase twoFormulating initial programme theories through exploration of the literature, along with primary data from professional stakeholder interviews.Phase threeRefining programme theories through more purposeful, in depth screening of the literature, along with primary qualitative data, from young people and professionals. Data will be collected through semi structured focus groups, to explore specific elements of the emerging programme theories.Phase fourTesting programme theories through interviews with youth workers, following consultation with young people, using vignettes to explore the relationship between specific programme theories. This relatively novel method of primary and secondary data integration within a realist synthesis will provide deeper insight in to young peoples lived experience of risk behaviour prevention programmes, while maintaining transparency in the process of programme theory development.Data analysisA realist logic of analysis will be used to align data from each phase with context mechanism outcome configurations or specific elements thereof. Substantive theory will then be sought to understand and explain the findings.Ethics and disseminationThis study has been approved by the Ethics committee at Northumbria University, UK. Findings will be disseminated through knowledge exchange with stakeholders, publications in peer-reviewed journals, conference presentations, and formal and informal reports.
Perceptions of parents and paediatricians on pain induced by bone marrow aspiration and lumbar puncture among children with acute leukaemia: a qualitative study in China
Authors: Wang Yu , Liu Qiang , Yu Jia-Ning , Wang Hai-Xia , Gao Lu-Lu , Dai Ya-Liang , Jin Xin , Zuo Feng , Liu Juan , Bai Cai-Feng , Mu Guo-Xia , Chai Xiao-Min , Zhang Yin-Juan , Li Yu-Xiang , Yu Jian-Qiang 
Published: September 2017

ObjectiveTo obtain in-depth insight into the perceptions of parents and paediatricians in China regarding current procedural pain management on bone marrow aspirations and lumbar punctures in paediatric haemato-oncology department.Design, setting and participantsThis qualitative study was conducted in a 4500-bed university hospital in northwest China. To collect data, in-depth semistructured interviews were conducted with parents of children with acute leukaemia (n=12) and haemato-oncology paediatricians (n=11) using purposive sampling. Interviews were audiotaped and transcribed and subjected to thematic analysis.ResultsThe suffering of procedural pain among paediatric patients was not adequately recognised and properly treated at the paediatric haemato-oncology department. The current paediatric procedural pain management is inadequate for paediatric patients. Crucial factors were identified including lack of awareness about the damage of uncontrolled pain in children, parents’ low supportive ability, the limited capacity to provide general analgesia by anaesthetists, inadequate knowledge in the usage of analgesia and sedation and lack of efficient analgesic for children’s procedural pain. The participants strongly expected optimal interventions to improve paediatric procedural pain management.ConclusionsThe result suggested a perceived and actual poor management of paediatric procedural pain in haemato-oncology department in northwest China. A relevant pain management education programme for paediatricians and parents as well as an effective pain medication are urgently needed in northwest China.Trial registrationChinese Clinical Trial Registry. Identifier: ChiCTR-INR-16007989.
Determinants of community pharmacists’ quality of care: a population-based cohort study using pharmacy administrative claims data
Authors: Winslade Nancy , Tamblyn Robyn 
Published: September 2017

ObjectiveTo determine if a prototype pharmacists’ services evaluation programme that uses linked community pharmacy claims and health administrative data to measure pharmacists’ performance can be used to identify characteristics of pharmacies providing higher quality of care.DesignPopulation-based cohort study using community pharmacy claims from 1 November 2009 to 30 June 2010.SettingAll community pharmacies in Quebec, Canada.Participants1742 pharmacies dispensing 8 655 348 antihypertensive prescriptions to 760 700 patients.Primary outcome measurePatient adherence to antihypertensive medications.PredictorsPharmacy level: dispensing workload, volume of pharmacist-provided professional services (eg, refusals to dispense, pharmacotherapy recommendations), pharmacy location, banner/chain, pharmacist overlap and within-pharmacy continuity of care. Patient level: sex, age, income, patient prescription cost, new/chronic therapy, single/multiple antihypertensive medications, single/multiple prescribers and single/multiple dispensing pharmacies. Dispensing level: prescription duration, time of day dispensed and antihypertensive class. Multivariate alternating logistic regression estimated predictors of the primary outcome, accounting for patient and pharmacy clustering.Results9.2% of dispensings of antihypertensive medications were provided to non-adherent patients. Male sex, decreasing age, new treatment, multiple prescribers and multiple dispensing pharmacies were risk factors for increased non-adherence. Pharmacies that provided more professional services were less likely to dispense to non-adherent hypertensive patients (OR: 0.60; 95% CI: 0.57 to 0.62) as were those with better scores on the Within-Pharmacy Continuity of Care Index. Neither increased pharmacists’ services for improving antihypertensive adherence per se nor increased pharmacist overlap impacted the odds of non-adherence. However, pharmacist overlap was strongly correlated with dispensing workload. There was significant unexplained variability among pharmacies belonging to different banners and chains.ConclusionsPharmacy administrative claims data can be used to calculate pharmacy-level characteristics associated with improved quality of care. This study supports the importance of pharmacist’s professional services and continuity of pharmacist’s care.
Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting
Authors: Argento Elena , Strathdee Steffanie A , Tupper Kenneth , Braschel Melissa , Wood Evan , Shannon Kate 
Published: September 2017

ObjectiveThis study aimed to longitudinally investigate whether ever having used a psychedelic drug can have a protective effect on incidence of suicidality among marginalised women.DesignLongitudinal community-based cohort study.SettingData were drawn from a prospective, community-based cohort of marginalised women in Metro Vancouver, Canada.Participants766 women completed the baseline questionnaire between January 2010 and August 2014. Participants who did not report suicidality at baseline and who completed at least one follow-up visit were included.Main outcome measureExtended Cox regression was used to model predictors of new suicidality (suicide ideation or attempts) over 54-month follow-up.ResultsNearly half (46%; n=355) of participants reported prior suicidality and were thus excluded from the present analyses. Of 290 women eligible at baseline, 11% (n=31) reported recent suicidality during follow-up, with an incidence density of 4.42 per 100 person-years (95% CI 3.10 to 6.30). In multivariable analysis, reported lifetime psychedelic drug use was associated with a 60% reduced hazard for suicidality (adjusted HR (AHR) 0.40; 95% CI 0.17 to 0.94). Crystal methamphetamine use (AHR 3.25; 95% CI 1.47 to 7.21) and childhood abuse (AHR 3.54; 95% CI 1.49 to 8.40) remained independent predictors of suicidality.ConclusionThe high rate of suicidality identified in this study is of major concern. Alongside emerging evidence on the potential of psychedelic-assisted therapy to treat some mental illness and addiction issues, our findings demonstrate that naturalistic psychedelic drug use is independently associated with reduced suicidality, while other illicit drug use and childhood trauma predispose women to suicidality. While observational, this study supports calls for further investigation of the therapeutic utility of psychedelic drugs in treating poor mental health and promoting mental wellness.
Help-seeking behaviours, opportunistic treatment and psychological implications of adolescent acne: cross-sectional studies in schools and hospital outpatient departments in the UK
Authors: Desai Karishma Parimal , Martyn-Simmons Claire , Viner Russell , Segal Terry 
Published: September 2017

BackgroundAcne vulgaris (acne) is a common adolescent skin condition. It is associated with negative psychological impacts and sufferers do not easily seek help, hence is undertreated.ObjectivesWe investigated the self-reported prevalence, severity and psychological sequelae of acne, together with assessing help-seeking behaviour and its barriers, in separate school and hospital samples. We explored opportunistic treatment by paediatricians.MethodsSelf-reported survey with participants drawn from: (1) 120 adolescents aged 13–18 in a London tertiary paediatric outpatient department and (2) 482 adolescents from two London schools, aged 11–18. Adolescents confidentially and anonymously completed a questionnaire (paper or online) and those with acne completed the Cardiff Acne Disability Index (CADI) questionnaire.Outcome measuresTo explore if acne is being addressed opportunistically in outpatient appointments and the behaviours associated with seeking help and psychological implications of acne.ResultsAcne prevalence was reported as 58.3% in the clinic and 42.3% in schools, with 34.3% and 20.6% of participants having moderate acne (MA) or severe acne (SA), respectively. The correlation between acne severity and CADI was significant (regression coefficient=4.86, p<0.005 (MA) and 9.08, p<0.005 (SA) in the hospital; 1.92, p<0.001 (MA) and 7.41, p<0.005 (SA) in schools). Severity of acne was associated with increased likelihood of seeing a doctor in both samples (OR=8.95, 2.79–28.70 (MA) in the clinic and 1.31, 1.30–2.90 (MA) and 3.89, 0.66–22.98 (SA) in the community). Barriers to help seeking included embarrassment and believing doctors were unapproachable. Doctors addressed acne opportunistically in 2.9% of the sample, although 16.7% of those with MA and SA wished their doctor had raised it.ConclusionAcne is common and has negative psychological implications, correlating with severity. Young people often forego seeking help and hospital clinicians rarely address acne opportunistically. Further work is needed to investigate how to reduce barriers to help seeking for acne.
Protocol of a randomised controlled trial characterising the immune responses induced by varicella-zoster virus (VZV) vaccination in healthy Kenyan women: setting the stage for a potential VZV-based HIV vaccine
Authors: Perciani Catia T , Jaoko Walter , Walmsley Sharon , Farah Bashir , Mahmud Salaheddin M , Ostrowski Mario , Anzala Omu , Team KAVI-ICR , MacDonald Kelly S 
Published: September 2017

IntroductionA protective HIV vaccine would be expected to induce durable effector immune responses at the mucosa, restricting HIV infection at its portal of entry. We hypothesise that use of varicella-zoster virus (VZV) as an HIV delivery vector could generate sustained and robust tissue-based immunity against HIV antigens to provide long-term protection against HIV. Given that HIV uniquely targets immune-activated T cells, the development of human vaccines against HIV must also involve a specific examination of the safety of the vector. Thus, we aim to evaluate the effects of VZV vaccination on the recipients’ immune activation state, and on VZV-specific circulating humoral and cellular responses in addition to those at the cervical and rectal mucosa.Methods and analysisThis open-label, randomised, longitudinal crossover study includes healthy Kenyan VZV-seropositive women at low risk for HIV infection. Participants receive a single dose of a commercial live-attenuated VZVOkavaccine at either week 0 (n=22) or at week 12 (n=22) of the study and are followed for 48 and 36 weeks postvaccination, respectively. The primary outcome is the change on cervical CD4+T-cell immune activation measured by the coexpression of CD38 and HLA-DR 12 weeks postvaccination compared with the baseline (prevaccination). Secondary analyses include postvaccination changes in VZV-specific mucosal and systemic humoral and cellular immune responses, changes in cytokine and chemokine measures, study acceptability and feasibility of mucosal sampling and a longitudinal assessment of the bacterial community composition of the mucosa.Ethics and disseminationThe study has ethical approval from Kenyatta National Hospital/University of Nairobi Ethics and Research Committee, the University of Toronto Research Ethics Board and by Kenyan Pharmacy and Poisons Board. Results will be presented at conferences, disseminated to participants and stakeholders as well as published in peer-reviewed journals.Trial registration numberNCT02514018. Pre-results.
Prognostic factors for specific lower extremity and spinal musculoskeletal injuries identified through medical screening and training load monitoring in professional football (soccer): a systematic review
Authors: Hughes Tom , Sergeant Jamie C , Parkes Matthew J , Callaghan Michael J 
Published: September 2017

BackgroundMedical screening and load monitoring procedures are commonly used in professional football to assess factors perceived to be associated with injury.ObjectivesTo identify prognostic factors (PFs) and models for lower extremity and spinal musculoskeletal injuries in professional/elite football players from medical screening and training load monitoring processes.MethodsThe MEDLINE, AMED, EMBASE, CINAHL Plus, SPORTDiscus and PubMed electronic bibliographic databases were searched (from inception to January 2017). Prospective and retrospective cohort studies of lower extremity and spinal musculoskeletal injury incidence in professional/elite football players aged between 16 and 40 years were included. The Quality in Prognostic Studies appraisal tool and the modified Grading of Recommendations Assessment, Development and Evaluation synthesis approach was used to assess the quality of the evidence.ResultsFourteen studies were included. 16 specific lower extremity injury outcomes were identified. No spinal injury outcomes were identified. Meta-analysis was not possible due to heterogeneity and study quality. All evidence related to PFs and specific lower extremity injury outcomes was of very low to low quality. On the few occasions where multiple studies could be used to compare PFs and outcomes, only two factors demonstrated consensus. A history of previous hamstring injuries (HSI) and increasing age may be prognostic for future HSI in male players.ConclusionsThe assumed ability of medical screening tests to predict specific musculoskeletal injuries is not supported by the current evidence. Screening procedures should currently be considered as benchmarks of function or performance only. The prognostic value of load monitoring modalities is unknown.
Hepatoma-intrinsic CCRK inhibition diminishes myeloid-derived suppressor cell immunosuppression and enhances immune-checkpoint blockade efficacy
Authors: Zhou Jingying , Liu Man , Sun Hanyong , Feng Yu , Xu Liangliang , Chan Anthony W H , Tong Joanna H , Wong John , Chong Charing Ching Ning , Lai Paul B S , Wang Hector Kwong-Sang , Tsang Shun-Wa , Goodwin Tyler , Liu Rihe , Huang Leaf , Chen Zhiwei , Sung Joseph JY , Chow King Lau , To Ka Fai , Cheng Alfred Sze-Lok 
Published: September 2017

ObjectiveMyeloid-derived suppressor cells (MDSCs) contribute to tumour immunosuppressive microenvironment and immune-checkpoint blockade resistance. Emerging evidence highlights the pivotal functions of cyclin-dependent kinases (CDKs) in tumour immunity. Here we elucidated the role of tumour-intrinsic CDK20, or cell cycle-related kinase (CCRK) on immunosuppression in hepatocellular carcinoma (HCC).DesignImmunosuppression of MDSCs derived from patients with HCC and relationship with CCRK were determined by flow cytometry, expression analyses and co-culture systems. Mechanistic studies were also conducted in liver-specific CCRK-inducible transgenic (TG) mice and Hepa1–6 orthotopic HCC models using CRISPR/Cas9-mediated Ccrk depletion and liver-targeted nanoparticles for interleukin (IL) 6 trapping. Tumorigenicity and immunophenotype were assessed on single or combined antiprogrammed death-1-ligand 1 (PD-L1) therapy.ResultsTumour-infiltrating CD11b+CD33+HLA-DR− MDSCs from patients with HCC potently inhibited autologous CD8+T cell proliferation. Concordant overexpression of CCRK and MDSC markers (CD11b/CD33) positively correlated with poorer survival rates. Hepatocellular CCRK stimulated immunosuppressive CD11b+CD33+HLA-DR− MDSC expansion from human peripheral blood mononuclear cells through upregulating IL-6. Mechanistically, CCRK activated nuclear factor-κB (NF-κB) via enhancer of zeste homolog 2 (EZH2) and facilitated NF-κB-EZH2 co-binding to IL-6 promoter. Hepatic CCRK induction in TG mice activated the EZH2/NF-κB/IL-6 cascade, leading to accumulation of polymorphonuclear (PMN) MDSCs with potent T cell suppressive activity. In contrast, inhibiting tumorous Ccrk or hepatic IL-6 increased interferon γ+tumour necrosis factor-α+CD8+ T cell infiltration and impaired tumorigenicity, which was rescued by restoring PMN-MDSCs. Notably, tumorous Ccrk depletion upregulated PD-L1 expression and increased intratumorous CD8+ T cells, thus enhancing PD-L1 blockade efficacy to eradicate HCC.ConclusionOur results delineate an immunosuppressive mechanism of the hepatoma-intrinsic CCRK signalling and highlight an overexpressed kinase target whose inhibition might empower HCC immunotherapy.
Effects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial
Authors: Furie Karen L , Viscoli Catherine M , Gorman Mark , Ford Gary A , Young Lawrence H , Inzucchi Silvio E , Guarino Peter D , Lovejoy Anne M , Conwit Robin , Tanne David , Kernan Walter N 
Published: September 2017

IntroductionPatients with cerebrovascular disease are at increased risk for cognitive dysfunction. Modification of vascular risk factors, including insulin resistance, could improve poststroke cognitive function.MethodsIn the Insulin Resistance Intervention after Stroke (IRIS) trial, patients with a recent ischaemic stroke or transient ischaemic attack (TIA) were randomised to pioglitazone (target 45 mg daily) or placebo. All patients were insulin resistant based on a Homeostasis Model Assessment-Insulin Resistance score >3.0. For this preplanned analysis of cognitive function, we examined the Modified Mini-Mental State Examination (3MS) score (maximum score, 100) during follow-up. Patients were tested at baseline and annually for up to 5 years. Longitudinal mixed model methods were used to compare changes in the 3MS over time.ResultsOf the 3876 IRIS participants, 3398 had a 3MS score at baseline and at least once during follow-up and were included in the analysis. Median 3MS score at baseline was 97 (IQR 93–99). The average overall least squared mean 3MS score increased by 0.27 in the pioglitazone group and by 0.29 in the placebo group (mean difference between treatment groups −0.02; 95% CI −0.33 to 0.28, p=0.88).ConclusionsAmong insulin-resistant patients with a recent ischaemic stroke or TIA, pioglitazone did not affect cognitive function, as measured by the 3MS, over 5 years.Trial registrationClinicalTrials.gov NCT00091949; Results.
Evidence that iron accelerates Alzheimer’s pathology: a CSF biomarker study
Authors: Ayton Scott , Diouf Ibrahima , Bush Ashley Ian 
Published: September 2017

ObjectiveTo investigate whether cerebrospinal fluid (CSF) ferritin (reporting brain iron) is associated with longitudinal changes in CSF β-amyloid (Aβ) and tau.MethodsMixed-effects models of CSF Aβ1-42 and tau were constructed using data from 296 participants who had baseline measurement of CSF ferritin and annual measurement of CSF tau and Aβ1-42 for up to 5 years.ResultsIn subjects with biomarker-confirmed Alzheimer’s pathology, high CSF ferritin (>6.2 ng/mL) was associated with accelerated depreciation of CSF Aβ1-42 (reporting increased plaque formation; p=0.0001). CSF ferritin was neither associated with changes in CSF tau in the same subjects, nor longitudinal changes in CSF tau or Aβ1-42 in subjects with low baseline pathology. In simulation modelling of the natural history of Aβ deposition, which we estimated to occur over 31.4 years, we predicted that it would take 12.6 years to reach the pathology threshold value of CSF Aβ from healthy normal levels, and this interval is not affected by CSF ferritin. CSF ferritin influences the fall in CSF Aβ over the next phase, where high CSF ferritin accelerated the transition from threshold preclinical Aβ levels to the average level of Alzheimer’s subjects from 18.8 to 10.8 years.ConclusionsIron might facilitate Aβ deposition in Alzheimer’s and accelerate the disease process.