bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming Challenges to Evidence‐Based Policy Development in a Large, Integrated Delivery System
Authors: Frakt Austin B. , Prentice Julia C. , Pizer Steven D. , Elwy A. Rani , Garrido Melissa M. , Kilbourne Amy M. , Atkins David
Published: June 2018

Objective

To describe a new Veterans Health Administration (VHA) program to foster the learning health system paradigm by rigorously evaluating health care initiatives and to report key lessons learned in designing those evaluations.

Principal Findings

The VHA's Quality Enhancement Research Initiative and its Health Services Research and Development Service are cooperating on several large, randomized program evaluations aimed at improving the care veterans receive and the efficiency with which it is delivered. The evaluations we describe involve collaborative design, outcomes assessment, and implementation science through partnerships between VHA operations and researchers. We review key factors to assess before committing to an evaluation. In addition to traditional design issues (such as ensuring adequate power and availability of data), these include others that are easily overlooked: the stability of intervention financing, means of controlling and commitment to adhering to randomized roll‐out, degree of buy‐in from key implementation staff, and feasibility of managing multiple veto points for interventions that span several programs, among others.

Conclusions

Successful program implementation and rigorous evaluation require resources, specialized expertise, and careful planning. If the learning health system model is to be sustained, organizations will need dedicated programs to prioritize resources and continuously adapt evaluation designs.
Morphological description of male genital organs of Marca's marmoset (Mico marcai)
Authors: de Siqueira Gustavo Henrique Lima , Silva Felipe Ennes , Santana Marcelo Ismar Silva
Published: June 2018

Morphological characterisation of the genital organs of primates may bring significant contributions to the understanding of different reproductive behaviours and support new conservation strategies. However, relevant or detailed descriptions of genital morphology of several primate species are still lacking. This study describes the gross and microscopic anatomy of the internal and external genitalia of Marca's marmoset (Mico marcai). The same organs described in other primate species were identified here, but some anatomical particularities were detected, such as absence of a dartos tunic, presence of a vas deferens ampulla, absence of spongious erectile tissue in the pelvic urethra, separation of prostate gland lobes by a longitudinal sulcus and lack of septation in the corpus cavernosus and spongiosus at the level of the shaft and free portion of the penis. Keratinised type 1 spicules arising from epidermal or dermal projections were found in the free portion of the penis. Microscopic analysis revealed a small bone (baculum) consisting of peripheral compact bone and a central, non‐ossified area filled with vascular tissue at the distal end of this portion of the penis. Results of this study may support further comparative studies of primates' reproductive ecology.
Impact of an integrated diabetes service involving specialist outreach and primary health care on risk factors for micro‐ and macrovascular diabetes complications in remote Indigenous communities in Australia
Authors: Hotu Cheri , Rémond Marc , Maguire Graeme , Ekinci Elif , Cohen Neale
Published: June 2018

Objective

To determine the impact of an integrated diabetes service involving specialist outreach and primary health care teams on risk factors for micro‐ and macrovascular diabetes complications in three remote Indigenous Australian communities over a 12‐month period.

Design

Quantitative, retrospective evaluation.

Setting

Primary health care clinics in remote Indigenous communities in Australia.

Participants

One‐hundred‐and‐twenty‐four adults (including 123 Indigenous Australians; 76.6% female) with diabetes living in remote communities.

Main outcome measures

Glycosylated haemoglobin, lipid profile, estimated glomerular filtration rate, urinary albumin : creatinine ratio and blood pressure.

Results

Diabetes prevalence in the three communities was high, at 32.8%. A total of 124 patients reviewed by the outreach service had a median consultation rate of 1.0 by an endocrinologist and 0.9 by a diabetes nurse educator over the 12‐month period. Diabetes care plans were made in collaboration with local primary health care services, which also provided patients with diabetes care between outreach team visits. A significant reduction was seen in median (interquartile range) glycosylated haemoglobin from baseline to 12 months. Median (interquartile range) total cholesterol was also reduced. The number of patients prescribed glucagon‐like peptide‐1 analogues and dipeptidyl peptidase‐4 inhibitors increased over the 12 months and an increase in the number of patients prescribed insulin trended towards statistical significance.

Conclusion

A collaborative health care approach to deliver diabetes care to remote Indigenous Australian communities was associated with an improvement in glycosylated haemoglobin and total cholesterol, both important risk factors, respectively, for micro‐ and macrovascular diabetes complications.
What do mental health workers in the bush think about mental health nurse prescribing? A cross‐sectional study
Authors: Muyambi Kuda , McPhail Ruth , Cronin Kathryn , Gillam Marianne , Martinez Lee , Dennis Shaun , Bressington Daniel , Gray Richard , Jones Martin
Published: June 2018

Introduction

Relatively few psychiatrists live and work in rural South Australia. The rural GP is an essential component of support for people with mental health problems. However, considerable GP maldistribution between rural and metropolitan Australia still exists. Thus, accessing health services, including medication, becomes challenging for rural communities. Extending mental health nurse prescribing could be a strategy to build additional capacity to complement the GPs and psychiatrists who practice in rural South Australia. Until now, no studies have examined mental health workers’ attitudes towards nurse prescribing in rural Australia.

Objective

To examine the attitudes of rural and remote South Australian mental health workers about mental health nurse prescribing.

Design/method

A cross‐sectional survey assessing mental health workers’ attitudes to mental health nurse prescribing.

Setting

The study was conducted across South Australia, excluding metropolitan Adelaide.

Participants

Mental health workers employed by the Country Health South Australia Local Health Network for Mental Health.

Results

Of the 289 potential participants, 93 (32%) responded and were included in this study. All the respondents reported positive attitudes towards mental health nurse prescribing. However, they expressed concerns about safety, educational preparation and supervision structures.

Conclusion

The attitudes of rural South Australian mental health workers are not a barrier to mental health nurse prescribing. The implementation and sustainability of mental health nurse prescribing will require additional staff training in psychopharmacology and a governance framework to assure quality and safety. Policy‐makers need to focus their attention on the uptake of mental health nurse prescribing in parts of Australia that struggle to attract and retain psychiatrists.
Ultra‐short heart rate variability recording reliability: The effect of controlled paced breathing
Authors: Melo Hiago M. , Martins Thiago C. , Nascimento Lucas M. , Hoeller Alexandre A. , Walz Roger , Takase Emílio
Published: June 2018

Background

Recent studies have reported that Heart Rate Variability (HRV) indices remain reliable even during recordings shorter than 5 min, suggesting the ultra‐short recording method as a valuable tool for autonomic assessment. However, the minimum time‐epoch to obtain a reliable record for all HRV domains (time, frequency, and Poincare geometric measures), as well as the effect of respiratory rate on the reliability of these indices remains unknown.

Methods

Twenty volunteers had their HRV recorded in a seated position during spontaneous and controlled respiratory rhythms. HRV intervals with 1, 2, and 3 min were correlated with the gold standard period (6‐min duration) and the mean values of all indices were compared in the two respiratory rhythm conditions.

Results

rMSSD and SD1 were more reliable for recordings with ultra‐short duration at all time intervals (r values from 0.764 to 0.950, p < 0.05) for spontaneous breathing condition, whereas the other indices require longer recording time to obtain reliable values. The controlled breathing rhythm evokes stronger r values for time domain indices (r values from 0.83 to 0.99, p < 0.05 for rMSSD), but impairs the mean values replicability of domains across most time intervals. Although the use of standardized breathing increases the correlations coefficients, all HRV indices showed an increase in mean values (t values from 3.79 to 14.94, p < 0.001) except the RR and HF that presented a decrease (t = 4.14 and 5.96, p < 0.0001).

Conclusion

Our results indicate that proper ultra‐short‐term recording method can provide a quick and reliable source of cardiac autonomic nervous system assessment.
Assessment of acetabular version in total hip arthroplasty: an application of Widmer's technique in a regional setting
Authors: Trieu Jason , Hadden Alexandra E. F. , Sutherland Alasdair G.
Published: June 2018

Background

Acetabular prosthesis positioning in total hip arthroplasty is important in reducing the risk of dislocation. Assessment of version by computed tomography scan is expensive and involves a large radiation dose. We wished to assess the value of Widmer's technique, utilizing readily available radiographs, to determine cup anteversion.

Methods

Patients who underwent primary total hip arthroplasty by the senior author (AGS) at a single regional hospital over a 5‐year period were eligible for inclusion. Measurements were performed using the technique described by Widmer, utilizing standard post‐operative radiographs. Statistical analysis was undertaken in SPSS v22. Significance was accepted at P < 0.05.

Results

Assessment included 109 hips in 99 patients; 63 hips with cemented cups and 46 hips with uncemented cups. Mean acetabular anteversion in the cemented group was 11.9° (0–27.7, SD: 7) and in the uncemented group was 14.1° (10.3–32.7, SD: 7.1); this difference trended towards statistical significance (P = 0.09). Test–retest measurements showed high degree of correlation (Pearson test: 0.927, P < 0.001). There were 96 of 109 hips positioned in the Lewinnek safe zone of 5–25° anteversion. The crude dislocation rate in our cohort was 6.4% (7 of 109 hips) with all dislocations occurring in hips placed in the safe zone.

Conclusion

Widmer's technique is a reliable method for calculating acetabular version in a regional hospital setting and offers the individual surgeon a ready technique of personal quality control. Cup version was not a significant factor contributing to dislocation rates in our series.
Comparative assessment of intraocular inflammation following standard or heavy silicone oil tamponade: a prospective study
Authors: Semeraro Francesco , Russo Andrea , Morescalchi Francesco , Gambicorti Elena , Vezzoli Sara , Parmeggiani Francesco , Romano Mario R. , Costagliola Ciro
Published: June 2018

Purpose

To evaluate the inflammation associated with the use of standard silicone oil (polydimethylsiloxane; PDMS) and heavy silicone oil (HSO) Densiron‐68™ in patients undergoing vitrectomy for retinal detachment.

Materials and Methods

A prospective study was performed involving 35 patients scheduled to undergo vitrectomy for retinal detachment. Patients received PDMS or Densiron‐68™ HSO according to superior or inferior retinal localization of the tears, respectively. For assessing the inflammation, prostaglandin E2 (PGE2) and interleukin‐1α (IL‐1α) levels were evaluated in the aqueous.

Results

Thirty‐five eyes of 35 patients completed the study: 20 eyes received HSO, and 15 eyes received PDMS. The mean aqueous PGE2 level was significantly higher in HSO patients than in PDMS patients (869.16 ± 242.83 pg/ml versus 369.38 ± 209.7 pg/ml, respectively; p < 0.0001). The mean aqueous IL‐1α level was also significantly higher in HSO patients than in PDMS patients (81.40 ± 36.9 pg/ml versus 40.8 ± 32.5 pg/ml, respectively; p = 0.002). In HSO, a moderate positive correlation between the endotamponade duration and both PGE2 (r = 0.44; p = 0.05) and IL‐1α (r = 0.48; p = 0.033) levels was observed. In PDMS, a strong positive correlation between the endotamponade duration and both PGE2 (r = 0.89; p < 0.0001) and IL‐1α (r = 0.68; p = 0.006) levels was observed.

Conclusion

Although both HSO and PDMS yielded favourable success rates in the surgical treatment of complicated retinal detachments, HSO triggered a more severe inflammatory reaction, in a time‐dependent manner.
Extrauterine growth restriction was associated with short stature and thinness in very low birthweight infants at around six years of age
Authors: Takayanagi Toshimitsu , Shichijo Akinori , Egashira Masakazu , Egashira Tomoko , Mizukami Tomoko
Published: June 2018

Aim

The effect that intrauterine or extrauterine growth restriction (EUGR) had on the build of very low birthweight (VLBW) infants was investigated before Japanese children started school.

Method

Between 2005 and 2017, the National Hospital Organization, Saga, Japan, carried out preschool checks on 322 children born with a VLBW at approximately six years of age. Growth restriction was defined as being born small for gestational age (SGA) or EUGR if they were born at term. The prevalence of short stature, thinness and obesity was determined, and associations between SGA or EUGR and subsequent body build were investigated.

Results

In this study, 77 of 322 (23.9%) infants were SGA and 153 of 322 (47.5%) were EUGR: 14 of 77 (18.2%) SGA infants caught up in growth to the 169 non‐EUGR infants, while 90 of 245 (36.7%) appropriate for gestational age infants subsequently demonstrated EUGR. There were 38 (11.8%) short stature, 38 (11.8%) thin and six (1.9%) obese subjects in the total cohort and growth hormone deficiencies in nine (2.8%) cases. We found significant associations between EUGR and both short stature and thinness.

Conclusion

Extrauterine growth restriction was significantly associated with short stature and thinness in VLBW infants at around six years, irrespective of the degree of SGA.
Senescence mirrors the extent of liver fibrosis in chronic hepatitis C virus infection
Authors: Wandrer F. , Han B. , Liebig S. , Schlue J. , Manns M. P. , Schulze‐Osthoff K. , Bantel H.
Published: June 2018

Background

Chronic viral hepatitis is linked to fibrotic liver injury that can progress to liver cirrhosis with its associated complications. Recent evidence suggests a role of senescence in liver fibrosis, although the senescence regulators contributing to fibrosis progression remain unclear.

Aim

To investigate the role of senescence and different senescence markers for fibrosis progression in patients with chronic hepatitis C virus (HCV) infection.

Methods

The expression of the cell cycle inhibitors p21, p27 and p16 as well as the senescence markers p‐HP1γ and γ‐H2AX was analysed in liver tissue with different fibrosis stages. Senescence‐associated chitotriosidase activity was measured in sera of HCV patients (n = 61) and age‐matched healthy individuals (n = 22).

Results

We found a remarkable up‐regulation of the cell cycle inhibitors and senescence markers in chronic HCV infection compared to healthy liver tissue. Liver tissue with relevant fibrosis stages (F2‐3) or cirrhosis (F4) revealed a significant increase in senescent cells compared to livers with no or minimal fibrosis (F0‐1). In cirrhotic livers, a significantly higher number of p‐HP1γ, p21 and p27 positive cells was detected compared to liver tissue with F2‐3 fibrosis. Importantly, we identified T‐cells as the dominant cell type contributing to increased senescence during fibrosis progression. Compared to healthy individuals, serum chitotriosidase was significantly elevated and correlated with histological fibrosis stages and liver stiffness as assessed by transient elastography.

Conclusions

Senescence of hepatic T‐cells is enhanced in chronic viral hepatitis and increases with fibrosis progression. Serological detection of senescence‐associated chitotriosidase might allow for the non‐invasive detection of relevant fibrosis stages.
Safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012, a novel potassium‐competitive acid blocker, in healthy male subjects
Authors: Sunwoo J. , Oh J. , Moon S. J. , Ji S. C. , Lee S. H. , Yu K.‐S. , Kim H. S. , Lee A. , Jang I.‐J.
Published: June 2018

Background

A novel potassium‐competitive acid blocker, DWP14012, is in clinical development as a potential alternative to proton pump inhibitors for the treatment of acid‐related diseases.

Aims

To evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012 in humans.

Methods

A randomised, double‐blind, double‐dummy, placebo‐ and active‐controlled, single‐ and multiple‐ascending dose (SAD and MAD, respectively) study was conducted in healthy male subjects without Helicobacter pylori infection. Subjects randomly received a single oral dose of 10‐320 mg DWP14012, esomeprazole (active comparator) or placebo in the SAD study (n = 72) and once daily doses of 20‐160 mg DWP14012, esomeprazole or placebo for 7 days in the MAD study (n = 48; 8:2:2). Tolerability was evaluated using a microRNA‐122 assay. Pharmacodynamics were evaluated through 24‐hour gastric pH monitoring, and pharmacokinetics were evaluated plasma and urine DWP14012 concentrations.

Results

DWP14012 was generally well tolerated. The liver toxicity of DWP14012 was not higher than that of placebo after multiple oral administrations. DWP14012 showed rapid and sustained suppression of gastric acid secretion for 24 hours after dosing. Clear dose‐response and exposure‐response relationships were observed. Plasma concentrations of DWP14012 increased in a dose‐proportional manner in the MAD study, whereas in the SAD study, DWP14012 did not significantly accumulate in the plasma.

Conclusions

DWP14012 was well tolerated, and showed a rapid and long‐lasting gastric acid suppression effect in healthy subjects. These results justify further investigation of DWP14012 in patients with acid‐related disorders.
Symptom relief and anejaculation after aquablation or transurethral resection of the prostate: subgroup analysis from a blinded randomized trial
Authors: Plante Mark , Gilling Peter , Barber Neil , Bidair Mohamed , Anderson Paul , Sutton Mark , Aho Tev , Kramolowsky Eugene , Thomas Andrew , Cowan Barrett , Kaufman Ronald P. , Trainer Andrew , Arther Andrew , Badlani Gopal , Desai Mihir , Doumanian Leo , Te Alexis E. , DeGuenther Mark , Roehrborn Claus
Published: June 2018

Objective

To test the hypothesis that benign prostatic hyperplasia (BPH) robotic surgery with aquablation would have a more pronounced benefit in certain patient subgroups, such as men with more challenging anatomies (e.g. large prostates, large middle lobes) and men with moderate BPH.

Methods

We conducted prespecified and post hoc exploratory subgroup analyses from a double‐blind, multicentre prospective randomized controlled trial that compared transurethral resection of the prostate (TURP) using either standard electrocautery vs surgery using robotic waterjet (aquablation) to determine whether certain baseline factors predicted more marked responses after aquablation as compared with TURP. The primary efficacy endpoint was reduction in International Prostate Symptom Score (IPSS) at 6 months. The primary safety endpoint was the occurrence of Clavien–Dindo persistent grade 1 or grade ≥2 surgical complications.

Results

For men with larger prostates (50–80 g), the mean IPSS reduction was four points greater after aquablation than after TURP (P = 0.001), a larger difference than the overall result (1.8 points; P = 0.135). Similarly, the primary safety endpoint difference (20% vs 46% [26% difference]; P = 0.008) was greater for men with large prostate compared with the overall result (26% vs 42% [16% difference]; P = 0.015). Postoperative anejaculation was also less common after aquablation compared with TURP in sexually active men with large prostates (2% vs 41%; P < 0.001) vs the overall results (10% vs 36%; P < 0.001). Exploratory analysis showed larger IPSS changes after aquablation in men with enlarged middle lobes, men with severe middle lobe obstruction, men with a low baseline maximum urinary flow rate, and men with elevated (>100) post‐void residual urine volume.

Conclusions

In men with moderate‐to‐severe lower urinary tract symptoms attributable to BPH and larger, more complex prostates, aquablation was associated with both superior symptom score improvements and a superior safety profile, with a significantly lower rate of postoperative anejaculation. The standardized, robotically executed, surgical approach with aquablation may overcome the increased outcome variability in more complex anatomy, resulting in superior symptom score reduction.
Children's Developing Descriptions and Judgments of Pretending
Authors: Sobel David M. , Letourneau Susan M.
Published: June 2018

Two studies investigated 4‐ to 7‐year‐olds’ knowledge about pretending. In Study 1, children (N = 66) defined pretending and described examples of own and others’ pretending. In Study 2, children (N = 52) defined pretending and then completed a battery of measures that examined their understanding that pretending involved mental states. In Study 1, older children articulated more defining features of pretending than younger children. When describing how they or others pretended, children focused on action or appearance, regardless of whether they had included more defining features in their definitions of pretending. In Study 2, the more defining features children articulated, the better their performance on the battery. We discuss the implications of these data for the role of pretending in children's developing theory of mind.
Mitoxantrone treatment in a patient with multiple sclerosis and pattern III lesions
Authors: Grüter Thomas , Metz Imke , Gahlen Anna , Kneiphof Janina , Stork Lidia , Brück Wolfgang , Gold Ralf , Kleiter Ingo
Published: June 2018

Background

Brain biopsies of multiple sclerosis patients identified three intraindividually stable lesion patterns. Apart from beneficial effects of plasma exchange in patients with type II lesions, little is known about how multiple sclerosis lesion histology could guide therapeutic decisions.

Case presentation

Here, we report on a 53‐year‐old male patient with polysymptomatic cerebral syndrome as the first episode of multiple sclerosis. Brain biopsy showed an inflammatory demyelinating lesion with apoptotic oligodendrocytes and a loss of myelin‐associated glycoprotein, pathological features typical for pattern III lesions. High‐dose steroids and immunosuppressive treatment with mitoxantrone led to a substantial improvement of disability and long‐term clinical stability.

Conclusion

Mitoxantrone therapy along with steroid pulses could potentially be considered as a therapeutic option for pattern III lesions.
Cytological diagnosis of a testicular tumour in an infertile male which mimicked epididymitis
Authors: Priyaa V. , Gochhait D. , Devi D. , Devi S. , Siddaraju N. , Manikandan R.
Published: June 2018

This case highlights an important differential diagnosis for testicular swellings associated with infertility and showed typical cytoplasmic inclusions which are characteristic although not always present even on histopathology.
Alcohol use, aquatic injury, and unintentional drowning: A systematic literature review
Authors: Hamilton Kyra , Keech Jacob J. , Peden Amy E. , Hagger Martin S.
Published: June 2018

Issues

Drowning is a global public health issue, and there is a strong association between alcohol and risk of drowning. No previous systematic review known to date has identified factors associated with alcohol use and engagement in aquatic activities resulting in injury or drowning (fatal and non‐fatal).

Approach

Literature published from inception until 31 January 2017 was reviewed. Included articles were divided into three categories: (i) prevalence and/or risk factors for alcohol‐related fatal and non‐fatal drowning and aquatic injury, (ii) understanding alcohol use and aquatic activities, and (iii) prevention strategies. Methodological quality of studies was assessed using National Health and Medical Research Council (NHMRC) Level of Evidence and risk of bias was assessed using the Newcastle‐Ottawa Quality Assessment Scales.

Key Findings

In total, 74 studies were included (57 on prevalence and/or risk factors, 15 on understanding alcohol use, and two on prevention strategies). Prevalence rates for alcohol involvement in fatal and non‐fatal drowning varied greatly. Males, boating, not wearing lifejackets, and swimming alone (at night, and at locations without lifeguards) were risk factors for alcohol‐related drowning. No specific age groups were consistently identified as being at risk. Study quality was consistently low, and risk of bias was consistently high across studies. Only two studies evaluated prevention strategies.

Implications

There is a need for higher quality studies and behavioural basic and applied research to better understand and change this risky behaviour.

Conclusion

On average, 49.46% and 34.87% of fatal and non‐fatal drownings, respectively, involved alcohol, with large variations among studies observed.
Efficacy and safety of trelagliptin in combination with insulin therapy in Japanese patients with type 2 diabetes: Results from a randomized, Phase IV study
Authors: Kaku Kohei , Kuroda Shingo , Ishida Kazuyuki , Umeda Yuusuke
Published: June 2018

We aimed to explore the efficacy and safety of once‐weekly trelagliptin 100 mg as an add‐on therapy to insulin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control. Patients with haemoglobin A1c (HbA1c) 7.5% to 10.0% who were receiving 8 to 40 units of insulin per day were randomized to receive, with insulin, trelagliptin 100 mg (A/A, n = 116) or placebo (P/A, n = 124) for a 12‐week double‐blind (DB) phase, after which all received trelagliptin for a 40‐week open‐label phase. Primary endpoints were HbA1c change from baseline to the end of the DB phase and adverse events (AEs).

HbA1c significantly decreased in the A/A group vs the P/A group at the end of the DB phase (least square mean difference, −0.63% [95% CI, −0.83 to −0.44]: P < .0001). The frequency of treatment‐emergent AEs during the DB phase was 44.0% in the A/A group and 47.6% in the P/A group. No patient experienced severe hypoglycaemia during trelagliptin treatment. Once‐weekly trelagliptin 100 mg therapy with insulin demonstrated a significant reduction in HbA1c. Long‐term treatment was well‐tolerated, with no clinically significant hypoglycaemia, suggesting that trelagliptin with insulin is a meaningful treatment option in this patient population.
Glycaemic control in the diabetes and Lifestyle Cohort Twente: A cross‐sectional assessment of lifestyle and pharmacological management on Hba1c target achievement
Authors: Jalving Annis C. , Gant Christina M. , Binnenmars S. Heleen , Soedamah‐Muthu Sabita S. , Bakker Stephan J. L. , Navis Gerjan , Laverman Gozewijn D.
Published: June 2018

The majority of patients with type 2 diabetes do not reach target levels of glycated haemoglobin (HbA1c < 7%). We investigated the prevalence of HbA1c‐target achievement and opportunities afforded by lifestyle and pharmacological treatment to increase target achievement. We performed cross‐sectional analyses of baseline data from the Diabetes and Lifestyle Cohort Twente‐1 (DIALECT‐1). Patients were divided according to (1) HbA1c <53 and ≥53 mmol/mol (<7%) and (2) non‐insulin treatment and tertiles of daily insulin use. We found that 161 (36%) patients achieved the target HbA1c level. Patients with HbA1c ≥53 mmol/mol had a longer duration of diabetes (13 [8‐20] vs 9 [4‐14] years; P < .001) and more frequently were insulin‐users (76% vs 41%, P < .001). Patients in the highest tertile of insulin use had a higher body mass index than those in the lowest tertile (35.8 ± 5.5 vs 29.8 ± 5.5 kg/m2; P < .001). Achievement of target HbA1c is low in this type 2 diabetes population. High resistance to pharmacological treatment, paralleled with high body mass index, illustrates that increasing insulin sensitivity through lifestyle intervention is the best opportunity to improve HbA1c target achievement in this real‐life population.
Index insurance and climate risk management: Addressing social equity
Authors: Fisher Eleanor , Hellin Jon , Greatrex Helen , Jensen Nathaniel
Published: June 2018

Fair distribution of benefits from index insurance matters. Lack of attention to social equity can reinforce inequalities and undermine the potential index insurance holds as a tool for climate risk management that is also pro‐poor. The aims of this article are to: (a) examine social equity concerns raised by index insurance in the context of climate risk management, (b) consider how greater attention can be paid to social equity in index insurance initiatives, and (c) reflect on the policy challenges raised by taking social equity into account as a mechanism for climate risk reduction. The article draws on learning from the CGIAR's Research Program on Climate Change, Agriculture and Food Security (CCAFS) and presents the cases of the Index Based Livelihoods Insurance (IBLI) and Agriculture and Climate Risk Enterprise Ltd. (ACRE) in East Africa. It proposes a framework for unpacking social equity related to equitable access, procedures, representation and distribution within index insurance schemes. The framework facilitates identification of opportunities for building outcomes that are more equitable, with greater potential for inclusion and fairer distribution of benefits related to index insurance. The article argues that systematically addressing social equity raises hard policy choices for index insurance initiatives without straightforward solutions. Attention to how benefits and burdens of index insurance are distributed, suggests the unpalatable truth for development policy that the poorest members of rural society can be excluded. Nevertheless, a focus on social equity—facilitated by the framework—opens up opportunities to ensure index insurance is linked to more socially just climate risk management. At the very least, it may prevent index insurance from generating greater inequality. Taking social equity into account, thus, shifts the focus from agricultural systems in transition per se to systems with potential to incorporate societal transformation through distributive justice.
Off‐label use of 4‐factor prothrombin complex concentrate is common despite little known benefit: A retrospective study
Authors: Scharman Carlton D. , Shatzel Joseph J. , Kim Edward , DeLoughery Thomas G.
Published: June 2018

Background/Objective

While four‐factor prothrombin complex concentrate (4F‐PCC) is FDA‐approved for reversal of warfarin‐induced major bleeding, its use in real‐world settings is unclear. This study's objective was to identify indications leading to 4F‐PCC use and associated outcomes at a single university hospital.

Methods

This was a retrospective cohort study of patients receiving 4F‐PCC over a 22‐month period. A dose was “on‐label” if given for reversal of warfarin‐induced coagulopathy in patients with major bleeding or requiring urgent surgeries/procedures; other doses were “off‐label”.

Results

A total of 165 doses of 4F‐PCC in 154 patients were given. Sixty‐one percent of doses were on‐label, while 39% were off‐label. Intracranial hemorrhage was the most common indication (55% of doses). On‐label patients had significantly higher rate of INR normalization and survival to hospital discharge than off‐label patients. There was no difference in time to INR normalization, time to hemostasis, or incidence of thromboembolic complications.

Conclusions

Off‐label use of 4F‐PCC is likely common, occurring in nearly 40% of drug administrations at our center. Larger‐scale prospective trials studying specific indications are needed for validation in off‐label settings. Until such evidence is available, given potential harms historically displayed by off‐label use of other hemostatic agents, limiting off‐label 4F‐PCC use is recommended.
Experimenting in the Unknown: Lessons from The Manhattan Project
Authors: Gillier Thomas , Lenfle Sylvain
Published: June 2018

Experimentation is paramount to innovation. In fact, innovation scholars and practitioners have espoused Thomke's (2003) book titled Experimentation matters: Unlocking the potential of new technologies for innovation. Unfortunately, companies still experience considerable technical and managerial difficulties with organizing experiments under high uncertainty. This study confronts Thomke's experimentation principles with a high uncertainty context by examining experiments conducted by The Manhattan Project from 1943–1945, the initiative that created the first implosion‐type fission bomb. Findings suggest that lack of theoretical knowledge, a crisis of scientific instruments, and absence of pre‐established organizations were critical to such highly uncertain experimentation. We conclude with a discussion of the boundary conditions of Thomke's experimentation principles. Finally, we propose five principles for facilitating the management of experimentation in the unknown.
Role of PPAR‐α agonist fenofibrate in the treatment of induced benign prostatic hyperplasia with dysplastic changes in rats
Authors: Refaie Marwa M.M. , Rifaai Rehab A. , Zenhom Nagwa M.
Published: June 2018

Nearly all men who reach average life expectancy have prostate disease. The most common is benign prostatic hyperplasia (BPH). Peroxisome proliferator‐activated receptor alpha (PPARα) had protective effect in different models, but still, there are no studies explain its role in BPH. So that we investigated the effect of fenofibrate (FEN) on induced BPH by testosterone propionate (TP) (3 mg/kg/day for 4 weeks) subcutaneous injection followed by FEN (300 mg/kg/day) was given orally for 4 weeks. We measured prostate weights changes, prostatic tissue superoxide dismutase (SOD), and malondialdehyde (MDA) levels. Prostate‐specific antigen (PSA), dihydrotestosterone (DHT), and total antioxidant capacity (TAC) in serum were determined. The mRNA gene expressions of proliferating cell nuclear antigen (PCNA), PPARα, and glutathione peroxidase (GPx) in prostatic tissue were also measured by quantitative real‐time polymerase chain reaction. In addition, the histopathological changes and activated caspase3 immunoexpression were evaluated. Our results showed that TP succeeded in induction of BPH, which was detected by significant increase in prostate weights, prostatic tissue MDA, serum levels of DHT, PSA, and mRNA gene expression of PCNA but significant decrease in PPARα and GPx gene expression. Moreover, TAC in serum and SOD level in prostate tissue decreased. The histopathological examination showed typical changes of BPH with dysplastic changes with marked decrease in activated caspase3 immunoexpression indicating marked suppression of the apoptotic process. FEN significantly improved all disturbed parameters of BPH model. Moreover, there are no dysplastic changes with co‐administration of FEN to BPH induced group.
Evaluation of pan‐TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis‐like neural tumour and histological mimics
Authors: Hung Yin P , Fletcher Christopher D M , Hornick Jason L
Published: June 2018

Aims

Infantile fibrosarcoma is characterised by intersecting fascicles of spindle cells and ETV6–NTRK3 gene fusion in most cases. Given histological overlap with other spindle‐cell tumours, the diagnosis can be challenging and often requires molecular confirmation. A recently developed pan‐TRK antibody shows promise for identifying tumours with NTRK fusions. The purpose of this study was to evaluate the potential diagnostic utility of pan‐TRK immunohistochemistry for infantile fibrosarcoma.

Methods and results

We evaluated whole‐tissue sections from 210 cases, including 15 infantile fibrosarcomas; five each lipofibromatosis‐like neural tumour and lipofibromatosis; 10 each primitive myxoid mesenchymal tumour of infancy (PMMTI) and low‐grade myofibroblastic sarcoma; 15 each fibrous hamartoma of infancy (FHI), myofibroma/myofibromatosis and desmoid‐type fibromatosis; and 20 each low‐grade fibromyxoid sarcoma, synovial sarcoma, spindle‐cell rhabdomyosarcoma, malignant peripheral nerve sheath tumour, fibrosarcomatous dermatofibrosarcoma protuberans (F‐DFSP) and nodular fasciitis. Immunohistochemistry was performed using a rabbit monoclonal pan‐TRK antibody. Immunoreactivity for pan‐TRK was observed in all 15 (100%) infantile fibrosarcomas, including diffuse immunoreactivity (>50% of cells) in 14 (93%) cases. Pan‐TRK was positive in all five (100%) lipofibromatosis‐like neural tumours. Of the 190 histological mimics, diffuse pan‐TRK immunoreactivity was noted in 16 (8%) cases, including five PMMTI, five FHI (highlighting predominantly the primitive myxoid spindle‐cell components), three F‐DFSP, one low‐grade myofibroblastic sarcoma, one myofibroma and one spindle‐cell rhabdomyosarcoma.

Conclusions

Diffuse pan‐TRK immunoreactivity is a highly sensitive but not entirely specific diagnostic marker for infantile fibrosarcoma, and may be helpful in selecting patients for TRK‐targeted therapy. As expected, lipofibromatosis‐like neural tumours, which harbour NTRK1 fusions, also show diffuse pan‐TRK immunoreactivity.
Survival in HIV‐infected patients with lymphoma according to the choice of antiretroviral treatment: an observational multicentre study
Authors: Focà E , Cavaglià G , Rusconi S , Cascavilla A , Cenderello G , Re A , Casari S , van den Bogaart L , Zinzani PL , Caracciolo D , Di Perri G , Bonito A , Lucchini A , Cassola G , Viale P , Calcagno A
Published: June 2018

Objectives

Lymphoproliferative disorders are often observed in HIV‐positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge.

Methods

A retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV‐positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival.

Results

A total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B‐cell lymphoma (DLCLB; n = 164), Hodgkin lymphoma (HL; n = 99) and Burkitt lymphoma (BL; n = 57), followed by plasmablastic lymphoma (PBL; n = 38), T‐cell lymphoma (TCL; n = 17), indolent lymphoma (n = 10) and other less common types (n = 14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)‐based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based and in 18 it was integrase strand transfer inhibitor (INSTI)‐based (the remaining 20 individuals received other regimens). The 5‐year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI‐based ART compared with other compounds was associated with worse survival in non‐Hodgkin lymphoma (NHL) and HL patients combined (P ≤ 0.001) and in NHL patients alone (P < 0.001); grade 3–4 haematological toxicities were more commonly observed in PI‐treated individuals. Lymphoma diagnosis in recent years, better immunovirological status, lower lymphoma stage and better prognostic indexes were associated with better survival.

Conclusions

PI‐based cART while on chemotherapy was associated with worse overall survival and more frequent haematological complications in HIV‐positive patients with lymphoma.
Insights into the phenolic compounds present in jambolan (Syzygium cumini) along with their health‐promoting effects
Authors: Singh Balwinder , Singh Jatinder Pal , Kaur Amritpal , Singh Narpinder
Published: June 2018

Jambolan is a rich source of bioactive phenolic compounds that have many potential health benefits. Phenolic acids, flavonoids (mainly anthocyanins, flavonols, flavanols and flavanonols) and tannins are the major phenolic compounds present in different parts of jambolan plant. Jambolan fruit skin mainly contains anthocyanins (such as delphinidin, petunidin, malvidin in glycosylated forms), while the pulp is primarily rich in phenolic acids (such as gallic acid and ellagic acid) and tannins (mostly ellagitannins). Moreover, many other compounds have been reported to be present in jambolan fruit. Apart from fruit skin and pulp, jambolan leaves contain flavonoids such as quercetin, myricetin and flavonol glycosides, while seeds are known to contain ellagic acid, gallic acid and quercetin. Health‐promoting activities of phenolic compounds present in jambolan reported in the literature are functioning as anti‐inflammatory, anti‐allergic, antihyperglycaemic, anticancer, cardioprotective, radioprotective, antibacterial, chemopreventive and antioxidant agents.
Skin cancers and dermal substitutes: Is it safe? Review of the literature and presentation of a 2‐stage surgical protocol for the treatment of non‐melanoma skin cancers of the head in fragile patients
Authors: Marcasciano Marco , Mazzocchi Marco , Kaciulyte Juste , Spissu Noemi , Casella Donato , Ribuffo Diego , Dessy Luca Andrea
Published: June 2018

Non‐melanoma skin cancers (NMSC) represent the most common skin tumours of the head region. We describe the use of dermal substitute in a 2‐stage surgery protocol for selected fragile patients to remove NMSC of the head region. A review of the literature focusing on dermal substitutes’ safety after skin tumours excision is provided. A total of 45 fragile patients with NMSC in the head region were selected and scheduled for the 2‐stage surgical protocol. The first stage consisted of traditional surgical excision and immediate coverage with Hyalomatrix (Fidia Advanced Biopolymers, Abano Terme, Italy). After histology confirmed diagnosis and clearance of the margins, full‐thickness skin autografts were performed. All of the patients reached complete tumour excision and wound healing. No local recurrences were registered during 24 months follow up. The 2‐stage surgical therapeutic‐diagnostic‐reconstructive approach represents a less stressful and oncologically safe surgical protocol in selected fragile patients. When patients cannot tolerate invasive and long surgical procedures, general anaesthesia, and long hospitalisation, skin grafting following temporary skin substitute coverage can achieve oncological clearance and provide good functional and aesthetic results. The use of dermal substitutes represents a valid alternative surgical option in cases of ASA III, fragile patients non‐eligible for complex reconstructive surgery. To our knowledge, this is the first paper reviewing literature focusing on dermal substitutes’ applications and safety after skin tumour excision.
Role of anaerobes in polymicrobial communities and biofilms complicating diabetic foot ulcers
Authors: Percival Steven L , Malone Matthew , Mayer Dieter , Salisbury Anne‐Marie , Schultz Gregory
Published: June 2018

Infected tissues in the feet of people with diabetes in the form of a diabetic foot ulcer (DFU) present a complex pathology for clinicians to manage. This is partly attributed to the multi‐factorial nature of the disease, which may include; altered foot architecture leading to excessive plantar pressures and frictional forces peripheral arterial disease and loss of protective sensation. In addition, to the above co‐morbid variables, it is understood that a delayed wound healing state may be perpetuated by the presence of microorganisms residing in the wound tissue. The microbiology of chronic DFUs has often been reported as being polymicrobial. Of growing interest is the presence and potential role of anaerobic microorganisms in the pathology of DFUs and how they may contribute to the infective process or delayed healing. The presence of anaerobes in DFUs has been greatly underestimated, largely due to the limitations of conventional culture methods in identifying them from samples. Advancements in molecular and microscopy techniques have extended our view of the wound microbiome in addition to observing the growth and behaviour (planktonic or biofilm) of microorganisms in situ. This review paper will reflect on the evidence for the role and significance of anaerobes in DFUs and infection. A focus of this review will be to explore recent advancements in molecular genomics and microscopy techniques in order to better assess the roles of anaerobic bacteria in chronic DFUs and in biofilm‐based wound care.
Reproductive management of the Orinoco river dolphin Inia geoffrensis humboldtiana in Venezuela
Authors: Boede E. O. , Mujica‐Jorquera E. , Boede F. , Varela C.
Published: June 2018

The Orinoco river dolphin Inia geoffrensis humboldtiana is included in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora. The International Union for Conservation of Nature Red List used to categorize the Orinoco river dolphin as Vulnerable; however, it is now considered Data Deficient because current information about threats, ecology and the population are limited and out of date. The Red Book of Venezuelan Wildlife categorizes the species as ‘vulnerable’, and the Venezuelan National Biodiversity Strategy and Action Plan identifies ex situ conservation actions for threatened species. The distribution of this river dolphin in Venezuela extends from the Casiquiare canal, upper/mid‐/lower Orinoco River, tributaries, through the delta, where its populations are threatened by the deterioration of habitat, illegal hunting and accidental capture in fishing nets. Captive‐breeding programmes for cetacean river species worldwide, including the Orinoco river dolphin, have led to an increase in knowledge about reproductive parameters and biological data, which is helpful for future conservation planning. Detailed husbandry manuals and management procedures, which were insufficient at the time the data were collected, are of vital importance for the sustained survival and reproduction of this species ex situ, especially if the conservation status should change from Vulnerable to Critically Endangered. Valencia Aquarium, Venezuela, housed Orinoco river dolphins for 41 years, from 1975 onwards. In 1994 a reproductive group was established with one male and two females. Over the next 22 years (1994–2016) eight calves were born. The following report details the prenatal management, birthing events, lactation periods, and sizes, weights and survival of the young.
Restitution Post Bellum: Property, Inheritance, and Corrective Justice
Authors: Butt Daniel
Published: June 2018

When should property which was unjustly taken in wartime be returned to the victims of misappropriation, or their heirs? This article argues that Cécile Fabre's Cosmopolitan Peace understates the force of arguments favouring restitution. Rather than seeing claims for restitution made by the descendants of victims as concerned with the redress of harm, they can be understood as resting on enduring entitlements to property. This allows for an account of corrective justice which is robust across generations, and which can be justified aside from, and even sometimes in opposition to, concerns of distributive justice.