bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of time to primary repair on final visual outcome after open globe injury
Authors: Blanch Richard J , Bishop Jonathan , Javidi Hedayat , Murray Philip Ian 
Published: January 2019

Background/AimHistoric data suggest that open globe injuries should be repaired within 12–24 hours to reduce the risk of endophthalmitis. However, endophthalmitis is uncommon when systemic antibiotic prophylaxis is given. It is not clear whether delayed primary repair impacts visual outcomes in other ways or what is the optimum time to repair. We aimed to examine the effect of time to primary repair on visual outcomes.MethodsThis is a retrospective comparative case series including all open globe injuries presenting to the Birmingham Midland Eye Centre between 1 January 2014 and 15 March 2016. Presenting features, mechanism of injury, visual acuity at 6–12 months and demographic data were examined.Results56 open globe injuries were repaired, of which sufficient data for analysis were available on 52 cases. The mean time to primary repair was 1 day after injury (range 5 hours to 7 days). Final visual acuity at 6–12 months was related to the presenting visual acuity and the Ocular Trauma Score and to the time between injury and primary repair, with a reduction in predicted visual acuity of logarithm of the minimum angle of resolution of 0.37 for every 24 hours of delay (95% CI 0.14 to 0.6).DiscussionOpen globe injuries should be repaired promptly. Presenting visual acuity remains the strongest predictor of outcome; however, delay to primary repair also reduced final visual acuity, and any significant delay from injury to repair is likely to negatively impact final visual outcome.
Classifying signs and symptoms of dry eye disease according to underlying mechanism via the Delphi method: the DIDACTIC study
Authors: Labetoulle Marc , Bourcier Tristan , Doan Serge 
Published: January 2019

Background/aimsDry eye disease (DED) is categorised by pathophysiology as aqueous deficient dry eye (ADDE), evaporative dry eye (EDE) or mixed. Treatment should be tailored to DED pathophysiology, but this is challenging to determine. This Delphi consultation aimed to categorise and weight signs and symptoms to help identify the evaporative or aqueous deficient DED origin.MethodsA panel of French DED experts created an initial list of 77 DED signs and symptoms. In a Delphi consultation, experts categorised items by DED pathophysiology. Likert scoring was used to indicate whether items were strongly or moderately indicative of ADDE or EDE. Items could also be judged non-applicable to DED, with the opportunity to suggest alternative diagnoses.ResultsExperts attributed 19 items (of which 11 were strongly indicative) to a pathophysiology of EDE and 12 items (of which four were strongly indicative) to ADDE. Items scored strongly indicative with agreement >90% for EDE were previous chalazia, rosacea/rhinophyma, telangiectasias of eyelid margin and thick non-expressible meibomian gland secretions, and for ADDE were Sjögren syndrome or associated disease, and Schirmer <5 mm after 5 min (without anaesthesia). Seventeen items indicated neither pathophysiology and 18 items were found to be suggestive of alternative diagnoses.ConclusionsThis Delphi consultation categorised signs and symptoms, using an innovative weighting system to identify DED pathophysiology. An algorithm integrating the weighting of each sign and symptom of an individual patient would be valuable to help general ophthalmologists to classify the DED subtype and tailor treatment to DED underlying mechanism.
Healthcare professionals’ moral distress in adult palliative care: a systematic review
Authors: Maffoni Marina , Argentero Piergiorgio , Giorgi Ines , Hynes Julia , Giardini Anna 
Published: January 2019

ObjectivesPalliative care providers may be exposed to numerous detrimental psychological and existential challenges. Ethical issues in the healthcare arena are subject to continual debate, being fuelled with ongoing medical, technological and legal advancements. This work aims to systematically review studies addressing the moral distress experienced by healthcare professionals who provide adult palliative care.MethodsA literature search was performed on PubMed, Scopus, Web of Science and PsycINFO databases, searching for the terms ‘moral distress’ AND ‘palliative care’. The review process has followed the international PRISMA statement guidelines.ResultsThe initial search identified 248 papers and 10 of them were considered eligible. Four main areas were identified: (1) personal factors, (2) patients and caregivers, (3) colleagues and superiors and (4) environment and organisation. Managing emotions of self and others, witnessing sufferance and disability, caring for highly demanding patients and caregivers, as well as poor communication were identified as distressing. Moreover, the relationship with colleagues and superiors, and organisational constraints often led to actions which contravened personal values invoking moral distress. The authors also summarised some supportive and preventive recommendations including self-empowerment, communication improvement, management of emotions and specific educational programmes for palliative care providers. A holistic model of moral distress in adult palliative care (integrating emotional, cognitive, behavioural and organisational factors) was also proposed.ConclusionsCognisance of risk and protective factors associated with the moral distress phenomenon may help reframe palliative healthcare systems, enabling effective and tailored actions that safeguard the well-being of providers, and consequently enhance patient care.
Heart or heart-lung transplantation for patients with congenital heart disease in England
Authors: Dimopoulos Konstantinos , Muthiah Kavitha , Alonso-Gonzalez Rafael , Banner Nicholas Robert , Wort Stephen J , Swan Lorna , Constantine Andrew Harry , Gatzoulis Michael A , Diller Gerhard Paul , Kempny Aleksander 
Published: January 2019

BackgroundIncreased longevity in patients with congenital heart disease (CHD) is associated with late complications, mainly heart failure, which may not be amenable to redo surgery and become refractory to medical therapy and so, trigger referral for transplantation. We assessed the current role and future prospects of heart and heart-lung transplantation for patients with CHD in England.MethodsWe performed a retrospective analysis of hospital episodes for England for 1997–2015, identifying patients with a CHD code (ICD-10 ‘Q2xx.x’), who underwent heart or heart-lung transplantation.ResultsIn total, 469 transplants (82.2% heart and 17.8% heart-lung) were performed in 444 patients. Half of patients transplanted had mild or moderate CHD complexity, this percentage increased with time (p=0.001). While overall, more transplantations were performed over the years, the proportion of heart-lung transplants declined (p<0.0001), whereas the proportion of transplants performed in adults remained static. Mortality was high during the first year, especially after heart-lung transplantation, but remained relatively low thereafter. Older age and heart-lung transplantation were strong predictors of death. While an increase in CHD transplants is anticipated, actual numbers in England seem to lag behind the increase in CHD patients with advanced heart failure.ConclusionsThe current and future predicted increase in the numbers of CHD transplants does not appear to parallel the expansion of the CHD population, especially in adults. Further investment and changes in policy should be made to enhance the number of donors and increase CHD transplant capacity to address the increasing numbers of potential CHD recipients and optimise transplantation outcomes in this growing population.
Implications of uninterrupted preoperative transdermal buprenorphine use on postoperative pain management
Authors: Martin Yvette N , Pearson Amy C S , Tranchida John R , Weingarten Toby N , Schulte Phillip J , Sprung Juraj 
Published: January 2019

Background and objectivesBuprenorphine is a partial µ-receptor agonist resistant to displacement from receptors by conventional opioids, which can block the effect of conventional opioids and may interfere with postoperative pain management. We aimed to quantify perioperative opioid use in patients receiving transdermal buprenorphine (TdBUP).MethodsWe identified patients receiving TdBUP who underwent surgery between 2004 and 2016. To compare opioid requirements (intravenous morphine equivalents (IV-MEq)), we constructed a matched study, matching each TdBUP patient with two opioid-naive patients by sex, age, and type of anesthesia and procedure.ResultsNineteen unique patients underwent 22 procedures while receiving TdBUP. Total (IQR) amounts of IV-MEq (intraoperative, recovery room, and 24 hours after recovery-room discharge) were 98 (63, 145) and 46 (30, 65) mg IV-MEq for TdBUP and opioid-naive patients, respectively (p<0.001). Postoperative IV-MEq requirements were 54 (38, 90) and 15 (3, 35) mg for TdBUP and opioid-naive patients, respectively (p<0.001). Among TdBUP patients, higher preoperative doses of TdBUP were associated with greater postoperative opioid requirements (p=0.02). Specifically, patients with a 20 µg/hour TdBUP patch required 133.8 mg IV-MEq more postoperatively than patients with a 5 µg/hour patch (p=0.002). Following discharge from the recovery room, 17 (77%) TdBUP patients and 15 (34%) opioid-naive patients reported severe pain (OR 6.6 (95% CI 2.0 to 21.3); p<0.001; adjusting for baseline pain score, 5.0 (95% CI, 1.4 to 17.8); p=0.01).ConclusionsAnalgesic management for patients receiving TdBUP therapy must account for increased opioid needs, and greater preoperative doses of TdBUP were associated with greater postoperative opioid requirements.
Salivary gland secretome: a novel tool towards molecular stratification of patients with primary Sjögren’s syndrome and non-autoimmune sicca
Authors: Blokland Sofie L M , Hillen Maarten R , van Vliet-Moret Fréderique M , Bikker Angela , de Jager Wilco , Pandit Aridaman , Kruize Aike A , Radstake Timothy R D J , van Roon Joel A G 
Published: January 2019

ObjectiveTo explore the potential of salivary gland biopsy supernatants (the secretome) as a novel tool to aid in stratification of patients with sicca syndrome and to study local immunopathology in Sjögren’s syndrome.MethodsLabial salivary gland biopsies were incubated in saline for 1 hour. In these tissue supernatants from a discovery cohort (n=16) of patients with primary Sjögren’s syndrome (pSS) and non-Sjögren’s sicca (nSS), 101 inflammatory mediators were measured by Luminex. Results were validated in a replication cohort (n=57) encompassing patients with pSS, incomplete SS and nSS.ResultsThe levels of 23 cytokines were significantly increased in patients with pSS versus nSS in the discovery cohort. These 23 and 3 additional cytokines were measured in a second cohort. Elevated concentrations of 11 cytokines were validated and the majority correlated with clinical parameters. Classification tree analysis indicated that the concentrations of CXCL13, IL-21, sIL-2R and sIL-7Rα could be used to classify 95.8% of patients with pSS correctly.ConclusionLabial salivary gland secretomes can be used to reliably assess mediators involved in immunopathology of patients with pSS, potentially contributing to patient classification. As such, this method represents a novel tool to identify therapeutic targets and markers for diagnosis, prognosis and treatment response.
Tofacitinib or adalimumab versus placebo: patient-reported outcomes from OPAL Broaden—a phase III study of active psoriatic arthritis in patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs
Authors: Strand Vibeke , de Vlam Kurt , Covarrubias-Cobos Jose A , Mease Philip J , Gladman Dafna D , Graham Daniela , Wang Cunshan , Cappelleri Joseph C , Hendrikx Thijs , Hsu Ming-Ann 
Published: January 2019

ObjectivesTofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). We evaluated patient-reported outcomes (PROs) in patients with PsA refractory to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and tumour necrosis factor inhibitor-naïve in a 12-month, phase III randomised controlled trial (OPAL Broaden [NCT01877668]).MethodsPatients (N=422) received tofacitinib 5 mg or 10 mg twice daily, adalimumab 40 mg subcutaneously every 2 weeks or placebo advancing to tofacitinib 5 mg or 10 mg twice daily at month 3. Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences (MCID); and scores ≥normative values in: Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level questionnaire (EQ-5D-3L) and Ankylosing Spondylitis Quality of Life (ASQoL) were determined. Nominal p values were cited without multiple comparison adjustments.ResultsAt month 3, PtGA, Pain, PGJS, FACIT-Fatigue, EQ-5D-3L, ASQoL and SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP) and vitality domain scores exceeded placebo with both tofacitinib doses (p≤0.05); SF-36v2 social functioning with 5 mg twice daily (p≤0.05). Percentages reporting improvements ≥MCID in PtGA, Pain, PGJS, FACIT-Fatigue, ASQoL and SF-36v2 PCS, PF, BP and general health scores exceeded placebo with both tofacitinib doses (p≤0.05) and were similar with adalimumab.ConclusioncsDMARD-IR patients with active PsA reported statistically and clinically meaningful improvements in PROs with tofacitinib compared with placebo at Month 3.
Effect of tofacitinib on patient-reported outcomes in patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors in the phase III, randomised controlled trial: OPAL Beyond
Authors: Strand Vibeke , de Vlam Kurt , Covarrubias-Cobos Jose A , Mease Philip J , Gladman Dafna D , Chen Linda , Kudlacz Elizabeth , Wu Joseph , Cappelleri Joseph C , Hendrikx Thijs , Hsu Ming-Ann 
Published: January 2019

ObjectivesTofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). Patient-reported outcomes (PROs) were evaluated in patients with PsA with inadequate responses to tumour necrosis factor inhibitors (TNFi-IR) in a 6-month, phase III randomised controlled trial (OPAL Beyond [NCT01882439]).MethodsPatients (N=394) received tofacitinib 5 or 10 mg twice daily or placebo (advancing to tofacitinib 5 or 10 mg twice daily at month 3). Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences and scores ≥normative values were determined in Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level (EQ-5D-3L), EQ-VAS and Ankylosing Spondylitis Quality of Life (ASQoL). Nominal p values are without multiple comparison adjustments.ResultsAt month 3, PtGA, Pain, PGJS, SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP), vitality and social functioning (SF) domains, FACIT-Fatigue Total score, EQ-5D-3L pain/discomfort, EQ-VAS and ASQoL scores exceeded placebo with both tofacitinib doses (role physical [RP] with 10 mg twice daily only; p≤0.05). Patients reporting improvements ≥MCID (%) in PtGA, PGJS, Pain, ASQoL and SF-36v2 PCS, PF, RP, BP, SF (both tofacitinib doses) exceeded placebo (p≤0.05).ConclusionTNFi-IR patients with PsA receiving tofacitinib reported statistically and clinically meaningful improvements in PROs versus placebo over 3 months, which were maintained to month 6. Despite lower baseline scores, these improvements were similar to the csDMARD-IR TNFi-naive OPAL Broaden trial.
Circulating Biomarkers Predicting Longitudinal Changes in Left Ventricular Structure and Function in a General Population
Authors: Cauwenberghs Nicholas , Ravassa Susana , Thijs Lutgarde , Haddad Francois , Yang Wen‐Yi , Wei Fang‐Fei , López Begoña , González Arantxa , Díez Javier , Staessen Jan A. , Kuznetsova Tatiana 
Published: January 2019

Background

Serial imaging studies in the general population remain important to evaluate the usefulness of pathophysiologically relevant biomarkers in predicting progression of left ventricular (LV) remodeling and dysfunction. Here, we assessed in a general population whether these circulating biomarkers at baseline predict longitudinal changes in
LV
structure and function.

Methods and Results

In 592 participants (mean age, 50.8 years; 51.4% women; 40.5% hypertensive), we derived echocardiographic indexes reflecting
LV
structure and function at baseline and after 4.7 years. At baseline, we measured alkaline phosphatase, markers of collagen turnover (procollagen type I, C‐terminal telopeptide, matrix metalloproteinase‐1) and high‐sensitivity cardiac troponin T. We regressed longitudinal changes in
LV
indexes on baseline biomarker levels and reported standardized effect sizes as a fraction of the standard deviation of
LV
change. After full adjustment, a decline in
LV
longitudinal strain (−14.2%) and increase in E/e′ ratio over time (+18.9%;
P
≤0.019) was associated with higher alkaline phosphatase activity at baseline. Furthermore, longitudinal strain decreased with higher levels of collagen I production and degradation at baseline (procollagen type I, −14.2%; C‐terminal telopeptide, −16.4%;
P
≤0.029). An increase in E/e′ ratio over time was borderline associated with lower matrix metalloproteinase‐1 (+9.8%) and lower matrix metalloproteinase‐1/tissue inhibitor of metalloproteinase‐1 ratio (+11.9%;
P
≤0.041). Higher high‐sensitivity cardiac troponin T levels at baseline correlated significantly with an increase in relative wall thickness (+23.1%) and
LV
mass index (+18.3%) during follow‐up (
P
≤0.035).

Conclusions

We identified a set of biomarkers predicting adverse changes in
LV
structure and function over time. Circulating biomarkers reflecting
LV
stiffness, injury, and collagen composition might improve the identification of subjects at risk for subclinical cardiac maladaptation.
Increased Expression of MicroRNA‐206 Inhibits Potassium Voltage‐Gated Channel Subfamily A Member 5 in Pulmonary Arterial Smooth Muscle Cells and Is Related to Exaggerated Pulmonary Artery Hypertension Following Intrauterine Growth Retardation in Rats
Authors: Lv Ying , Fu Linchen , Zhang Ziming , Gu Weizhong , Luo Xiaofei , Zhong Ying , Xu Shanshan , Wang Yu , Yan Lingling , Li Min , Du Lizhong 
Published: January 2019

Background

Intrauterine growth retardation (
IUGR
) is related to pulmonary artery hypertension in adults, and mi
croRNA
‐206 (miR‐206) is proposed to affect the proliferation and apoptosis of pulmonary artery smooth muscle cells (
PASMC
s) via post‐transcriptional regulation.

Methods and Results

In an
IUGR
rat model, we found that the expression and function of potassium voltage‐gated channel subfamily A member 5 (Kv1.5) in
PASMC
s was inhibited, and pulmonary artery hypertension was exaggerated after chronic hypoxia (
CH
) treatment as adults. micro
RNA
expression was investigated in
PASMC
s from 12‐week‐old male
IUGR
rats with
CH
by microarray, polymerase chain reaction, and in situ hybridization. The expression levels of Kv1.5 in primary cultured
PASMC
s and pulmonary artery smooth muscle from
IUGR
or control rats were evaluated with and without application of an miR‐206 inhibitor. Right ventricular systolic pressure, cell proliferation, luciferase reporter assay, and

I
K

v
were also calculated. We found increased expression of miR‐206 in resistance pulmonary arteries of
IUGR
rats at 12 weeks compared with newborns. Application of an miR‐206 inhibitor in vivo or in vitro increased expression of Kv1.5 α‐protein and
KCNA
5. Also, decreased right ventricular systolic pressure and cell proliferation were observed in
PASMC
s from 12‐week‐old control and
IUGR
rats after
CH
, while inhibitor did not significantly affect control and
IUGR
rats.

Conclusions

These results suggest that expression of Kv1.5 and 4‐aminopyridine (Kv channel special inhibitor)‐sensitive Kv current were correlated with the inhibition of miR‐206 in
PA
rings of
IUGR
‐
CH
rats and cultured
IUGR PASMC
s exposed to hypoxia. Thus, miR‐206 may be a trigger for induction of exaggerated CH–pulmonary artery hypertension of
IUGR
via Kv1.5.
Association of Obstructive Sleep Apnea With Cardiovascular Outcomes in Patients With Acute Coronary Syndrome
Authors: Fan Jingyao , Wang Xiao , Ma Xinliang , Somers Virend K. , Nie Shaoping , Wei Yongxiang 
Published: January 2019

Background

The prognostic significance of obstructive sleep apnea (
OSA
) in patients with acute coronary syndrome (
ACS
) in the contemporary era is unclear. We performed a large, prospective cohort study and did a landmark analysis to delineate the association of
OSA
with subsequent cardiovascular events after
ACS
onset.

Methods and Results

Between June 2015 and May 2017, consecutive eligible patients admitted for
ACS
underwent cardiorespiratory polygraphy during hospitalization.
OSA
was defined as an apnea‐hypopnea index ≥15 events·h
−1
. The primary end point was major adverse cardiovascular and cerebrovascular event (
MACCE
), including cardiovascular death, myocardial infarction, stroke, ischemia‐driven revascularization, or hospitalization for unstable angina or heart failure.
OSA
was present in 403 of 804 (50.1%) patients. During median follow‐up of 1 year, cumulative incidence of
MACCE
was significantly higher in the
OSA
group than in the non‐
OSA
group (log‐rank,
P
=0.041). Multivariate analysis showed that
OSA
was nominally associated with incidence of
MACCE
(adjusted hazard ratio, 1.55; 95% CI, 0.94–2.57;
P
=0.085). In the landmark analysis, patients with
OSA
had 3.9 times the risk of incurring a
MACCE
after 1 year (adjusted hazard ratio, 3.87; 95% CI, 1.20–12.46;
P
=0.023), but no increased risk was found within 1‐year follow‐up (adjusted hazard ratio, 1.18; 95% CI, 0.67–2.09;
P
=0.575). No significant differences were found in the incidence of cardiovascular death, myocardial infarction, and ischemia‐driven revascularization, except for a higher rate of hospitalization for unstable angina in the
OSA
group than in the non‐
OSA
group (adjusted hazard ratio, 2.10; 95% CI, 1.09–4.05;
P
=0.027).

Conclusions

There was no independent correlation between
OSA
and 1‐year
MACCE
after
ACS
. The increased risk associated with
OSA
was only observed after 1‐year follow‐up. Efficacy of
OSA
treatment as secondary prevention after
ACS
requires further investigation.