bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Safety of Obstetric Acupuncture: Forbidden Points Revisited
Authors: Carr David John 
Published: September 2015

Background/Aim Although the safety of acupuncture per se in pregnancy is reasonably well accepted, there remains debate regarding needling at points historically considered to be ‘forbidden’ during pregnancy. This article reviews the scientific literature on this topic. Main Findings There is no objective evidence of harm following needling at forbidden points, summarised by the following four lines of evidence. (1) In 15 clinical trials (n=823 women receiving n=4549–7234 acupuncture treatments at one or more forbidden points) rates of preterm birth (PTB) and stillbirth following are equivalent to those in untreated control groups and consistent with background rates of these complications in the general population. (2) Observational studies, including a large cohort of 5885 pregnant women needled at forbidden points at all stage of pregnancy, demonstrate that rates of miscarriage, PTB, preterm prelabour rupture of membranes (PPROM), and preterm contractions (preterm labour (PTL) or threatened PTL) are comparable with untreated controls and/or consistent with their anticipated incidence. (3) There is no reliable evidence that acupuncture/electroacupuncture (EA) can induce miscarriage/labour, even under otherwise favourable circumstances such as post-dates pregnancy or intrauterine fetal death. (4) Laboratory experiments using pregnant rats have demonstrated that repeated EA at forbidden points throughout gestation does not influence rates of post-implantation embryonic demise or cause miscarriage, fetal loss or resorption. Conclusions These findings are reassuring and will help individualised risk:benefit assessment before treating pregnant women. Given the numerous evidence-based indications for obstetric acupuncture and lack of evidence of harm, risk:benefit assessments will often fall in favour of treatment.
External validity of a randomised controlled trial on the treatment of severe infections caused by MRSA
Authors: Paul Mical , Bronstein Ella , Yahav Dafna , Goldberg Elad , Bishara Jihad , Leibovici Leonard 
Published: September 2015

ObjectivesTo assess the external validity of a pragmatic, investigator-initiated RCT on treatment of severe infections caused by methicillin-resistantStaphylococcus aureus(MRSA), we compared patient characteristics and treatment effect estimates for patients included in the RCT versus those excluded.Participants and outcomesThe RCT included hospitalised patients with documented or highly-probable invasive MRSA infections who were randomised to vancomycin versus trimethoprim-sulfamethoxazole (TMP-SMX) treatment, between 2007 and 2014. A concomitant observational study prospectively included all consecutive patients, between 2008 and 2011, who were excluded from the RCT due to no consent, meningitis, left-sided endocarditis, severe neutropaenia, chronic renal dialysis or treatment with study medications for longer than 48 h. The primary outcomes were clinical failure at day 7 and 30-day mortality for both studies. We compared baseline and infection characteristics, outcome rates and treatment effect estimates for included versus excluded patients.ResultsThe RCT included 252 patients who were compared with 220 excluded patients who were observed. Inability to provide informed consent was the main reason for patient exclusion. Excluded patients’ functional and cognitive performance was significantly poorer than that of included patients. Sepsis was more severe among excluded patients (higher rates of mechanical ventilation, indwelling catheters, septic shock and organ failure). Clinical failure occurred in 83/252 (32.9%) versus 175/220 (79.5%) and deaths in 32 (12.7%) versus 64 (29.1%) for included versus excluded patients, p<0.001 for both comparisons. Comparing vancomycin to TMP-SMX, in the RCT mortality, was non-significantly lower with vancomycin (OR 0.76, 95% CIs 0.36 to 1.62), while in the observational analysis of excluded patients, mortality was significantly higher with vancomycin (OR 2.63, 1.04 to 6.65), p=0.04 for the difference.ConclusionsPatient characteristics, outcome event rates and treatment effects differed significantly in the setting of a RCT, despite its pragmatic design, compared to patients treated outside the trial settings.
Understanding trends in blood pressure and their associations with body mass index in Chinese children, from 1985 to 2010: a cross-sectional observational study
Authors: Dong Bin , Wang Zhiqiang , Song Yi , Wang Hai-Jun , Ma Jun 
Published: September 2015

ObjectiveUnderstanding trends in blood pressure (BP) in childhood is crucial to addressing and reducing the burden of adulthood hypertension and associated mortality in the future. In view of growing obesity in Chinese children, we sought to investigate the trends in BP and the influence of body mass index (BMI) on them.Design, setting and participantsWe included 1 010 153 children aged 8–17 years, with completed records from a large national successive cross-sectional survey, the Chinese National Survey on Students’ Constitution and Health, between 1985 and 2010.Main outcome measurementsBP was measured according to the recommendation of the National High Blood Pressure Education Program Working Group, and the elevated BP was based on sex-, age- and height-specific 95th centile of the recommendation.ResultsThe adjusted mean systolic BP in boys and girls decreased by 3.9 and 5.6 mm Hg between 1985 and 2005, and increased by 1.3 and 1.0 mm Hg between 2005 and 2010, respectively. Corresponding adjusted prevalence of elevated systolic BP in boys and girls declined from 5.1% and 5.5% to 3.5% and 2.5% between 1985 and 2005, and increased to 4.9% and 3.5% in 2010, respectively. Adjusted mean BMI of boys and girls in 2010 was 2.0 and 1.2 kg/m2higher than those in 1985, respectively. The prevalence of obesity rose from 0% to 3.4% in boys and 0.9% in girls. Further adjusting for BMI did not change these trends in systolic BP. A similar pattern was also observed in diastolic BP.ConclusionsAfter declining for 20 years, BP levels in Chinese children started to climb upwards. These trends in BP cannot be fully explained by BMI. The investigation of other determinants of BP may provide additional opportunity to curb the current upward BP trend in Chinese children.
Training in General Surgery Ward Call: A Resident-Student Buddy System
Authors: Maurice Andrew , Hann Angus 
Published: September 2015

AbstractThere is a paucity of literature regarding medical student experiences of after hours hospital ward call. It was observed at our institution that medical students had minimal experience in ward call, yet were required to undertake such shifts as interns after graduation. We implemented a buddy system in which a medical student shadowed a general surgery resident for a ward call shift.Final year medical students were recruited from the local university at a tertiary teaching hospital after institutional approval. Each student attended a 4 hour evening shift on a general surgery ward with a supervising resident. A survey detailing attitudes and expectations of ward call was completed before and after the experience.Nine students enrolled in the project. Familiarity of expectations of what is required of an intern on a ward call shift improved significantly after the experience (3.1/5 to 4.1/5, p = 0.002). After hours work experience was reported as useful both before and after the study (4.5/5 to 4.7/5, p = 0.47). Students and doctors involved unanimously felt the experience was worthwhile.After hours ward call experience is useful for a final year medical student. More studies are required to further define the role of after hours ward call experiences during medical training.
Improving the completion of Quality Improvement projects amongst psychiatry core trainees
Authors: Ewins Liz 
Published: September 2015

AbstractQuality Improvement (QI) projects are seen increasingly as more valuable and effective in developing services than traditional audit. However, the development of this methodology has been slower in the mental health field and QI projects are new to most psychiatrists. This project describes a way of engaging trainees across Avon and Wiltshire Mental Health Partnership (AWP) Trust and the Severn School of Psychiatry in QI projects, using QI methodology itself.Through the implementation and development of training sessions and simple, low cost and sustainable interventions over a 10 month period, two thirds of core trainees and over a half of the advanced psychiatry trainees in the School are now participating in 28 individual QI projects and QI project methodology is to become embedded in the core psychiatry training course. As an additional positive outcome, specialty doctors, consultants, foundation doctors, GP trainees, medical students, as well as the wider multidisciplinary team, have all become engaged in QI projects alongside trainees, working with service users and their families to identify problems to tackle and ideas to test.
A multifaceted approach to prevention of delirium on intensive care
Authors: Hanison James , Conway Daniel 
Published: September 2015

AbstractDelirium is a frequent complication of critical illness with an increased risk of death which is difficult to treat effectively. We describe a seven year quality improvement programme that aimed to reduce rates of delirium on intensive care (ICU). We completed two PDSA programmes with a number of changes including alterations to sedation practice and environmental changes to the ICU itself.Rates of delirium reduced from 70% to 44% after the first cycle of change. Rates of delirium were further reduced to 29% after the second cycle of change. The rates are now lower than predicted by the validated prediction tool PRE-DELIRIC.This project demonstrates that a multifaceted approach to prevention of delirium on ICU can deliver sustained reductions in rates of delirium. The impact of the second cycle of change was less than the first, suggesting that further reductions may prove more challenging.
Psychological distress in medical patients seeking ED care for somatic reasons: results of a systematic literature review
Authors: Faessler Lukas , Perrig-Chiello Pasqualina , Mueller Beat , Schuetz Philipp 
Published: September 2015

ObjectivesThe aim of this systematic literature review is to investigate (A) currently used instruments for assessing psychological distress, (B) the prevalence of psychological distress in medical emergency department (ED) patients with acute somatic conditions and (C) empirical evidence on how predictors are associated with psychological distress.MethodsWe conducted an electronic literature search using three databases to identify studies that used validated instruments for detection of psychological distress in adult patients presented to the ED with somatic (non-psychiatric) complaints. From a total of 1688 potential articles, 18 studies were selected for in-depth review.ResultsA total of 13 instruments have been applied for assessment of distress including screening questionnaires and briefly structured clinical interviews. Using these instruments, the prevalence of psychological distress detected in medical ED patients was between 4% and 47%. Psychological distress in general and particularly depression and anxiety have been found to be associated with demographic factors (eg, female gender, middle age) and illness-related variables (eg, urgency of triage category). Some studies reported that coexisting psychological distress of medical patients identified in the ED was associated with physical and psychological health status after ED discharge. Importantly, during routine clinical care, only few patients with psychological distress were diagnosed by their treating physicians.ConclusionsThere is strong evidence that psychological distress is an important and prevalent cofactor in medically ill patients presenting to the ED with harmful associations with (subjective) health outcomes. To prove causality, future research should investigate whether screening and lowering psychological distress with specific interventions would result in better patient outcomes.
Fascin-1 expression as stratification marker in borderline epithelial tumours of the ovary
Authors: El-Balat Ahmed , Arsenic Ruza , Sänger Nicole , Karn Thomas , Becker Sven , Holtrich Uwe , Engels Knut 
Published: September 2015

AimsTo evaluate the actin-bundling protein fascin-1 (FSCN1) as marker for borderline ovarian tumours (BOTs).MethodsWe analysed a retrospective cohort of 140 BOTs with validated diagnosis by an independent pathologist. Immunohistochemical detection of FSCN1 was quantified as combined immunoreactive score (CIS) blinded to clinical patient data. Analyses were first performed for FSCN1 positive versus negative, and then verified using three categories derived from the observed distribution (negative, weak, strong; CIS 0, 1–2, 3–9).ResultsWe detected FSCN1 positivity in 51.4%, and strong expression (CIS 3–9) in 14.3% of the samples. FSCN1 positivity was associated with serous subtype (p<0.001) and micropapillary pattern (p<0.001). Correlation with micropapillary pattern remained significant within the serous BOT (SBOT) subgroup (p=0.022). Strong FSCN1 expression (CIS 3–9) was associated both with the presence of implants (p=0.022), and a higher International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.020).ConclusionsOur analysis links FSCN1 with SBOT with micropapillary pattern. Strong expression is associated with higher FIGO stage and the presence of implants, both related to elevated risk of recurrence. Hence, FSCN1 is an interesting marker worth further analyses of its prognostic value in BOTs.
Activation Status of the Pregnane X Receptor Influences Vemurafenib Availability in Humanized Mouse Models
Authors: MacLeod A. Kenneth , McLaughlin Lesley A. , Henderson Colin J. , Wolf C. Roland 
Published: September 2015

Abstract
Vemurafenib is a revolutionary treatment for melanoma, but the magnitude of therapeutic response is highly variable, and the rapid acquisition of resistance is frequent. Here, we examine how vemurafenib disposition, particularly through cytochrome P450-mediated oxidation pathways, could potentially influence these outcomes using a panel of knockout and transgenic humanized mouse models. We identified CYP3A4 as the major enzyme involved in the metabolism of vemurafenib in in vitro assays with human liver microsomes. However, mice expressing human CYP3A4 did not process vemurafenib to a greater extent than CYP3A4-null animals, suggesting that other pregnane X receptor (PXR)–regulated pathways may contribute more significantly to vemurafenib metabolism in vivo. Activation of PXR, but not of the closely related constitutive androstane receptor, profoundly reduced circulating levels of vemurafenib in humanized mice. This effect was independent of CYP3A4 and was negated by cotreatment with the drug efflux transporter inhibitor elacridar. Finally, vemurafenib strongly induced PXR activity in vitro, but only weakly induced PXR in vivo. Taken together, our findings demonstrate that vemurafenib is unlikely to exhibit a clinically significant interaction with CYP3A4, but that modulation of bioavailability through PXR-mediated regulation of drug transporters (e.g., by other drugs) has the potential to markedly influence systemic exposure and thereby therapeutic outcomes. Cancer Res; 75(21); 4573–81. ©2015 AACR.
Panobinostat for the Treatment of Multiple Myeloma
Authors: Laubach Jacob P. , Moreau Philippe , San-Miguel Jesús F. , Richardson Paul G. 
Published: September 2015

Abstract
Panobinostat is a potent oral deacetylase inhibitor that alters gene expression through epigenetic mechanisms and inhibits protein degradation. It was recently approved by the FDA and EMA for use in combination with bortezomib and dexamethasone in patients with multiple myeloma who have received ≥2 prior regimens, including bortezomib and an immunomodulatory drug. Panobinostat was approved based on results from the phase III PANORAMA 1 trial in patients with relapsed or relapsed and refractory multiple myeloma, which showed that panobinostat plus bortezomib and dexamethasone significantly extended progression-free survival (median, 12.0 months) compared with placebo plus bortezomib and dexamethasone (median, 8.1 months; P &lt; 0.0001). Additional ongoing trials are evaluating panobinostat in combination with other partners in the relapsed/refractory and newly diagnosed treatment settings. This review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. Clin Cancer Res; 21(21); 4767–73. ©2015 AACR.
Seek and Ye Shall Find: Subclonal Anaplastic Lymphoma Kinase Mutations
Authors: George Rani E. 
Published: September 2015

Abstract
Bellini and colleagues demonstrate the importance of next-generation sequencing to uncover subclonal anaplastic lymphoma kinase (ALK) mutations in neuroblastoma. Although the significance of these subclonal aberrations is not yet understood, deep sequencing could identify patients whose tumors may respond to ALK inhibitors. Clin Cancer Res; 21(21); 4747–9. ©2015 AACR.
See related article by Bellini et al., p. 4913
The Contemporary Safety and Effectiveness of Lower Extremity Bypass Surgery and Peripheral Endovascular Interventions in the Treatment of Symptomatic Peripheral Arterial Disease
Authors: Tsai Thomas T. , Rehring Thomas F. , Rogers R. Kevin , Shetterly Susan M. , Wagner Nicole M. , Gupta Rajan , Jazaeri Omid , Hedayati Nasim , Jones W. Schuyler , Patel Manesh R. , Ho P. Michael , Go Alan S. , Magid David J. 
Published: September 2015

Background—
Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) and peripheral endovascular interventions (PVIs); however, limited comparative effectiveness data exist between the 2 therapies. We assessed the safety and effectiveness of LEB and PVI in patients with symptomatic claudication and critical limb ischemia.

Methods and Results—

In a community-based clinical registry at 2 large integrated healthcare delivery systems, we compared 883 patients undergoing PVI and 975 patients undergoing LEB between January 1, 2005 and December 31, 2011. Rates of target lesion revascularization were greater for PVI than for LEB in patients presenting with claudication (12.3±2.7% and 19.0±3.5% at 1 and 3 years versus 5.2±2.4% and 8.3±3.1%, log-rank
P
<0.001) and critical limb ischemia (19.1±4.8% and 31.6±6.3% at 1 and 3 years versus 10.8±2.5% and 16.0±3.2%, log-rank
P
<0.001). However, in comparison with PVI, LEB was associated with increased rates of complications up to 30 days following the procedure (37.1% versus 11.9%,
P
<0.001). There were no differences in amputation rates between the 2 groups. Findings remained consistent in sensitivity analyses by using propensity methods to account for treatment selection.

Conclusions—
In patients with symptomatic peripheral artery disease, in comparison with LEB, PVI was associated with fewer 30-day procedural complications, higher revascularization rates at 1 and 3 years, and no difference in subsequent amputations.
Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis
Authors: Fontana Marianna , Pica Silvia , Reant Patricia , Abdel-Gadir Amna , Treibel Thomas A. , Banypersad Sanjay M. , Maestrini Viviana , Barcella William , Rosmini Stefania , Bulluck Heerajnarain , Sayed Rabya H. , Patel Ketna , Mamhood Shameem , Bucciarelli-Ducci Chiara , Whelan Carol J. , Herrey Anna S. , Lachmann Helen J. , Wechalekar Ashutosh D. , Manisty Charlotte H. , Schelbert Eric B. , Kellman Peter , Gillmore Julian D. , Hawkins Philip N. , Moon James C. 
Published: September 2015

Background—
The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown.

Methods and Results—

Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (
P
<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1–13.7;
P
<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3–13.1;
P
<0.05).

Conclusions—
There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors.
A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis
Authors: Kuhle J , Hardmeier M , Disanto G , Gugleta K , Ecsedi M , Lienert C , Amato MP , Baum K , Buttmann M , Bayas A , Brassat D , Brochet B , Confavreux C , Edan G , Färkkilä M , Fredrikson S , Frontoni M , D’Hooghe M , Hutchinson M , De Keyser J , Kieseier BC , Kümpfel T , Rio J , Polman C , Roullet E , Stolz C , Vass K , Wandinger KP , Kappos L ,   the European Long-term Follow-up Study Group in Interferon β-1b in Secondary-progressive Multiple Sclerosis
Published: September 2015

Objectives: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). Methods: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. Results: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R2: 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited ( R2: 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. Conclusions: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.