Facilitators and barriers of preconception care in women with inflammatory bowel disease and rheumatic diseases: an explorative survey study in a secondary and tertiary hospital.

BACKGROUND: Preconception care (PCC) is care prior to conception to optimize parental health, and health of the future child, through biomedical and behavioral changes. Providing PCC to all women with a wish to conceive will improve perinatal health. PCC is especially important for women with a chronic disease, such as inflammatory bowel disease (IBD) and rheumatic diseases (RD). At present PCC is not part of routine care for these women. The aim of this study is to identify facilitators and barriers on a patient and professional level regarding the provision of PCC in women with IBD and RD. METHODS: An explorative survey study among women with IBD and RD, their treating physicians and obstetric professionals was performed. Patients with a wish to conceive, pregnant women or those with a recent pregnancy (< 1 year ago) visiting the outpatient clinic of a secondary and tertiary hospital and involved physicians and obstetric professionals were eligible. RESULTS: A total of 71% of the IBD patients (n = 22/31) and 35% of the RD patients (n = 20/58) received a PCC consultation. PCC consultation was considered easy to enter, short in time and patients felt comfortable. Patients (71% IBD; 62% RD) preferred a personal PCC consultation with their disease specific specialist together with an obstetrician. Patients specifically wanted to receive information about the safety of medication use and disease activity following delivery. Of the included healthcare professionals 67% (n = 31) agreed PCC was applicable to their patients. Main barrier to providing PCC was lack of time and unavailability of professionals. In total 41% (n = 16) of obstetric professionals felt they had the knowledge and skills to provide PCC compared to 33% (n = 1) and 75% (n = 3) of gastroenterologists and rheumatologists, respectively. CONCLUSION: Lack of awareness and urgency for the effectuation can be seen as important barriers for implementation of PCC. Due to the explorative nature generalisation of the results is not allowed. In the future, adaptation of the curricula of healthcare professionals by implementing interventions for pregnancy planning and preparation will generate awareness. Modelling of the impact of PCC might prove useful in resolving the lack of urgency for PCC realization.

Association of multimorbidity and changes in health-related quality of life following myocardial infarction: a UK multicentre longitudinal patient-reported outcomes study.

BACKGROUND: Multimorbidity is prevalent for people with myocardial infarction (MI), yet previous studies investigated single-health conditions in isolation. We identified patterns of multimorbidity in MI survivors and their associations with changes in HRQoL. METHODS: In this national longitudinal cohort study, we analysed data from 9566 admissions with MI from 77 National Health Service hospitals in England between 2011 and 2015. HRQoL was measured using EuroQol 5 dimension (EQ5D) instrument and visual analogue scale (EQVAS) at hospitalisation, 6, and 12 months following MI. Latent class analysis (LCA) of pre-existing long-term health conditions at baseline was used to identify clusters of multimorbidity and associations with changes in HRQoL quantified using mixed effects regression analysis. RESULTS: Of 9566 admissions with MI (mean age of 64.1 years [SD 11.9], 7154 [75%] men), over half (5119 [53.5%] had multimorbidities. LCA identified 3 multimorbidity clusters which were severe multimorbidity (591; 6.5%) with low HRQoL at baseline (EQVAS 59.39 and EQ5D 0.62) which did not improve significantly at 6 months (EQVAS 59.92, EQ5D 0.60); moderate multimorbidity (4301; 47.6%) with medium HRQoL at baseline (EQVAS 63.08, EQ5D 0.71) and who improved at 6 months (EQVAS 71.38, EQ5D 0.76); and mild multimorbidity (4147, 45.9%) at baseline (EQVAS 64.57, EQ5D 0.75) and improved at 6 months (EQVAS 76.39, EQ5D 0.82). Patients in the severe and moderate groups were more likely to be older, women, and presented with NSTEMI. Compared with the mild group, increased multimorbidity was associated with lower EQ-VAS scores (adjusted coefficient: -5.12 [95% CI -7.04 to -3.19] and -0.98 [-1.93 to -0.04] for severe and moderate multimorbidity, respectively. The severe class was more likely than the mild class to report problems in mobility, OR 9.62 (95% confidence interval: 6.44 to 14.36), self-care 7.87 (4.78 to 12.97), activities 2.41 (1.79 to 3.26), pain 2.04 (1.50 to 2.77), and anxiety/depression 1.97 (1.42 to 2.74). CONCLUSIONS: Among MI survivors, multimorbidity clustered into three distinct patterns and was inversely associated with HRQoL. The identified multimorbidity patterns and HRQoL domains that are mostly affected may help to identify patients at risk of poor HRQoL for which clinical interventions could be beneficial to improve the HRQoL of MI survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT01808027 and NCT01819103.

Modeling human peri-implantation placental development and function†.

It is very difficult to gain a better understanding of the events in human pregnancy that occur during and just after implantation because such pregnancies are not yet clinically detectable. Animal models of human placentation are inadequate. In vitro models that utilize immortalized cell lines and cells derived from trophoblast cancers have multiple limitations. Primary cell and tissue cultures often have limited lifespans and cannot be obtained from the peri-implantation period. We present here two contemporary models of human peri-implantation placental development: extended blastocyst culture and stem-cell derived trophoblast culture. We discuss current research efforts that employ these models and how such models might be used in the future to study the "black box" stage of human pregnancy.

Factors associated with non-essential workplace attendance during the COVID-19 pandemic in the UK in early 2021: evidence from cross-sectional surveys.

OBJECTIVES: Working from home where possible is important in reducing the spread of COVID-19. In early 2021, a quarter of people in England who believed they could work entirely from home reported attending their workplace. To inform interventions to reduce this, this study examined associated factors. STUDY DESIGN: Data from the ongoing COVID-19 Rapid Survey of Adherence to Interventions and Responses survey series of nationally representative samples of people in the UK aged 16+ years in January-February 2021 were used. METHODS: The study sample was 1422 respondents who reported that they could work completely from home. The outcome measure was self-reported workplace attendance at least once during the preceding week. Factors of interest were analysed in three blocks: 1) sociodemographic variables, 2) variables relating to respondents' circumstances and 3) psychological variables. RESULTS: 26.8% (95% confidence interval [CI] = 24.5%-29.1%) of respondents reported having attended their workplace at least once in the preceding week. Sociodemographic variables and living circumstances significantly independently predicted non-essential workplace attendance: male gender (odds ratio [OR] = 1.85, 95% CI = 1.33-2.58); dependent children in the household (OR = 1.65, 95% CI = 1.17-2.32); financial hardship (OR = 1.14, 95% CI = 1.08-1.21); lower socio-economic grade (C2DE; OR = 1.65, 95% CI = 1.19-2.53); working in sectors such as health or social care (OR = 4.18, 95% CI = 2.56-6.81), education and childcare (OR = 2.45, 95% CI = 1.45-4.14) and key public service (OR = 3.78, 95% CI = 1.83-7.81) and having been vaccinated (OR = 2.08, 95% CI = 1.33-3.24). CONCLUSIONS: Non-essential workplace attendance in the UK in early 2021 during the COVID-19 pandemic was significantly independently associated with a range of sociodemographic variables and personal circumstances. Having been vaccinated, financial hardship, socio-economic grade C2DE, having a dependent child at home and working in certain key sectors were associated with higher likelihood of workplace attendance.

"Strong Teeth": an early-phase study to assess the feasibility of an oral health intervention delivered by dental teams to parents of young children.

BACKGROUND: Tooth decay (caries) is a significant health burden in young children. There is strong evidence for the benefits of establishing appropriate home-based oral health behaviours in early childhood. Dental teams are well placed to provide this information and there is clear advice on what oral health information should be given to parents. However, research has shown that there is limited guidance, training and resources on how dental teams should deliver this advice. "Strong Teeth" is a complex oral health intervention, using evidence-based resources and training underpinned by behaviour change psychology, to support behaviour change conversations in dental practice. This early phase evaluation aims to assess the feasibility of this intervention, prior to a full-scale trial. METHODS: The study recruited 15 parents of children aged 0-2-years-old and 21 parents of children aged 3-5 years old, from five NHS dental practices across West Yorkshire. Participant demographics, self-reported brushing behaviours, dietary habits, a dental examination and three objective measures of toothbrushing were collected in a home-setting at baseline, then at 2-weeks and 2-months post-intervention. Recruitment, retention and intervention delivery were analysed as key process outcomes. Brushing habits were compared to national toothbrushing guidelines - the Delivering Better Oral Health toolkit (Public Health England). RESULTS: Strong Teeth was feasible to deliver in a General Dental Practice setting in 94% of cases. Feasibility of recruitment (37%) exceeded progression criterion, however retention of participants (75%) was below the progression criterion for the 0-2 age group. More than half of children recruited aged 3-5-years had caries experience (52%). Total compliance to toothbrushing guidance at baseline was low (28%) and increased after the intervention (52%), an improvement that was statistically significant. Dietary habits remained largely unchanged. Plaque scores significantly decreased in the 3-5-year-olds and toothbrushing duration increased in all age groups. CONCLUSION: "Strong Teeth" intervention delivery and data collection in the home setting was feasible. There was a positive indication of impact on reported toothbrushing behaviours. Some amendments to study design, particularly relating to the inclusion of the 0-2-year-old group, should be considered before progression to a full trial. Trial registration ISRCTN Register: ISRCTN10709150. Registered retrospectively 24/7/2019.

HMGA2 is regulated by LIN28 and BRCA1 in human placental cells.

The chromatin associated transcription factor HMGA2 is a downstream target of let-7 miRNAs and binds to chromatin to regulate gene expression. Inhibition of let-7 miRNAs by RNA-binding proteins LIN28A and LIN28B is necessary during early embryogenesis to ensure stable expression of HMGA2. In addition to LIN28, HMGA2 is regulated by a BRCA1/ZNF350/CtIP repressor complex. In normal tissues, the BRCA1/ZNF350/CtIP complex binds to the HMGA2 promoter to prevent transcription. However, in many cancers the oncomiR miR-182 targets BRCA1, preventing BRCA1 translation and allowing for increased HMGA2. Little is known about the regulation of HMGA2 during early placental development; therefore, we hypothesized that both LIN28 and BRCA1 can regulate HMGA2 in placental cells. Using siRNA and CRISPR gene editing techniques, we found that knockdowns of both LIN28A and LIN28B increase HMGA2 levels in ACH-3P cells. These cells also demonstrated deficiencies in cell differentiation, seemingly differentiating solely towards the syncytiotrophoblast sublineage, secreting higher amounts of hCG, and displaying upregulated ERVW-1. Additionally, we found that a knockout of both LIN28A and LIN28B caused a significant increase of miR-182 and a decrease in BRCA1 allowing HMGA2 mRNA levels to increase and protein levels to remain the same. Using chromatin immunoprecipitation, we saw binding of the BRCA1 repressor complex to HMGA2. We also saw a decrease in binding to HMGA2's promoter in the LIN28A/B knockout cells. These findings suggest a novel role for BRCA1 during early human placental development.

'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.

BACKGROUND: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. OBJECTIVES: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. METHODS: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. RESULTS: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. CONCLUSIONS: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.

Prospective observational cohort study of the association between antiplatelet therapy, bleeding and thrombosis in patients with coronary stents undergoing noncardiac surgery.

BACKGROUND: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). METHODS: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. RESULTS: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93-3.88), P=0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31-3.46), P=0.96. Bleeding was more frequent with DAPT 6.55 (2.3-17.96) P=0.0002. In a propensity matched analysis of 177 patients who received DAPT and 177 monotherapy patients, the risk ratio for MACE with DAPT was 1.83 (0.69-4.85), P=0.32. The risk of bleeding was significantly greater in the DAPT group 4.00 (1.15-13.93), P=0.031. CONCLUSIONS: OBTAIN showed an increased risk of bleeding with DAPT and found no evidence for protective effects of DAPT from perioperative MACE in patients who have undergone previous PCI.

Review of the Ecotoxicological Properties of the Methylenedianiline Substances.

Concerning chronic toxicity, D. magna is the most sensitive species tested against MDA aquatic exposures, with a 21 days-NOEC of 0.00525 mg/L. Exposure of daphnids takes place via the aquatic phase. Other species of the same phylum (Arthropoda) appear to be less sensitive albeit with exposures via soil or sediment, with a 28 days-NOEC of 562 mg/kg d. w. soil (F. candida) and 41.3 mg/kg d. w. sediment (Hyalella azteca), for reproductive and survival endpoints, respectively. Also for acute toxicity, D. magna is more sensitive than the other species, with an 48 h-EC50 that spreads over two orders of magnitude, ranging from 0.019 to 2.7 mg/L. Fish show a more uniform reaction to MDA, with 96 h-LC50 ranging from about 20 to 60 mg/L; chronic data for fish are not available. Acute toxicity data for algae and cyanobacteria are in the range of 1-10 mg/L; based on growth rate, the 72 h-NOECr or ErC10 of MDA to algae is 0.3-9.3 mg/L.For sediment organisms, the black worm L. variegatus shows the highest sensitivity against MDA with a NOEC between ≤3.75 mg/kg and 30 mg/kg d. w., followed by the amphipod H. azteca. The lower sensitivity of L. variegatus in the second study compared to the first study is obviously attributable to the different feeding regimes (semi-continuous feeding against pre-spiked sediment). One argument might be that semi-continuous feeding allows the organisms to avoid the contaminated food. However, a change from semi-continuous feeding to sediment pre-spiked with nettle powder (Urtica sp.) results in an earlier and much stronger increase in ammonia concentration in the system. This became apparent after both studies on the blackworm were finalized. The ammonia 96 h-EC50 for the blackworm is 0.69 mg/L at pH = 8.2, and the 96 h-EC10 at pH = 8.2 is 0.33 mg/L (Hickey and Vickers, Arch Environ Contam Toxicol 26:292-298, 1994). As a result, the lower NOEC and LOEC in the second study with L. variegatus are probably attributable to interference by ammonia.MDA binds irreversibly to soil and sediment which may explain the general, but not uniform lower sensitivity of soil and sediment organisms against aquatic organisms. However, species with intense soil or sediment contact (L. variegatus and E. fetida) show in general lower NOEC values than those organisms with less direct contact (3.75 and 11.2 mg/kg d. w., respectively). On the one hand it may be hypothesized that this intense contact to soil bound MDA is one reason for the higher sensitivity; on the other hand, metabolic capacity against MDA of the organisms tested is unknown at this point in time and might as well explain differences in species sensitivity. For plants there are only acute data available, and in respect to acute toxicity L. sativa is more sensitive to MDA than E. fetida.Limited aquatic data available so far do not indicate that the toxicity of pMDA is different to MDA. In addition, the limited set of data generated with the marine M. macrocopa (crustacean), N. fustulum (diatom) and V. fisheri (bacteria) do not indicate that sea water organisms are more sensitive to MDA than fresh water organisms.In mammals, MDA is unlikely to interact with the endocrine sexual system; interaction with the adrenergic system cannot be ruled out, and effects of MDA on the thyroid hormone system have been demonstrated. MDA inhibits the thyroid peroxidase which might contribute to the thyroid gland tumors observed in chronic studies with rats and mice. Some anti-androgenic activity in in vitro studies with yeast cell did not prevail in in vivo studies with rats and mice.

Regional three-dimensional deformation of human Achilles tendon during conditioning.

Our understanding of in vivo Achilles tendon (AT) conditioning is limited to two-dimensional ultrasound measures of longitudinal deformation of the whole tendon. This study investigated the regional three-dimensional (3D) deformation of the AT during conditioning. Eighteen ATs were scanned using 3D freehand ultrasound during 10 successive 25 s submaximal (50%) voluntary isometric plantarflexion contractions. Longitudinal strain was assessed for the whole AT, aponeurosis, and free AT and transverse strain was assessed for the proximal-, mid-, and distal-portions of the free AT. Longitudinal conditioning of the whole AT was primarily driven by creep response of the free AT and transverse conditioning was greatest for the mid-portion of the free AT. Whole and free AT longitudinal strain increased up to the third contraction and were accompanied by a corresponding reduction in free AT cross-sectional area (CSA) strain in proximal-, mid-, and distal-portions. No significant changes in aponeurosis strain or tendon volume were detected between contractions. These findings suggest that conditioning alters free AT shape, with increased tendon length attained at the expense of reduction in free AT CSA. Although AT experiences different amounts of strain in different regions, the number of contractions required to reach steady-state strain during conditioning is uniform throughout the tendon.

In vivo strain in the deep and superficial regions of the human patellar tendon.

This study investigated strain differences within the patellar tendon (PT) mid-region using an ultrasound-based digital image correlation (DIC) method. Six healthy young participants performed six knee extensions to 60% of maximal voluntary isometric contraction on 2 days. Sagittal ultrasound videos recorded during each contraction were analyzed using the DIC method to determine the strain-torque relationships of the superficial, deep, and whole PT mid-regions. Significantly greater strain was observed in the deep vs superficial layer of the PT mid-region for all contraction intensities, with peak strains of 5.8% (SD 1.7) and 4.5% (SD 1.5), respectively. DIC-based measures of peak tendon strain were repeatable within [intraclass coefficients (ICC) >0.97] and between sessions (ICCs >0.83) and agreed well with the conventional point-to-point method. This study confirmed that significant differences exist between deep and superficial layers of PT mid-region during ramped isometric extensions. These findings support the use of DIC to examine regional strain patterns within the PT mid-region that may be important in the context of tendon injury and adaptation.

Natural disaster management: experience of an academic institution after a 7.8 magnitude earthquake in Ecuador.

OBJECTIVES: This case study describes the implementation of an academic institution's disaster management plan. STUDY DESIGN: Case study. METHODS: USFQ's Medical School developed a six-phase disaster relief plan consisting of: induction, establishing a base camp, crisis management and mental health aid, creation of multidisciplinary teams and multi-agency teams, and reconstruction. Each phase uses a community-oriented approach to foster survivor autonomy and recovery. RESULTS: Our methodology facilitated the successful implementation of multidisciplinary interventions to manage the earthquake's aftermath on the personal, community and regional levels, treated and prevented psychological and physical morbidity among survivors and promoted healthy living conditions and independence. CONCLUSIONS: A multidisciplinary response team that addresses medical needs, mental health, education, food, nutrition and sanitation is highly effective in contributing to timely, effective relief efforts. The short- and long-term solutions we describe could be applicable to other academic centres' interventions in future disaster scenarios around the world.

Molecular Structures of N,N'-Dimethylbenzimidazoline-2-germylene and -stannylene in Solution and in Solid State by Means of Optical (Raman and UV-vis) Spectroscopy and Quantum Chemistry Methods.

X-ray data obtained for germylene 1 evidence its monomeric structure, unlike that of stannylene 2, which had been shown previously to form a coordination dimer. Raman spectra of solid and liquid 1 are identical, whereas the Raman spectra of solid 2 and its solution 2a differ significantly. The spectrum of 2 is complicated and contains the lines corresponding to N → Sn coordination bonds forming a dimer. The spectrum of 2a is simpler and close to that of monomeric 1, thus pointing to the rupture of the dimer in solution. The UV-vis spectrum of solid 2 exhibits a band corresponding to a transition involving the N → Sn coordination bonds. Quantum theory of atoms in molecules data estimate the energy of this bond as ∼19 kcal/mol. The aromaticity of 1 and 2 with their 10 π-electron systems including divalent Ge or Sn atoms is confirmed by negative nucleus-independent chemical shift values.

Changes in Achilles tendon mechanical properties following eccentric heel drop exercise are specific to the free tendon.

Mechanical loading of the Achilles tendon during isolated eccentric contractions could induce immediate and region-dependent changes in mechanical properties. Three-dimensional ultrasound was used to examine the immediate effect of isolated eccentric exercise on the mechanical properties of the distal (free tendon) and proximal (gastrocnemii) regions of the Achilles tendon. Participants (n = 14) underwent two testing sessions in which tendon measurements were made at rest and during a 30% and 70% isometric plantar flexion contractions immediately before and after either: (a) 3 × 15 eccentric heel drops or (b) 10-min rest. There was a significant time-by-session interaction for free tendon length and strain for all loading conditions (P < 0.05). Pairwise comparisons revealed a significant increase in free tendon length and strain at all contraction intensities after eccentric exercise (P < 0.05). There was no significant time-by-session interaction for the gastrocnemii (medial or lateral) aponeurosis or tendon for any of the measured parameters. Immediate changes in Achilles tendon mechanical properties were specific to the free tendon and consistent with changes due to mechanical creep. These findings suggest that the mechanical properties of the free tendon may be more vulnerable to change with exercise compared with the gastrocnemii aponeurosis or tendon.

An international cross-sectional survey of antimicrobial stewardship programmes in hospitals.

OBJECTIVES: To report the extent and components of global efforts in antimicrobial stewardship (AMS) in hospitals. METHODS: An Internet-based survey comprising 43 questions was disseminated worldwide in 2012. RESULTS: Responses were received from 660 hospitals in 67 countries: Africa, 44; Asia, 50; Europe, 361; North America, 72; Oceania, 30; and South and Central America, 103. National AMS standards existed in 52% of countries, 4% were planning them and 58% had an AMS programme. The main barriers to implementing AMS programmes were perceived to be a lack of funding or personnel, a lack of information technology and prescriber opposition. In hospitals with an existing AMS programme, AMS rounds existed in 64%; 81% restricted antimicrobials (carbapenems, 74.3%; quinolones, 64%; and cephalosporins, 58%); and 85% reported antimicrobial usage, with 55% linking data to resistance rates and 49% linking data to infection rates. Only 20% had electronic prescribing for all patients. A total of 89% of programmes educated their medical, nursing and pharmacy staff on AMS. Of the hospitals, 38% had formally reviewed their AMS programme: reductions were reported by 96% of hospitals for inappropriate prescribing, 86% for broad-spectrum antibiotic use, 80% for expenditure, 71% for healthcare-acquired infections, 65% for length of stay or mortality and 58% for bacterial resistance. CONCLUSIONS: The worldwide development and implementation of AMS programmes varies considerably. Our results should inform and encourage the further evaluation of this with a view to promoting a worldwide stewardship framework. The prospective measurement of well-defined outcomes of the impact of these programmes remains a significant challenge.

An orbital period of 0.94 days for the hot-Jupiter planet WASP-18b.

The 'hot Jupiters' that abound in lists of known extrasolar planets are thought to have formed far from their host stars, but migrate inwards through interactions with the proto-planetary disk from which they were born, or by an alternative mechanism such as planet-planet scattering. The hot Jupiters closest to their parent stars, at orbital distances of only approximately 0.02 astronomical units, have strong tidal interactions, and systems such as OGLE-TR-56 have been suggested as tests of tidal dissipation theory. Here we report the discovery of planet WASP-18b with an orbital period of 0.94 days and a mass of ten Jupiter masses (10 M(Jup)), resulting in a tidal interaction an order of magnitude stronger than that of planet OGLE-TR-56b. Under the assumption that the tidal-dissipation parameter Q of the host star is of the order of 10(6), as measured for Solar System bodies and binary stars and as often applied to extrasolar planets, WASP-18b will be spiralling inwards on a timescale less than a thousandth that of the lifetime of its host star. Therefore either WASP-18 is in a rare, exceptionally short-lived state, or the tidal dissipation in this system (and possibly other hot-Jupiter systems) must be much weaker than in the Solar System.

Changes in prevalence of depression and anxiety following smoking cessation: results from an international cohort study (ATTEMPT).

BACKGROUND: Smoking cessation improves physical health but it has been suggested that in vulnerable individuals it may worsen mental health. This study aimed to identify the short- and longer-term effects of stopping smoking on depression and anxiety in the general population and in those with a history of these disorders. METHOD: Sociodemographic and smoking characteristics, and mental and physical health were assessed using established measures in the ATTEMPT cohort, an international longitudinal study of smokers (n = 3645). Smokers who had stopped for at least 3 months or less than 3 months at the 12-month follow-up were compared with current smokers (n = 1640). RESULTS: At follow-up, 9.7% [95% confidence interval (CI) 8.3-11.2] of smokers had stopped for less than 3 months and 7.5% (95% CI 6.3-8.9) for at least 3 months. Compared with current smokers, prevalence of depression prescriptions obtained in the last 2 weeks was lower for those who had stopped for less than 3 months [odds ratio (OR) 0.37, 95% CI 0.14-0.96] or at least 3 months (OR 0.25, 95% CI 0.06-0.94) after adjusting for baseline prescription levels and confounding variables. Adjusted prevalence of recent depression symptoms was also lower for ex-smokers who had stopped for less than 3 months (OR 0.34, 95% CI 0.15-0.78) or at least 3 months (OR 0.24, 95% CI 0.09-0.67) than among continuing smokers. There was no change in anxiety measures in the general population or any increase in anxiety or depression symptoms in ex-smokers with a past history of these conditions. CONCLUSIONS: Smoking cessation does not appear to be associated with an increase in anxiety or depression and may lead to a reduced incidence of depression.

Use of screening tests, diagnosis wait times, and wait-related satisfaction in breast and prostate cancer.

BACKGROUND: Understanding factors relating to the perception of wait time by patients is key to improving the patient experience. METHODS: We surveyed 122 breast and 90 prostate cancer patients presenting at clinics or listed on the cancer registry in Newfoundland and Labrador and reviewed their charts. We compared the wait time (first visit to diagnosis) and the wait-related satisfaction for breast and prostate cancer patients who received regular screening tests and whose cancer was screening test-detected ("screen/screen"); who received regular screening tests and whose cancer was symptomatic ("screen/symptomatic"); who did not receive regular screening tests and whose cancer was screen test-detected ("no screen/screen"); and who did not receive regular screening tests and whose cancer was symptomatic ("no screen/symptomatic"). RESULTS: Although there were no group differences with respect to having a long wait (greater than the median of 47.5 days) for breast cancer patients (47.8% screen/screen, 54.7% screen/symptomatic, 50.0% no screen/ screen, 40.0% no screen/symptomatic; p = 0.814), a smaller proportion of the screen/symptomatic patients were satisfied with their wait (72.5% screen/ screen, 56.4% screen/symptomatic, 100% no screen/ screen, 90.9% no screen/symptomatic; p = 0.048). A larger proportion of screen/symptomatic prostate cancer patients had long waits (>104.5 days: 41.3% screen/screen, 92.0% screen/symptomatic, 46.0% no screen/screen, 40.0% no screen/symptomatic; p = 0.011) and a smaller proportion of screen/ symptomatic patients were satisfied with their wait (71.2% screen/screen, 30.8% screen/symptomatic, 76.9% no screen/screen, 90.9% no screen/symptomatic; p = 0.008). CONCLUSIONS: Diagnosis-related wait times and satisfaction were poorest among patients who received regular screening tests but whose cancer was not detected by those tests.

The impact of traumatic pelvic fractures on sporting activity and quality of life.

BACKGROUND: Pelvic fractures (PFX) reflect high-energy trauma with high mortality and morbidity. AIM: We attempted to determine: whether there is a decrease in levels of sporting and physical activity in patients with operatively-treated PFX; risk factors for decreased sporting activity; any correlation between sporting activity and quality of life in this group. METHODS: Retrospective demographics on mechanism of injury, fracture type, associated injury and injury severity score, as well as prospective documentation of the level and frequency of sporting activity, were collected from adult patients treated operatively for a PFX between 2007 and 2010, using a specifically designed questionnaire. Quality of life before and after injury was also recorded using the EuroQol-5D health-outcome tool. RESULTS: 80 patients without pre-existing musculoskeletal disability were enrolled. The mean age was 44.9 years (18-65). The mean follow-up was 30.5 months (12-39). A decrease in level and frequency of sporting activity was observed. It was associated with lower-extremity associated injuries, but not with injury severity score, PFX severity, PFX type, age, or timing of follow-up. Sporting activity before injury predicted higher levels of sporting participation after injury. Decreased sporting activity after injury was associated with decreased EuroQol-SD score. CONCLUSIONS: Patients should be counselled on the likelihood of a reduction in sporting activities after surgically treated PFX. A larger multi-centre study is needed to further expand on the evidence of the true impact of PFX and its associated injuries on sporting activity.

What is the effect of penicillin dosing interval on outcomes in streptococcal infective endocarditis?

OBJECTIVES: Penicillin is an important treatment option for streptococcal infective endocarditis (IE), but its short half-life requires frequent re-dosing (4- or 6-hourly). There is a variation between the dosing regimens in different guidelines and consequent differences in the dosing interval. The objective of this study was to examine the relationship between the penicillin dosing interval and outcomes in streptococcal IE. METHODS: A retrospective study of cases of streptococcal IE was undertaken using the Leeds Endocarditis Service database. Cases were included if the first-line therapy had been penicillin and excluded if patients had received less than 72 h of therapy. Details of antimicrobial therapy and outcomes were collated using strict definitions. Various parameters were considered as independent variables in a multivariate logistic regression analysis. Univariate analysis of categorical data was carried out using a χ(2) test, and analysis of continuous data using an unpaired t-test. RESULTS: Two hundred and twelve cases were included in the final analysis. Of the parameters considered, a 4-hourly dosing interval [unadjusted OR = 2.79 (95% CI 1.43-5.62)] and initial echocardiographic evidence of abscess or severe valve regurgitation [unadjusted OR = 0.30 (95% CI 0.13-0.66)] were the only statistically significant factors associated with the success or failure of penicillin therapy. The odds of a successful outcome were almost three times greater with a 4-hourly regimen than with a 6-hourly regimen. Failure of penicillin therapy had no correlation with the MIC of penicillin or the concurrent administration of gentamicin. CONCLUSIONS: Penicillin continues to be an effective therapy for IE. This study suggests that a 4-hourly dosing interval may be relevant in predicting the success of initial medical therapy. Further prospective studies are warranted to evaluate relationships in more detail.