bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between leukocytospermia and semen interleukin‐6 and tumor necrosis factor‐alpha in infertile men
Authors: Eldamnhoury E. M. , Elatrash G. A. , Rashwan H. M. , El‐Sakka A. I.
Published: July 2018

Seminal cytokines were previously reported to adversely affect process of spermatogenesis and ultimately induce poor semen quality. However, association between both IL‐6 and TNF‐α and leukocytospermia was not yet settled. The aim of this study was to evaluate the association between leukocytospermia and levels of interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α) in semen of infertile men. This cross‐sectional study included 100 age‐matched (≥18–45 years.) men. Participants were divided into four groups with 25 patients in each group: Group (A) – infertile patients with leukocytospermia and normal other semen parameters; Group (B) – infertile patients with leukocytospermia and abnormal semen parameters; Group (C) – infertile patients with oligospermia and/or asthenospermia and/or teratospermia but with no leukocytospermia; Group (D) – fertile patients with normal semen parameters and without leukocytospermia. All patients were assessed by detailed medical, sexual, fertility history, and complete physical examination. Laboratory assessment included hormonal and semen analysis and assessment of IL‐6 and TNF‐α in semen plasma. There were significant differences among the study groups regarding total sperm count, sperm concentration, and progressive motility (p < 0.05 for each). There was significant increase in semen WBC counts in groups A and B vs. groups C and D (p = 0.003). There were significant associations between increase levels of WBCs ≥ 5/HPF and decrease levels of total sperm count (p = 0.023), sperm concentration (p = 0.001), and sperm progressive motility (p = 0.02). There were significant upregulations in mean level of IL‐6 (p = 0.001) and mean level of TNF‐α (p = 0.003) in groups A and B vs. groups C and D. Overall, leukocytospermia is associated with reduction in sperm count, progressive motility and further upregulation of seminal IL‐6 and TNF‐α. The effect of treatment of leukocytospermia on the level of seminal cytokines is important point of future research.
Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol‐dimethylheptyl at the type 1 and type 2 cannabinoid receptors
Authors: Tham Mylyne , Yilmaz Orhan , Alaverdashvili Mariam , Kelly Melanie E M , Denovan‐Wright Eileen M , Laprairie Robert B
Published: July 2018

Background and Purpose

We sought to understand why (−)‐cannabidiol (CBD) and (−)‐cannabidiol‐dimethylheptyl (CBD‐DMH) exhibit distinct pharmacology, despite near identical structures.

Experimental Approach

HEK293A cells expressing either human type 1 cannabinoid (CB1) receptors or CB2 receptors were treated with CBD or CBD‐DMH with or without the CB1 and CB2 receptor agonist CP55,940, CB1 receptor allosteric modulator Org27569 or CB2 receptor inverse agonist SR144528. Ligand binding, cAMP levels and βarrestin1 recruitment were measured. CBD and CBD‐DMH binding was simulated with models of human CB1 or CB2 receptors, based on the recently published crystal structures of agonist‐bound (5XRA) or antagonist‐bound (5TGZ) human CB1 receptors.

Key Results

At CB1 receptors, CBD was a negative allosteric modulator (NAM), and CBD‐DMH was a mixed agonist/positive allosteric modulator. CBD and Org27569 shared multiple interacting residues in the antagonist‐bound model of CB1 receptors (5TGZ) but shared a binding site with CP55,940 in the agonist‐bound model of CB1 receptors (5XRA). The binding site for CBD‐DMH in the CB1 receptor models overlapped with CP55,940 and Org27569. At CB2 receptors, CBD was a partial agonist, and CBD‐DMH was a positive allosteric modulator of cAMP modulation but a NAM of βarrestin1 recruitment. CBD, CP55,940 and SR144528 shared a binding site in the CB2 receptor models that was separate from CBD‐DMH.

Conclusion and Implications

The pharmacological activity of CBD and CBD‐DMH in HEK293A cells and their modelled binding sites at CB1 and CB2 receptors may explain their in vivo effects and illuminates the difficulties associated with the development of allosteric modulators for CB1 and CB2 receptors.

Linked Articles

This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
Branched rolling circle amplification method for measuring serum circulating microRNA levels for early breast cancer detection
Authors: Fan Tingting , Mao Yu , Sun Qinsheng , Liu Feng , Lin Jin‐Shun , Liu Yajie , Cui Junwei , Jiang Yuyang
Published: July 2018

Serum circulating microRNAs (c‐miRNAs) are serving as useful biomarkers for cancer diagnosis. Here, we describe the development of a one‐step branched rolling circle amplification (BRCA) method to measure serum c‐miRNAs levels for early diagnosis of breast cancer. Four c‐miRNAs, c‐miRNA16 (c‐miR‐16), c‐miRNA21 (c‐miR‐21), c‐miRNA155 (c‐miR‐155), and c‐miRNA195 (c‐miR‐195) were isolated from the serum of 49 breast cancer patients (stages I‐IV) and 19 healthy controls, and analyzed using one‐step BRCA. The serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 were higher (P < 0.0001) in stage I breast cancer patients than healthy controls. These levels were also higher in several breast cancer molecular subtypes (HER‐2 over‐expression, Luminal A, Luminal B, and triple negative breast cancer) than in healthy control subjects. The diagnostic accuracy of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 for early diagnosis of breast cancer was confirmed by receiver operating characteristic (ROC) curve assay. These results show that the BRCA method can be used to measure serum c‐miRNAs levels, and that this method has high accuracy, sensitivity, and specificity. Moreover, both BRCA approach and quantitative real‐time PCR (qRT‐PCR) method show that the serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 could be used as biomarkers to improve the early diagnosis of breast cancer, and distinguish different breast cancer molecular subtypes.
Canakinumab treatment in kidney transplant recipients with AA amyloidosis due to familial Mediterranean fever
Authors: Trabulus Sinan , Korkmaz Merve , Kaya Eda , Seyahi Nurhan
Published: July 2018

Background

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent serosal inflammation with fever, which can result in amyloid deposition. Anti‐interleukin‐1 drugs emerge as a therapeutic option for colchicine‐resistant patients. In this study, we aimed to document our experience with canakinumab use in kidney transplant recipients who developed AA amyloidosis due to FMF.

Methods

A total of nine patients with FMF amyloidosis treated with canakinumab were enrolled. Laboratory and clinical data were collected from the patient files, electronic database of the hospital and with interviews.

Results

Five of the patients were male and four were female (median age: 33, range: 27‐62 years). All of the patients had rapid or gradual disappearance of FMF attacks. The following changes in the laboratory parameters were observed before and after the treatment: C‐reactive protein: 18.31 ± 13.58 mg/L vs 9.98 ± 11.66 mg/L, creatinine clearance: 45.27 ± 21.5 mL/min vs 50.71 ± 22.48 mL/min, and 24‐hour proteinuria: 2381.8 ± 3910.4 mg vs 710.0 ± 1117.5 mg; there were no statistically significant differences on those parameters. One patient developed a reaction to injection while another showed symptoms of Cytomegalovirus pneumonia.

Conclusion

Canakinumab can be considered as a safe and efficient drug in preventing the FMF attacks in kidney transplant recipients.
Impact of pharyngeal endoscopic tip placement and water flushing interval on upper respiratory tract disorders in horses undergoing overground endoscopy
Authors: McGivney C. L. , Sweeney J. , Gough K. F. , Hill E. W. , Katz L. M.
Published: July 2018

Background

Endoscopic tip placement in the pharynx and water flushing interval (FI) may affect exercising upper respiratory tract (URT) endoscopic results.

Objectives

To determine associations between the endoscopic tip position in the pharynx and automatedFIwith overground endoscopic (OGE) results.

Study design

Randomised balanced 2X5 factorial design.

Methods

A total of n = 200 horses undergoingOGEwere randomly assigned into 10 groups (n = 20/group) of different automated endoscopicFIs (no flushing, 60, 120, 180, 240 s) with the endoscope tip positioned either rostrally (position A) or caudally (position B) in the pharynx. Endoscopic videos were analysed and allURTabnormalities graded using published scales. Disorders with ≤10% prevalence were excluded from the final analysis with only arytenoid asymmetry at exercise (AAex), vocal fold collapse (VFC), palatal dysfunction (PD) and medial deviation of the aryepiglottic folds (MDAF) included. The association of endoscope position andFIwithURTdisorders was assessed using ordinal regression models with P≤0.05 significant.

Results

Endoscope tip positioning was significantly associated withPDgrading (P = 0.002), with 63/100 horses diagnosed withPDin position A and 45/100 in position B. No other significant direct associations betweenURTdisease and endoscope tip position were identified, although interactions between exercise velocity and endoscope position affectedMDAFgrade.FIwas not directly associated with alterations in disorder grading, although interactions between exercise velocity andFIappeared to affectMDAFgrade.

Main limitations

The same horse was not evaluated under each test condition potentially resulting in sample bias. Interactions between disorders were not evaluated. The sample size was insufficient to conclusively explore relationships between all factors and disorder grading.

Conclusions

Position of the endoscope tip within the pharynx appears to affect grading ofPDduringOGEexamination. Exercise velocity may affectMDAFgrade through interactions with endoscope position andFI.
Characterizing a pH‐switch anti‐C5 antibody as a tool for human and mouse complement C5 purification and cross‐species inhibition of classical and reactive lysis
Authors: Zelek Wioleta M. , Stott Matthew , Walters David , Harris Claire L. , Morgan B. Paul
Published: July 2018

C5 plays a major role in complement activation; C5 convertase cleaves C5 into the pro‐inflammatory C5a, and C5b, the nidus for the formation of the lytic membrane attack complex. C5 is a major target for anti‐complement drugs, necessitating better methods for the study of C5 function. Purification of C5 is complicated; classical methods involve precipitation or pH shifts that result in functional loss and low yield. We here present a method for C5 purification using a novel anti‐C5 monoclonal antibody (mAb); RO7112689 (C5i mAb, SKY59), pH‐switch engineered to induce antibody–antigen dissociation in the acidic endosome (~ pH 5·5). RO7112689 was bound on an affinity column; applied serum was completely depleted of C5. Elution at pH 5 produced fully active C5 at 98% yield. The mAb also bound C5b in the C5b6 complex, preventing C5b6 binding to target membranes and enabling purification of C5b6 from activated serum. RO7112689 inhibited C5 in mouse serum and efficiently purified mouse C5. Used as capture, RO7112689 produced sensitive and specific assays for human and mouse C5. This novel antibody enables efficient production of intact, fully active, pure human and mouse C5, and quantification of C5 in these species. The demonstration that RO7112689 binds C5b6 adds an additional mechanism of membrane attack complex inhibition by this mAb.
Low gallium‐content, dysprosium III‐doped, Ge–As–Ga–Se chalcogenide glasses for active mid‐infrared fiber optics
Authors: Tang Zhuoqi , Furniss David , Neate Nigel C. , Benson Trevor M. , Seddon Angela B.
Published: July 2018

A systematic investigation is presented, for the first time, of a 1000 ppmw (parts per million, by weight) Dy3+‐doped Ge–As–Ga–Se chalcogenide glass series, with a fixed low Ga content of 1 atomic% (at. %), suitable for active mid‐infrared fiber optics. Seven glasses constitute the series, which have increasing average coordination number from 2.49 to 2.61, in steps of 0.02, with the GeSe2, As2Se3, and Ga2Se3 stoichiometries kept. Glass formation is confirmed using X‐ray diffraction and differential scanning calorimetry. Fourier transform infrared spectroscopy is reported for the series. Parallel plate viscometry enables prediction of fiber‐drawing temperatures and, with differential thermal analysis, determines the potential for fiber fabrication. X‐ray diffraction of samples after parallel‐plate viscometry shows that Ge25As9Ga1Se65 (at. %) alone, in the glass‐series, devitrifies to form the single‐crystalline phase: monoclinic‐GeSe2; scanning electron microscope imaging suggests that this phase is both surface and bulk grown. Overall, the recommended host glass at. % compositions for doping with rare‐earth ions and drawing to active mid‐infrared fiber are: Ge17.5As18Ga1Se63.5, Ge15As21Ga1Se63, and Ge12.5As24Ga1Se62.5.
Impact of hepatocellular carcinoma aetiology and liver function on the benefit of surveillance: A novel approach for the adjustment of lead‐time bias
Authors: Toyoda Hidenori , Kumada Takashi , Tada Toshifumi , Mizuno Kazuyuki , Hiraoka Atsushi , Tsuji Kunihiko , Ishikawa Toru , Akita Tomoyuki , Tanaka Junko
Published: July 2018

Background & Aims

Surveillance reportedly has benefit on survival in patients with hepatocellular carcinoma (HCC), even after adjustment for lead‐time bias. However, previous adjustment for lead‐time bias using tumour volume doubling time (TVDT) had inherent problem in accuracy. We evaluated survival benefit of HCC surveillance with newly developed approach for adjusting lead‐time bias. In addition, survival benefit was evaluated according to HCC aetiology and liver function.

Methods

A total of 3899 patients were studied. TVDT was calculated in 255 study patients with ≥2 tumour size measurements before the diagnosis of HCC. Adjusted survival time was calculated based on TVDT, as the time from when HCC was assumed to be 5 mm to death or last follow‐up. Survival rates based on this adjusted survival time were compared between the surveillance and nonsurveillance groups and categorized by HCC aetiology and liver function.

Results

Calculated TVDT varied widely by study patients (median 141.9, IQR, 73.1‐261.7 days). Survival rates based on adjusted survival time were higher in the surveillance group overall and by patients HCC aetiology. Whereas adjusted survival rates were higher in the surveillance group in Child‐Pugh class A patients, the survival benefit was smaller in Child‐Pugh class B patients and not statistically significant in Child‐Pugh class C patients.

Conclusions

The survival benefit of surveillance for patients with HCC was demonstrated after adjustment for lead‐time bias with novel, more accurate methodology. However, the benefits differed based on liver function and may vary largely by patients because of wide variation in TVDT.
Risk factors and impact of allergic bronchopulmonary aspergillosis in Pseudomonas aeruginosa‐negative CF patients
Authors: De Baets Frans , De Keyzer Linde , Van daele Sabine , Schelstraete Petra , Van Biervliet Stephanie , Van Braeckel Eva , Thomas Muriel , Wanyama Simeon S.
Published: July 2018

Background

Allergic bronchopulmonary aspergillosis (ABPA) is a major complication in cystic fibrosis (CF) patients. Risk factors for ABPA and clinical deterioration in CF patients, negative for Pseudomonas aeruginosa (Pa), were explored.

Methods

We performed a retrospective case‐control study in 73 Pa‐negative patients. Each patient was matched with 2 controls for age, gender, pancreas sufficiency, DeltaF508 mutation (homozygous or heterozygous), and Pa colonization.

Results

Median FEV1 at the year of diagnosis (index year) was significantly lower in patients with ABPA. The median of cumulative values of FEV1 and FVC before the index year was not significantly different. After the index year, the median of cumulative data for FEV1 and FVC was significantly lower; there were significantly more hospitalization days and more IV antibiotic days compared to controls. Comparing pre‐ and post‐index year data in patients with ABPA, significantly more hospitalization days and more IV antibiotic days were observed after the index year. During the period preceding the index year, significantly more ABPA patients were treated with rhDNase and inhaled corticosteroids.

Conclusions

Bronchial damage cannot be considered as a facilitating factor for ABPA. ABPA causes a significant increase in bronchial damage. In patients with ABPA, further bronchial damage can be controlled by an increase in hospitalization days and use of IV antibiotics. rhDNase and inhaled corticosteroids were associated with the development of ABPA.
Maize lateral root developmental plasticity induced by mild water stress. I: Genotypic variation across a high‐resolution series of water potentials
Authors: Dowd Tyler G. , Braun David M. , Sharp Robert E.
Published: July 2018

Lateral root developmental plasticity induced by mild water stress was examined across a high‐resolution series of growth media water potentials (Ψw) in two genotypes of maize. The suitability of several media for imposing near‐stable Ψw treatments on transpiring plants over prolonged growth periods was assessed. Genotypic differences specific to responses of lateral root growth from the primary root system occurred between cultivars FR697 and B73 over a narrow series of water stress treatments ranging in Ψw from −0.25 to −0.40 MPa. In FR697, both the average length and number of first‐order lateral roots were substantially enhanced at a Ψw of −0.25 MPa compared with well‐watered controls. These effects were separated spatially, occurring primarily in the upper and lower regions of the axial root, respectively. Furthermore, first‐order lateral roots progressively increased in diameter with increasing water stress, resulting in a maximum 2.3‐fold increase in root volume at a Ψw of −0.40 MPa. In B73, in contrast, the length, diameter, nor number of lateral roots was increased in any of the water stress treatments. The genotype‐specific responses observed over this narrow range of Ψw demonstrate the necessity of high‐resolution studies at mild stress levels for characterization of lateral root developmental plasticity.
Double Effect Electron Transfer System in the AgBr/ZnO Composite with Enhanced Photocatalytic Degradation Performance against 3‐Chlorophenol under Visible Light Irradiation
Authors: Vaizoğullar Ali İmran
Published: July 2018

Visible light‐driven novel and highly efficient AgBr/ZnO photocatalysts were synthesized by a facile precipitation and dehydration methods. The synthesized samples were characterized using scanning electron microscope (SEM), X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), UV‐Visible diffuse reflectance spectroscopy (UV‐Vis DRS), and photoluminescence (PL) techniques. Within various combinations of AgBr and ZnO components in the composites, 1AgBr/ZnO showed higher photocatalytic activity against 3‐chlorophenol (3‐CP). UV‐Vis DRS spectra showed that the absorbance of AgBr/ZnO was higher than pure ZnO in the visible light region. The PL results showed that efficient inhibition of the generated electron/hole pairs has occurred during the degradation process due to the formation of heterojunctions. The forming of metallic Ag0 by photogenerated electrons, which captures Ag+ ions, could act as an interfacial charge transmission bridge in the AgBr/ZnO composite. These results provided an important insight into the plasmonic Ag particles to obtain an efficient visible light‐driven photocatalyst. In addition, the possible mechanism of charge transfers and separation of electron/hole pairs were also evaluated in detail.
Effects of football simulated fatigue on neuromuscular function and whole‐body response to disturbances in balance
Authors: Behan Fearghal P. , Willis Scott , Pain Matt T.G. , Folland Jonathan P.
Published: July 2018

The effect of football‐specific fatigue on explosive neuromuscular performance and dynamic balance has received little attention in the literature despite the potential consequences for injury risk. This study aimed to investigate the effect of fatigue induced by simulated football match play on maximal and explosive knee flexor (KF) and knee extensor (KE) torque, and thus the maximal and explosive KF/KE ratio, as well as the effect of fatigue induced by simulated football match play on whole‐body response to disturbances in balance. Fifteen male team sports players (mean ± SD: age 24.2 ± 4.2 years; stature 1.79 ± 0.09 m; body mass, 77.3 ± 10.7 kg) underwent ~90 minutes of the modified Loughborough Intermittent Shuttle Test (LIST; fatiguing exercise condition) or seated rest (control condition) on separate days. Maximal and explosive isometric KF and KE voluntary torque (MVT/EVT) were assessed pre‐ and post‐condition. Maximal and explosive KF/KE ratios were calculated. Center of mass (COM) response (displacement) to unexpected anterior and posterior platform perturbations were also assessed pre‐ and post‐condition. Football simulated fatigue resulted in reduced KF (15%) and KE (12%) MVT (P ≤ 0.002) but was not found to reduce EVT of either muscle group, or explosive KF/KE ratio. Football simulated fatigue resulted in impaired balance response (11% increase in COM displacement) to unexpected perturbation in the posterior (P = 0.002) but not the anterior direction. Impaired response to dynamic disturbances in balance, rather than explosive torque or changes in muscle balance (H/Q ratios), may be a contributory factor toward increased injury risk in the latter portion of football games, and likely highlights the influence of fatigue on sensory/proprioceptive processes.
Golimumab induction and maintenance for moderate to severe ulcerative colitis: results from GO-COLITIS (Golimumab: a Phase 4, UK, open label, single arm study on its utilization and impact in ulcerative Colitis)
Authors: Probert Christopher SJ , Sebastian Shaji , Gaya Daniel R , Hamlin P John , Gillespie Gillian , Rose Anita , Tate Helen , Wheeler Colin , Irving Peter M
Published: July 2018

Objective

GO-COLITIS aimed to measure the effectiveness of subcutaneous golimumab in tumour necrosis factor-α antagonist–naive patients with moderate to severe ulcerative colitis (UC) despite conventional treatment.

Design

GO-COLITIS was an open label, single arm, phase 4 study with a pragmatic design which reflected UK clinical practice. Adult patients were eligible if diagnosed with UC ≥3 months, partial Mayo score (PMS) 4–9. Patients received subcutaneous golimumab induction (200 mg initially and 100 mg at week 2) followed at week 6 by 50 mg or 100 mg (depending on weight) every 4 weeks until week 54 with a 12-week follow-up. Efficacy was measured by PMS at baseline, week 6, 30, 54 and 66. Health-related quality of life (HRQoL; Inflammatory Bowel Disease Questionnaire (IBDQ) and EuroQol Group 5 Dimensions Health Questionnaire (EQ-5D)) was assessed at baseline, week 6 and week 54. All safety adverse events (AEs) were recorded.

Results

207 patients were enrolled and 205 received golimumab (full analysis set (FAS)205). At week 6, 68.8% (95% CI 62.0% to 75.1%) and 38.5% (95% CI 31.8% to 45.6%) of patients were in response and remission, respectively, using PMS. At the end of the induction phase, 140/141 patients in clinical response continued into the maintenance phase (Maintenance FAS). Sustained clinical response through week 54 was achieved in 51/205 (24.9%) of the FAS205 population and 51/140 (36.4%) of the Maintenance FAS population. Statistically significant improvements from baseline to week 6 were observed for the IBDQ total score and for each IBDQ domain score (bowel symptoms, emotional function, systemic symptoms and social function), as well as the EQ-5D index score and associated visual analogue scale score (p<0.0001). Improvement of HRQoL was sustained through week 54. Serious AEs leading to treatment discontinuation occurred in 8.8% of patients.

Conclusion

In this study measuring patient-reported outcomes in patients with moderate to severe UC, golimumab induced and maintained response as measured by PMS and significantly improved quality of life measures.

Trial registration number

NCT02092285; 2013-004583-56.
Risk factors and risk factor cascades for communicable disease outbreaks in complex humanitarian emergencies: a qualitative systematic review
Authors: Hammer Charlotte Christiane , Brainard Julii , Hunter Paul R
Published: July 2018

Background

Communicable diseases are a major concern during complex humanitarian emergencies (CHEs). Descriptions of risk factors for outbreaks are often non-specific and not easily generalisable to similar situations. This review attempts to capture relevant evidence and explore whether it is possible to better generalise the role of risk factors and risk factor cascades these factors may form.

Methods

A systematic search of the key databases and websites was conducted. Search terms included terms for CHEs (United Nations Office for the Coordination of Humanitarian Affairs definition) and terms for communicable diseases. Due to the types of evidence found, a thematic synthesis was conducted.

Results

26 articles met inclusion criteria. Key risk factors include crowded conditions, forced displacement, poor quality shelter, poor water, sanitation and hygiene, lack of healthcare facilities and lack of adequate surveillance. Most identified risk factors do not relate to specific diseases, or are specific to a group of diseases such as diarrhoeal diseases and not to a particular disease within that group. Risk factors are often listed in general terms but are poorly evidenced, not contextualised and not considered with respect to interaction effects in individual publications. The high level of the inter-relatedness of risk factors became evident, demonstrating risk factor cascades that are triggered by individual risk factors or clusters of risk factors.

Conclusions

CHEs pose a significant threat to public health. More rigorous research on the risk of disease outbreaks in CHEs is needed, from a practitioner and from an academic point of view.
Accountability mechanisms and the value of relationships: experiences of front-line managers at subnational level in Kenya and South Africa
Authors: Nxumalo Nonhlanhla , Gilson Lucy , Goudge Jane , Tsofa Benjamin , Cleary Susan , Barasa Edwine , Molyneux Sassy
Published: July 2018

Resource constraints, value for money debates and concerns about provider behaviour have placed accountability ‘front and centre stage’ in health system improvement initiatives and policy prescriptions. There are a myriad of accountability relationships within health systems, all of which can be transformed by decentralisation of health system decision-making from national to subnational level. Many potential benefits of decentralisation depend critically on the accountability processes and practices of front-line health facility providers and managers, who play a central role in policy implementation at province, county, district and facility levels. However, few studies have examined these responsibilities and practices in detail, including their implications for service delivery. In this paper we contribute to filling this gap through presenting data drawn from broader ongoing research collaborations between researchers and health managers in Kenya and South Africa. These collaborations are aimed at understanding and strengthening day-to-day micropractices of health system governance, including accountability processes. We illuminate the multiple directions and forms of accountability operating at the subnational level across three sites. Through detailed illustrative examples we highlight some of the unintended consequences of bureaucratic forms of accountability, the importance of relational elements in enabling effective bureaucratic accountability, and the ways in which front-line managers can sometimes creatively draw upon one set of accountability requirements to challenge another set to meet their goals. Overall, we argue that interpersonal interactions are key to appropriate functioning of many accountability mechanisms, and that policies and interventions supportive of positive relationships should complement target-based and/or audit-style mechanisms to achieve their intended effects. Where this is done systematically and across key elements and actors of the health system, this offers potential to build everyday health system resilience.
Patient safety initiatives in obstetrics: a rapid review
Authors: Antony Jesmin , Zarin Wasifa , Pham Ba’ , Nincic Vera , Cardoso Roberta , Ivory John D , Ghassemi Marco , Barber Sarah Louise , Straus Sharon E , Tricco Andrea C
Published: July 2018

Objectives

This review was commissioned by WHO, South Africa-Country office because of an exponential increase in medical litigation claims related to patient safety in obstetrical care in the country. A rapid review was conducted to examine the effectiveness of quality improvement (QI) strategies on maternal and newborn patient safety outcomes, risk of litigation and burden of associated costs.

Design

A rapid review of the literature was conducted to provide decision-makers with timely evidence. Medical and legal databases (eg, MEDLINE, Embase, LexisNexis Academic, etc) and reference lists of relevant studies were searched. Two reviewers independently performed study selection, abstracted data and appraised risk of bias. Results were summarised narratively.

Interventions

We included randomised clinical trials (RCTs) of QI strategies targeting health systems (eg, team changes) and healthcare providers (eg, clinician education) to improve the safety of women and their newborns. Eligible studies were limited to trials published in English between 2004 and 2015.

Primary and secondary outcome measures

RCTs reporting on patient safety outcomes (eg, stillbirths, mortality and caesarean sections), litigation claims and associated costs were included.

Results

The search yielded 4793 citations, of which 10 RCTs met our eligibility criteria and provided information on over 500 000 participants. The results are presented by QI strategy, which varied from one study to another. Studies including provider education alone (one RCT), provider education in combination with audit and feedback (two RCTs) or clinician reminders (one RCT), as well as provider education with patient education and audit and feedback (one RCT), reported some improvements to patient safety outcomes. None of the studies reported on litigation claims or the associated costs.

Conclusions

Our results suggest that provider education and other QI strategy combinations targeting healthcare providers may improve the safety of women and their newborns during childbirth.
Care pathway and organisational features driving patient experience: statistical analysis of large NHS datasets
Authors: Flott Kelsey , Darzi Ara , Mayer Erik
Published: July 2018

Objective

The aim of this study was to identify the care pathway and organisational factors that predict patient experience.

Design

Statistical analysis of large National Health Service (NHS) datasets.

Setting andparticipants

England; acute NHS organisational-level data.

Primary and secondary outcome measures

The relationship of care pathway and organisational variables to organisation-level patient experience.

Results

A framework of 18 care pathway and organisational variables were created based on the existing literature. 11 of these correlated to patient experience in univariate analyses. Multicollinearity tests resulted in 1 of the 11 variables holding a correlation to another variable larger than r=0.70. A significant multilinear regression equation, including the final 10 variables, was found (F(10,108)=6.214, p<0.00), with anR2of 0.365. Two variables were significant in predicting better in patient experience: Amount of support to clinical staff (beta=0.2, p=0.02) and the proportion of staff who would recommend the trust as a place to work or receive treatment (beta=0.26, p=0.01). Two variables were significant in predicting a negative impact on the patient’s rating of their experience: Number of patients spending over 4 hours from decision to admit to admission (beta=−1.99, p=0.03) and the percentage of estates and hotel services contracted out (beta=−0.23, p=0.01).

Conclusions

These results indicate that augmenting clinical support and investing in the mechanisms that facilitate positive staff experience is essential to delivering appropriate, informative and patient-centric care. Reducing wait times and the extent of external contracting within hospitals is also likely to improve patient ratings of experience. Understanding the relationship between patient experience and objective, measurable organisational features promote a more patient-centric interpretation of quality and compel a better use of patient experience feedback to drive improvement.
Barriers to uptake of referral services from secondary care to tertiary care and its associated factors in L V Prasad Eye Institute network in Southern India: a cross-sectional study
Authors: Khanna Rohit C , Kim Sujeong , Giridhar Pyda , Mettla Asha Latha , Marmamula Srinivas , Rao Gullapalli Nageswara
Published: July 2018

Objective

To examine barriers to the uptake of referral services from secondary care centres to higher level tertiary care centres.

Design

Cross-sectional study.

Setting

Secondary care hospital in Khammam District in the Telangana state of India.

Participants

Nine hundred and three patients who were referred from a secondary care centre to tertiary care centres between June 2011 and December 2012, were over the age of 18 and lived within 50 km of the secondary care centre were identified. Six hundred and sixteen (68.2%) of these patients were successfully contacted, and 611 (99%) of those contacted consented to participation in the study.

Interventions

Those who attended at higher centres after referral (compliant) and those who failed to attend (non-compliant) were interviewed with a standard questionnaire designed for the study.

Primary and secondary outcome measures

Outcome measures were barriers to the uptake of eye care services for the non-compliant participants and the associated risk factors for non-compliance.

Results

Of the contacted patients, 418 (68.4%) were compliant and 193 (31.6%) were non-compliant. The mean age of interviewed patients was 48.4 years (SD: 17.9 years) and 365 (59.7%) were male. Of those who did not comply with their referral, the major identified barriers were ‘cannot afford treatment cost’ (30%) and ‘able to see adequately’ (20.7%). Multivariable analysis showed that participants in the non-compliant group were more likely to have had only one prior visit to the centre (OR: 2.5, 95% CI 1.6 to 3.9), be referred for oculoplastic services (OR: 3.0, 95% CI 1.0 to 8.8) and to be the main earning member of the family (OR: 1.9, 95% CI 1.2 to 2.8).

Conclusions

Non-compliance with referrals in this population is largely attributable to economic and attitudinal reasons. Focusing on these specific barriers and targeting groups at higher risk of non-compliance could potentially improve uptake of referral services.
Emotional reserve and prolonged post-concussive symptoms and disability: a Swedish prospective 1-year mild traumatic brain injury cohort study
Authors: Oldenburg Christian , Lundin Anders , Edman Gunnar , Deboussard Catharina Nygren , Bartfai Aniko
Published: July 2018

Objective

Prolonged post-concussive symptoms (PCS) affect a significant minority of patients withmild traumatic brain injury (mTBI). The aetiology is multifactorial depending on preinjury as well as peri-injury and postinjury factors. In this study, we examine outcome from an emotional reserve perspective.

Design

Prospective cohort study.

Setting

Patients were recruited from three emergency departments in major university hospitals in Stockholm, Sweden. Follow-up data were collected in an outpatient setting at one of the recruiting hospitals.

Participants

122 patients with a history of blunt head trauma (aged 15–65 years; admitted for mTBI within 24 hours after trauma (Glasgow Coma Scale score of 14–15, loss of consciousness <30 min and/or post-traumatic amnesia <24 hours). Exclusion criteria were other significant physical injury and other major neurological disorder, including previous significant head injury.

Procedure

Recruitment in three emergency departments. Initial assessments were made within 1 week after the injury. Patients were mailed the follow-up questionnaires 1 year postinjury.

Outcome measures

A psychiatric assessment was performed at 1 week post injury. The participants also completed a personality inventory, measures of psychological resilience, depression, anxiety and post-traumatic symptoms. One-year outcome was measured by the Rivermead Post Concussion Symptoms and the Rivermead Head Injury Follow-Up questionnaires.

Results

The psychiatric assessment revealed more symptoms of anxiety, depression and post-traumatic symptoms in the acute stage for patients who later developed PCS.

After 1 year, 94 participants were still in the programme (male/female 57/37) and 12% matched the extended criteria for PCS (≥3 symptoms and ≥2 disabilities). PCS patients reported more preinjury and concurrent psychiatric problems, lower level of functioning before the injury and experienced more stress. They showed higher somatic trait anxiety, embitterment, mistrust and lower level of psychological resilience than recovered participants.

Conclusion

Intrapersonal emotional reserve shape the emergence and persistence of PCS after mTBI.
Sipjeondaebo-tang in patients with breast cancer with fatigue: a protocol for a pilot, randomised, double-blind, placebo-controlled, cross-over trial
Authors: Cheon Chunhoo , Kang Sohyeon , Ko Youme , Kim Mia , Jang Bo-Hyoung , Shin Yong-Cheol , Ko Seong-Gyu
Published: July 2018

Introduction

Cancer-related fatigue is a frequent symptom in patients with cancer and one of the most distressing symptoms in patients with breast cancer. Sipjeondaebo-tang (Juzen-taiho-to in Japanese or Shi-Quan-Da-Bu-Tang in Chinese) is a widely used herbal medicine for the treatment of fatigue in Korea, China and Japan. The purpose of the present study is to evaluate the feasibility of Sipjeondaebo-tang for cancer-related fatigue.

Methods and analysis

The present study is a randomised, double-blind, placebo-controlled, cross-over study. Forty-eight patients with breast cancer who are indicated for doxorubicin and cyclophosphamide will be recruited. The participants will receive 3 g of Sipjeondaebo-tang or a placebo three times a day for 56 days. The primary outcome measurement is the change in the Brief Fatigue Inventory scores. The secondary outcome measurements include the changes in the Visual Analogue Scale (VAS) of fatigue, and quality of life measured by the European Organization for Research and Treatment of Cancer—QLQ-C30 and QLQ-BR23. VAS of fatigue will be measured on every visit, and other outcomes will be measured on visits 2, 4, 6 and 7. The total study period is 14 weeks.

Ethics and dissemination

This study has been approved by the Institutional Review Board of the Catholic Kwandong University International St Mary’s Hospital (reference IS16MNSI0011). The results of this study will be published in a peer-reviewed journal and presented at a scientific conference.

Trial registration number

NCT02858856; Pre-results.
Enhancing acute stroke services: a quality improvement project
Authors: McGrath Keith , Cunningham Nora , Moloney Elizabeth , O’Connor Margaret , McManus John , Peters Catherine , Lyons Declan
Published: July 2018

Background

In a busy stroke centre in Ireland, care for acute stroke was provided by a mixture of general physicians. In acute ischaemic stroke, speed is essential for good outcomes.

Aim

To improve acute stroke services and decrease door-to-needle (DTN) time to less than 60 min by December 2016 in patients with acute ischaemic stroke who are eligible for intravenous thrombolysis.

Design: A quality improvement (QI) project was undertaken in a 438 bed, acute, university hospital.

Methods

Mixture of qualitative and quantitative data collected. A process map and driver diagram were created. Interventions tested with Plan-Do-Study-Act cycles. Times compared between July and December 2015, January and July 2016, July and December 2016, when a new stroke team and pathway were introduced.

Results

Between July and December 2015, the total number of ischaemic strokes was 216. 17 were thrombolysed (7.8%). Median door-to-CT (DTCT) time was 36 min (range 21–88). Median DTN time was 99 min (range 52–239). Between July and December 2016, there were 214 ischaemic strokes. 29 were thrombolysed (13.5%). 9 were seen directly by the stroke team during normal hours. With stroke team involvement, median DTCT time was 34 min (range 14–60) and DTN time was 43.5 min (range 24–65).

Conclusions

This project led to a significant and sustained improvement in acute stroke care in our hospital with the use of quality improvement techniques. A comprehensive protocol, recurrent and ongoing staff education, and good communication helped to mitigate delays and further enhance care provided to patients presenting with stroke. The approach described may be valuable to the improvement of other services.’
Fair, just and compassionate: A pilot for making allocation decisions for patients requesting experimental drugs outside of clinical trials
Authors: Caplan Arthur L , Teagarden J Russell , Kearns Lisa , Bateman-House Alison S , Mitchell Edith , Arawi Thalia , Upshur Ross , Singh Ilina , Rozynska Joanna , Cwik Valerie , Gardner Sharon L
Published: July 2018

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or ‘preapproval’, access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients’ best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee (CompAC). Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice.
Idiopathic splenomegaly: a previously unrecognised cause of anaemia and thrombocytopenia in a dog
Authors: Kelly Darren , Craig Andrew , Juvet Florence
Published: July 2018

A nine-year-old female neutered Old English sheepdog was referred for investigation and treatment of moderate, non-regenerative anaemia and thrombocytopenia. Aside from the aforementioned changes on complete blood count (CBC), the only abnormality found during diagnostic investigation was marked, generalised splenomegaly. A cause for the anaemia, thrombocytopenia and splenomegaly was not found following initial investigation. Splenectomy was performed and histopathological analysis showed marked, diffuse, subacute-chronic congestion and intraparenchymal haemorrhage. There was no evidence of neoplastic change. The splenic vasculature appeared normal during coeliotomy and torsion was not present. The findings of anaemia and thrombocytopenia, along with the histopathological changes found in the spleen, are similar to those found in people diagnosed with idiopathic splenomegaly. The dog recovered well from anaesthesia and was discharged the following day. Repeat CBCs over 12 months postsurgery showed results within normal limits, and no clinical signs had been reported by the owners.
Predictive Ability of Novel Cardiac Biomarkers ST2, Galectin‐3, and NT‐ProBNP Before Cardiac Surgery
Authors: Polineni Sai , Parker Devin M. , Alam Shama S. , Thiessen‐Philbrook Heather , McArthur Eric , DiScipio Anthony W. , Malenka David J. , Parikh Chirag R. , Garg Amit X. , Brown Jeremiah R.
Published: July 2018

Background

Current preoperative models use clinical risk factors alone in estimating risk of in‐hospital mortality following cardiac surgery. However, novel biomarkers now exist to potentially improve preoperative prediction models. An assessment of Galectin‐3, N‐terminal pro b‐type natriuretic peptide (
NT
‐Pro
BNP
), and soluble
ST
2 to improve the predictive ability of an existing prediction model of in‐hospital mortality may improve our capacity to risk‐stratify patients before surgery.

Methods and Results

We measured preoperative biomarkers in the NNECDSG (Northern New England Cardiovascular Disease Study Group), a prospective cohort of 1554 patients undergoing coronary artery bypass graft surgery. Exposures of interest were preoperative levels of galectin‐3,
NT
‐Pro
BNP
, and
ST
2. In‐hospital mortality and adverse events occurring after coronary artery bypass graft were the outcomes. After adjustment,
NT
‐Pro
BNP
and
ST
2 showed a statistically significant association with both their median and third tercile categories with
NT
‐Pro
BNP
odds ratios of 2.89 (95% confidence interval [
CI
]: 1.04–8.05) and 5.43 (95%
CI
: 1.21–24.44) and
ST
2 odds ratios of 3.96 (95%
CI
: 1.60–9.82) and 3.21 (95%
CI
: 1.17–8.80), respectively. The model receiver operating characteristic score of the base prediction model (0.80 [95%
CI
: 0.72–0.89]) varied significantly from the new multi‐marker model (0.85 [95%
CI
: 0.79–0.91]). Compared with the Northern New England (
NNE
) model alone, the full prediction model with biomarkers
NT
‐pro
BNP
and
ST
2 shows significant improvement in model classification of in‐hospital mortality.

Conclusions

This study demonstrates a significant improvement of preoperative prediction of in‐hospital mortality in patients undergoing coronary artery bypass graft and suggests that biomarkers can be used to identify patients at higher risk.