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IntroductionThe History, Electrocardiogram (ECG), Age, Risk Factors and Troponin (HEART) score is commonly used to risk stratify patients with possible myocardial infarction as low risk or high risk in the Emergency Department (ED). Whether the HEART score can be used by paramedics to guide care were high-sensitivity cardiac troponin testing available in a prehospital setting is uncertain.MethodsIn a prespecified secondary analysis of a prospective cohort study where paramedics enrolled patients with suspected myocardial infarction, a paramedic Heart, ECG, Age, Risk Factors (HEAR) score was recorded contemporaneously, and a prehospital blood sample was obtained for subsequent cardiac troponin testing. HEART and modified HEART scores were derived using laboratory contemporary and high-sensitivity cardiac troponin I assays. HEART and modified HEART scores of ≤3 and ≥7 were applied to define low-risk and high-risk patients, and performance was evaluated for an outcome of major adverse cardiac events (MACEs) at 30 days.ResultsBetween November 2014 and April 2018, 1054 patients were recruited, of whom 960 (mean 64 (SD 15) years, 42% women) were eligible for analysis and 255 (26%) experienced a MACE at 30 days. A HEART score of ≤3 identified 279 (29%) as low risk with a negative predictive value of 93.5% (95% CI 90.0% to 95.9%) for the contemporary assay and 91.4% (95% CI 87.5% to 94.2%) for the high-sensitivity assay. A modified HEART score of ≤3 using the limit of detection of the high-sensitivity assay identified 194 (20%) patients as low risk with a negative predictive value of 95.9% (95% CI 92.1% to 97.9%). A HEART score of ≥7 using either assay gave a lower positive predictive value than using the upper reference limit of either cardiac troponin assay alone.ConclusionsA HEART score derived by paramedics in the prehospital setting, even when modified to harness the precision of a high-sensitivity assay, does not allow safe rule-out of myocardial infarction or enhanced rule-in compared with cardiac troponin testing alone.

Background: Inguinal hernia has a lifetime incidence of 27% in men and 3% in women. Surgery is the recommended treatment, but there is no consensus on the best method. Open repair is most popular, but there are concerns about the risk of chronic groin pain. Laparoscopic repair is increasingly accepted due to the lower risk of chronic pain, although its recurrence rate is still unclear. The aim of this overview is to compare the risk of recurrence and chronic groin pain in laparoscopic versus open repair for inguinal hernia. Methods: We searched Ovid MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews for systematic reviews and meta-analyses. Only reviews of randomised controlled trials (RCTs) in adults published in English were included. Conference proceedings and editorials were excluded. The quality of the systematic reviews was assessed using the AMSTAR 2 checklist. Two outcomes were considered: hernia recurrence and chronic pain. Results: Twenty-one systematic reviews and meta-analyses were included. Laparoscopic repair was associated with a lower risk of chronic groin pain compared with open repair. In the four systematic reviews assessing any laparoscopic versus any open repairs, laparoscopic repair was associated with a statistically significant (range: 26–46%) reduction in the odds or risk of chronic pain. Most reviews showed no difference in recurrence rates between laparoscopic and open repairs, regardless of the types of repair considered or the types of hernia that were studied, but most reviews had wide confidence intervals and we cannot rule out clinically important effects favouring either type of repair. Conclusion: Meta-analyses suggest that laparoscopic repairs have a lower incidence of chronic groin pain than open repair, but there is no evidence of differences in recurrence rates between laparoscopic and open repairs.

The benefit of fractional exhaled nitric oxide (FeNO) in guiding asthma treatment is uncertain. We evaluated the efficacy of adding FeNO to symptom-guided treatment in children with asthma versus only symptom-guided treatment.

[PdI2(μ-PPh2)(μ2-OAc)(PPh3)2] is the reduction product of PdII(OAc)2(PPh3)2, generated by reaction of ‘Pd(OAc)2’ with two equivalents of PPh3. Here, we report that the reaction of [PdI2(μ-PPh2)(μ2-OAc)(PPh3)2] with PPh3results in a nuanced disproportionation reaction, forming [Pd0(PPh3)3] and a phosphinito-bridged PdI-dinuclear complex, namely [PdI2(μ-PPh2){κ2-P,O-μ-P(O)Ph2}(κ-PPh3)2]. The latter complex is proposed to form by abstraction of an oxygen atom from an acetate ligand at Pd. A mechanism for the formal reduction of a putative PdIIdisproportionation species to the observed PdIcomplex is postulated. Upon reaction of the mixture of [Pd0(PPh)3] and [PdI2(μ-PPh2){κ2-P,O-μ-P(O)Ph2}(κ-PPh3)2] with 2-bromopyridine, the former Pd0complex undergoes a fast oxidative addition reaction, while the latter dinuclear PdIcomplex converts slowly to a tripalladium cluster, of the type [Pd3(μ-X)(μ-PPh2)2(PPh3)3]X, with an overall 4/3 oxidation state perPd. Our findings reveal complexity associated with the precatalyst activation step for the ubiquitous ‘Pd(OAc)2’/nPPh3catalyst system, with implications for cross-coupling catalysis.

To determine whether risk stratification in the out-of-hospital setting could identify patients with chest pain who are at low and high risk to avoid admission or aid direct transfer to cardiac centers.

Heavy menstrual bleeding affects 25% of women in the UK, many of whom require surgery to treat it. Hysterectomy is effective but has more complications than endometrial ablation, which is less invasive but ultimately leads to hysterectomy in 20% of women. We compared laparoscopic supracervical hysterectomy with endometrial ablation in women seeking surgical treatment for heavy menstrual bleeding.

To establish the incidence of Stargardt disease (STGD) in the United Kingdom and define baseline characteristics of newly diagnosed patients.

Purpose To evaluate the influence of socioeconomic factors on visual acuity before cataract surgery.Methods The medical case notes of 240 consecutive patients listed for cataract surgery from January 1, 2010, at Grampian University Hospital, Aberdeen, were reviewed retrospectively. Patients with ocular comorbidity were excluded. Demographics, postal codes, and visual acuity were recorded. Scottish Index of Multiple Deprivation was used to determine the deprivation rank. Home location was classified as urban or rural. The effect of these parameters on preoperative visual acuity was investigated using chi-square tests or Fisher exact test as appropriate.Results A total of 184 patients (mean 75 years) were included. A total of 127 (69%) patients had visual acuity of 6/12 or better. An association was found between affluence and preoperative visual acuity of 6/12 or better (χ2trend= 4.97, p = 0.03), with a significant rising trend across quintile of deprivation. There was no evidence to suggest association between geographical region and preoperative visual acuity (p = 0.63).Conclusions Affluence was associated with good visual acuity (6/12 or better) before cataract surgery. There was no difference in preoperative visual acuity between rural and urban populations.

Small bowel angiodysplasia accounts for 30 to 40 of cases of obscure gastrointestinal bleeding and is associated with significant morbidity and mortality. Identifying lesions can be difficult. Small bowel capsule endoscopy (SBCE) is a significant advance on earlier diagnostic techniques. The cause of angiodysplasia is unknown and the natural history poorly understood. Many lesions are thought to arise from a degenerative process associated with ageing, local vascular anomalies, and tissue hypoxia. Nonpathologic lymphangiectasias are commonly seen throughout the small bowel and are considered a normal finding.

OBJECTIVE: To quantify the relationship between Stanford Health Assessment Questionnaire (HAQ) disability and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: A consecutive series of 114 patients with RA but without overt arterial disease, aged 40–65 years, were recruited from rheumatology clinics. A research nurse measured blood pressure (BP), arterial stiffness (heart rate-adjusted augmentation index), fasting lipids, glucose, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). A self-completed patient questionnaire included HAQ, damaged joint count, EuroQol measure of health outcome, and Godin physical activity score. Multiple linear regression (MLR) adjusted for age, sex, smoking pack-years, cholesterol, mean arterial BP, physical activity, daily fruit and vegetable consumption, arthritis duration, ESR, and RA criteria. RESULTS: Mean age was 54 years (81% women) with a median HAQ of 1.13 (interquartile range 0.50; 1.75). Median RA duration was 10 years, 83% were RF-positive, and median ESR was 16 mm/h. Mean arterial stiffness was 31.5 (SD 7.7), BP 125/82 mm Hg, cholesterol 5.3 mmol/l, and 24% were current smokers. Current therapy included RA disease-modifying agents (90%), prednisolone (11%), and antihypertensive therapy (18%). Arterial stiffness was positively correlated with HAQ (r = 0.42; 95% CI 0.25 to 0.56). On MLR, a 1-point increase in HAQ disability was associated with a 2.8 increase (95% CI 1.1 to 4.4; p = 0.001) in arterial stiffness. Each additional damaged joint was associated with a 0.17 point increase (95% CI 0.04 to 0.29; p = 0.009) in arterial stiffness. The relationship between EuroQol and arterial stiffness was not statistically significant. CONCLUSION: In patients with RA who are free of overt arterial disease, higher RA disability is associated with increased arterial stiffness independently of traditional cardiovascular risk factors and RA characteristics.

Despite being one of the most common adverse obstetric outcomes, 9.5% to 50.2% of stillbirths are classified as unexplained. Although this may be due in part to the many complex interacting factors that contribute to fetal death, there is also still great uncertainty surrounding stillbirth recurrence risks, with studies reporting inconsistent rates, from 2- to 10-fold. In this systematic review and meta-analysis, authors examine possible associations between stillbirth in an initial pregnancy and risk of stillbirth in subsequent pregnancies, in attempts to clarify some of these concerns.This study was a meta-analysis and systematic review of recurrent stillbirth; stillbirth was defined as fetal death occurring at more than 20 weeks’ gestation or a birth weight of at least 400 g. To prevent distortion of findings from variations in clinical practice and health care accessibility, only studies from high-income countries were used. A total of 16 studies, published between 2001 and 2014, were included in this analysis (13 cohort studies and 3 case-control studies).A total of 3,412,079 women were included in these 16 studies; 99.3% had a live birth, and 0.7% had a stillbirth in the initial pregnancy. Of the women with initial live births, 0.4% experienced a subsequent stillbirth, whereas of the women with initial stillbirths, 2.5% experienced a subsequent stillbirth. Pooled adjusted and unadjusted odds ratios (3.38 and 4.44, respectively) both indicated increased risk of subsequent stillbirth in women with previous history of stillbirth. When analysis was restricted to the 12 studies that specifically examined risk of stillbirth recurrence in women with first and second subsequent pregnancies, the risk was still 4.77-fold. Four of the studies addressed risk of recurrence of unexplained stillbirth, although methodological differences in the study prevented subgroup analysis. Nevertheless, the odds ratios in each of these studies ranged from 1.00 to 4.18, indicating increased recurrence risk. This trend was also true in the sensitivity analyses, which adjusted for confounding factors. Risk was slightly attenuated when adjusting for maternal characteristics only. However, this is not of clinical significance as previous studies have shown that much of recurrence risk cannot be explained by modifiable maternal factors.Overall, this comprehensive review and meta-analysis supports previous findings that women who experience stillbirth in their initial pregnancy are at higher risk of stillbirth in a subsequent pregnancy. Some limitations of the review are high heterogeneity of studies and possible publication bias, where smaller studies with large effects may be underrepresented.

Site-selective dihalogenated heteroarene cross-coupling with organometallic reagents usually occurs at the halogen proximal to the heteroatom, enabled by intrinsic relative electrophilicity, particularly in strongly polarized systems. An archetypical example is the Suzuki–Miyaura cross-coupling (SMCC) of 2,4-dibromopyridine with organoboron species, which typically exhibit C2-arylation site-selectivity using mononuclear Pd (pre)catalysts. Given that Pd speciation, particularly aggregation, is known to lead to the formation of catalytically competent multinuclear Pdnspecies, the influence of these species on cross-coupling site-selectivity remains largely unknown. Herein, we disclose that multinuclear Pd species, in the form of Pd3-type clusters and nanoparticles, switch arylation site-selectivity from C2 to C4, in 2,4-dibromopyridine cross-couplings with both organoboronic acids (SMCC reactions) and Grignard reagents (Kumada-type reactions). The Pd/ligand ratio and the presence of suitable stabilizing salts were found to be critically important in switching the site-selectivity. More generally, this study provides experimental evidence that aggregated Pd catalyst species not only are catalytically competent but also alter reaction outcomes through changes in product selectivity.

Tripalladium clusters of the type [Pd3(PPh3)4]2+, wherein three linearly connected Pd atoms are stabilized by phosphine and arsine ligands, have been detected and isolated as intermediates during the reduction of well-defined mononuclear [Pd(OTf)2(XPh3)2] (X = P and X = As, respectively) to Pd nanoparticles (PdNPs). The isolated [Pd3(PPh3)4]2+cluster isomerizes on broad-band UV irradiation to form an unexpected photoisomer, produced by a remarkable change in conformation at one of the bridging PPh3ligands. A catalytic role for these [Pd3(XPh3)4]2+species is exemplified in Suzuki–Miyaura cross-coupling (SMCC) reactions, with high activity seen in the arylation of a brominated heterocyclic 2-pyrone. Use of the [Pd3(PPh3)4]2+cluster enables a switch in site selectivity for SMCC reactions involving 2,4-dibromopyridine from the typical C2-bromide site (seen previously for mononuclear Pd catalysts) to the atypical C4-bromide site, thereby mirroring recently reported cyclic Pd3clusters and PdNPs. We have further determined that the thermal isomer and photoisomer of [Pd3(PPh3)4]2+are similarly catalytically active in the Pd-catalyzed hydrogenation of phenylacetylene to give styrene. Our findings link the evolution of mononuclear Pd(II) salts to PdNPs via the intermediacy of linear [Pd3(XPh3)4]2+clusters.

ObjectiveTo determine the risk of recurrent stillbirth.DesignSystematic review and meta-analysis of cohort and case-control studies.Data sourcesEmbase, Medline, Cochrane Library, PubMed, CINAHL, and Scopus searched systematically with no restrictions on date, publication, or language to identify relevant studies. Supplementary efforts included searching relevant internet resources as well as hand searching the reference lists of included studies. Where published information was unclear or inadequate, corresponding authors were contacted for more information.Study selectionCohort and case-control studies from high income countries were potentially eligible if they investigated the association between stillbirth in an initial pregnancy and risk of stillbirth in a subsequent pregnancy. Stillbirth was defined as fetal death occurring at more than 20 weeks’ gestation or a birth weight of at least 400 g. Two reviewers independently screened titles to identify eligible studies based on inclusion and exclusion criteria agreed a priori, extracted data, and assessed the methodological quality using scoring criteria from the critical appraisal skills programme. Random effects meta-analyses were used to combine the results of the included studies. Subgroup analysis was performed on studies that examined unexplained stillbirth.Results13 cohort studies and three case-control studies met the inclusion criteria and were included in the meta-analysis. Data were available on 3 412 079 women with pregnancies beyond 20 weeks duration, of who 3 387 538 (99.3%) had had a previous live birth and 24 541 (0.7%) a stillbirth. A total of 14 283 stillbirths occurred in subsequent pregnancies, 606/24 541 (2.5%) in women with a history of stillbirth and 13 677/3 387 538 (0.4%) among women with no such history (pooled odds ratio 4.83, 95% confidence interval 3.77 to 6.18). 12 studies specifically assessed the risk of stillbirth in second pregnancies. Compared with women who had a live birth in their first pregnancy, those who experienced a stillbirth were almost five times more likely to experience a stillbirth in their second pregnancy (odds ratio 4.77, 95% confidence interval 3.70 to 6.15). The pooled odds ratio using the adjusted effect measures from the primary studies was 3.38 (95% confidence interval 2.61 to 4.38). Four studies examined the risk of recurrent unexplained stillbirth. Methodological differences between these studies precluded pooling the results.ConclusionsThe risk of stillbirth in subsequent pregnancies is higher in women who experience a stillbirth in their first pregnancy. This increased risk remained after adjusted analysis. Evidence surrounding the recurrence risk of unexplained stillbirth remains controversial.