To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Nearly half of care home residents with advanced dementia have clinically significant agitation. Little is known about costs associated with these symptoms toward the end of life. We calculated monetary costs associated with agitation from UK National Health Service, personal social services, and societal perspectives.
Prospective cohort study.
Thirteen nursing homes in London and the southeast of England.
Seventy-nine people with advanced dementia (Functional Assessment Staging Tool grade 6e and above) residing in nursing homes, and thirty-five of their informal carers.
Data collected at study entry and monthly for up to 9 months, extrapolated for expression per annum. Agitation was assessed using the Cohen-Mansfield Agitation Inventory (CMAI). Health and social care costs of residing in care homes, and costs of contacts with health and social care services were calculated from national unit costs; for a societal perspective, costs of providing informal care were estimated using the resource utilization in dementia (RUD)-Lite scale.
After adjustment, health and social care costs, and costs of providing informal care varied significantly by level of agitation as death approached, from £23,000 over a 1-year period with no agitation symptoms (CMAI agitation score 0–10) to £45,000 at the most severe level (CMAI agitation score >100). On average, agitation accounted for 30% of health and social care costs. Informal care costs were substantial, constituting 29% of total costs.
With the increasing prevalence of dementia, costs of care will impact on healthcare and social services systems, as well as informal carers. Agitation is a key driver of these costs in people with advanced dementia presenting complex challenges for symptom management, service planners, and providers.
Balloon Eustachian tuboplasty is a surgical management option for Eustachian tube dysfunction; it has shown promising results in studies worldwide, but has had limited uptake in the UK. This study reports long-term outcomes for patients offered balloon Eustachian tuboplasty for chronic dilatory and baro-challenge-induced Eustachian tube dysfunction, and describes practical experience gained from its implementation.
Balloon Eustachian tuboplasty was conducted in 25 patients (36 ears) with Eustachian tube dysfunction over three years. Information on presenting symptoms and signs, audiometric findings, tympanometry, and Eustachian Tube Dysfunction Questionnaire-7 scores were recorded pre- and post-operatively with a minimum follow up of one year.
Sixteen (64 per cent) of the 25 patients demonstrated symptom resolution after balloon Eustachian tuboplasty according to the Eustachian Tube Dysfunction Questionnaire-7. Fourteen (64 per cent) of the 22 patients with a type B or C tympanogram pre-operatively, had a type A trace post-operatively. Fifteen (75 per cent) of 20 patients with pre-operative conductive hearing loss showed improvement post-operatively, and 11 (50 per cent) of 22 patients with pre-operative middle-ear effusion or tympanic membrane retraction showed resolution.
Balloon Eustachian tuboplasty can improve subjective and objective measures of Eustachian tube dysfunction, and provide longer-term resolution.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
This research seeks to understand the economic and social interaction patterns among dispersed Piedmont Village Tradition communities in the North American Southeast, AD 1200–1600. Piedmont Village Tradition communities lived adjacent to Mississippian societies and have been categorized as a peripheral society because of this spatial relationship. We examine economic behaviors by constructing fall-off curves of local versus nonlocal lithic material proportions at settlement sites and examining the reduction behaviors and tool types at sites. The results support a possible gateway model for the acquisition and distribution of nonlocal materials that linked spatially proximate communities. To examine social interaction patterns, we conducted a Brainerd-Robinson analysis of ceramic attributes from six sites and combined our results with work by Rogers (1993). The results show sites with stylistic similarities are not the same sites that share lithic resources. We conclude that these spatially non-overlapping artifact patterns result from a heterarchical social organization with a high degree of independence between economic and social interactions. Finally, we contextualize our results within the current knowledge of Mississippian and Piedmont Village Tradition societies in the region to broaden the discussion of gateways in reciprocity-based economies, societies traditionally thought of as peripheral to complex societies, and coalescence.
Clonal Mycobacterium mucogenicum isolates (determined by molecular typing) were recovered from 19 bronchoscopic specimens from 15 patients. None of these patients had evidence of mycobacterial infection. Laboratory culture materials and bronchoscopes were negative for Mycobacteria. This pseudo-outbreak was caused by contaminated ice used to provide bronchoscopic lavage. Control was achieved by transitioning to sterile ice.
Sexually transmitted infections (STIs) can be found in a range of hosts. Their epidemiology is predicted to vary with mean and variance in number of mating partners and, in more refined models, contact and social structure. Weak dependence of mating rate on host density leads to a prediction of density-independent dynamics, including the possibility that sterilising infections could drive their hosts extinct. Infection’s impact on the host is predicted to select for mate choice against infected partners and reduced mating rates. We examine these predictions against STIs in nature, with a particular focus on studies of beetle–ectoparasitic mite interactions. The Adalia bipunctata–Coccipolipus interaction has given rich insights, with ease of scoring infection and mating activity in natural populations enabling detailed documentation of dynamics. Laboratory study has allowed precise estimation of transmission parameters to inform models and focused analysis of behaviour. These studies have confirmed the core impact of mating rate on STI dynamics, but revealed unexpected drivers such as food supply (positively driving mating rate) and sex ratio (enhancing spread and producing male-biased prevalence), alongside constraints on spread from host phenology.
Since its emergence, devil facial tumour disease (DFTD) has spread throughout most of the geographic range of the Tasmanian devil, causing >90% local population decline, >80% overall decline and cascading effects on the ecosystem. We developed a decision tree to guide research and management of this cancer. The devil–DFTD system gives an opportunity to study a wildlife disease in all stages of existence across the entire geographic range of a natural host. Despite predictions of extinction, devils persist. State–space models show that individuals with higher fitness (the larger, more dominant individuals responsible for most of the biting) are more likely to become infected themselves. Individual-based models in which demographic parameters depend on the size of the tumours carried by individual hosts show that DFTD epidemics operate on a much slower timescale than those of viral or bacterial diseases. Following an initial epidemic peak, the consequences for a general epidemic may be coexistence, even in the absence of evolutionary changes in either host or pathogen. Multiple lines of evidence show that Tasmanian devils are evolving in response to DFTD. Conservation efforts are now shifting from managing for extinction to managing for persistence.
Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).
We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.
There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.
These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.
There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.
We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.
We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.
Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).
These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.
Declaration of interest
W.v.d.B received fees in the past 3 years from Indivior, C&A Pharma, Opiant and Angelini. G.M.G. is a National Institute for Health Research (NIHR) Emeritus Senior Investigator, holds shares in P1vital and has served as consultant, advisor or CME speaker in the past 3 years for Allergan, Angelini, Compass Pathways, MSD, Lundbeck (/Otsuka and /Takeda), Medscape, Minervra, P1Vital, Pfizer, Sage, Servier, Shire and Sun Pharma.
We analyzed antibiotic use data from 29 southeastern US hospitals over a 5-year period to determine changes in antibiotic use after the fluoroquinolone US Food and Drug Administration (FDA) advisory update in 2016. Fluoroquinolone use declined both before and after the FDA announcement, and the use of select, alternative antibiotics increased after the announcement.
Fluoroquinolones are among the 4 most commonly prescribed antibiotic classes.1,2 Postmarketing reports of serious adverse events linked to fluoroquinolones include tendonitis, neuropathy, hypoglycemia, psychiatric side effects, and possible aortic vessel rupture, leading to safety label changes in July 2008 and August 2013.3 In July 2016, the US Food and Drug Administration (FDA) strengthened the “black box” warning following an initial safety announcement in May 2016, recommending avoidance of fluoroquinolones for uncomplicated infections such as acute exacerbation of chronic bronchitis, uncomplicated urinary tract infections, and acute bacterial sinusitis.4 Concerns over safety and the association with Clostridiodes difficile infection have led inpatient antimicrobial stewardship programs (ASPs) to develop initiatives to promote avoidance of quinolones. The objective of this study was to quantify the effect of the 2016 FDA “black box” update on inpatient antibiotic use among a cohort of southeastern US hospitals.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1.Explore the current molecular landscape of pediatric high grade gliomas
2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3.Discuss the current status of NTRK inhibitor clinical trials
The sternocleidomastoid can be used as a pedicled flap in head and neck reconstruction. It has previously been associated with high complication rates, likely due in part to the variable nature of its blood supply.
To provide clinicians with an up-to-date review of clinical outcomes of sternocleidomastoid flap surgery in head and neck reconstruction, integrated with a review of vascular anatomical studies of the sternocleidomastoid.
A literature search of the Medline and Web of Science databases was conducted. Complications were analysed for each study. The trend in success rates was analysed by date of the study.
Reported complication rates have improved over time. The preservation of two vascular pedicles rather than one may have contributed to improved outcomes.
The sternocleidomastoid flap is a versatile option for patients where prolonged free flap surgery is inappropriate. Modern vascular imaging techniques could optimise pre-operative planning.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
To describe and compare caffeinated energy drink adverse event (AE) report/exposure call data from the US Food and Drug Administration Center for Food Safety and Applied Nutrition’s Adverse Event Reporting System (CAERS) and the American Association of Poison Control Centers’ National Poison Data System (NPDS).
Data were evaluated from US-based CAERS reports and NPDS exposure calls, including report/exposure call year, age, sex, location, single v. multiple product consumption, outcome, symptom, intentionality (NPDS only), report type, product name (CAERS only).
The analysis defined participants (cases) by the number of caffeinated energy drink products indicated in each AE report or exposure call. Single product cases included 357 from CAERS and 12 822 from NPDS; multiple product cases included 153 from CAERS and 931 from NPDS.
CAERS v. NPDS single product cases were older and more frequently indicated serious symptoms. Multiple v. single product consumers were older in both. In CAERS, unlike NPDS, most multiple product consumers were female. CAERS single v. multiple product reports cited higher proportions of life-threatening events, but less often indicated hospitalization and serious events. NPDS multiple v. single product cases involved fewer ≤5-year-olds and were more often intentional.
Despite limitations, both data sources contribute to post-market surveillance and improve understanding of public health concerns.
To examine the association between parenting styles and overall child dietary quality within households that are low-income and food-insecure.
Child dietary intake was measured via a 24 h dietary recall. Dietary quality was assessed using the Healthy Eating Index-2005 (HEI-2005). Parenting styles were measured and scored using the Parenting Styles and Dimensions Questionnaire. Linear regressions were used to test main and interaction associations between HEI-2005 scores and parenting styles.
Non-probability sample of low-income and food-insecure households in South Carolina, USA.
Parent–child dyads (n 171). Parents were ≥18 years old and children were 9–15 years old.
We found a significant interaction between authoritative and authoritarian parenting style scores. For those with a mean authoritarian score, each unit increase in authoritative score was associated with a higher HEI-2005 score (b = 3·36, P < 0.05). For those with an authoritarian score that was 1 sd above the mean authoritarian score, each unit increase in authoritative score was associated with a higher HEI-2005 score (b = 8.42, P < 0.01). For those with an authoritarian score that was −1 sd below the mean authoritarian score, each unit increase in authoritative score was associated with a lower HEI-2005 score; however, this was not significant (b = −1·69, P > 0·05). Permissive parenting style scores were negatively associated with child dietary quality (b = −2·79, P < 0·05).
Parenting styles should be considered an important variable that is associated with overall dietary quality in children living within low-income and food-insecure households.
Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.
Young people with 22q11.2 deletion syndrome (22q11.2DS) are at high risk for neurodevelopmental disorders. Sleep problems may play a role in this risk but their prevalence, nature and links to psychopathology and cognitive function remain undescribed in this population.
Sleep problems, psychopathology, developmental coordination and cognitive function were assessed in 140 young people with 22q11.2DS (mean age = 10.1, s.d. = 2.46) and 65 unaffected sibling controls (mean age = 10.8, s.d.SD = 2.26). Primary carers completed questionnaires screening for the children's developmental coordination and autism spectrum disorder.
Sleep problems were identified in 60% of young people with 22q11.2DS compared to 23% of sibling controls (OR 5.00, p < 0.001). Two patterns best-described sleep problems in 22q11.2DS: restless sleep and insomnia. Restless sleep was linked to increased ADHD symptoms (OR 1.16, p < 0.001) and impaired executive function (OR 0.975, p = 0.013). Both patterns were associated with elevated symptoms of anxiety disorder (restless sleep: OR 1.10, p = 0.006 and insomnia: OR 1.07, p = 0.045) and developmental coordination disorder (OR 0.968, p = 0.0023, and OR 0.955, p = 0.009). The insomnia pattern was also linked to elevated conduct disorder symptoms (OR 1.53, p = 0.020).
Clinicians and carers should be aware that sleep problems are common in 22q11.2DS and index psychiatric risk, cognitive deficits and motor coordination problems. Future studies should explore the physiology of sleep and the links with the neurodevelopment in these young people.
Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions’ feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols.
Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals.
Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates.
High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.
Ultrasound applications are widespread, and their utility in resource-limited environments are numerous. In disasters, the use of ultrasound can help reallocate resources by guiding decisions on management and transportation priorities. These interventions can occur on-scene, at triage collection points, during transport, and at the receiving medical facility. Literature related to this specific topic is limited. However, literature regarding prehospital use of ultrasound, ultrasound in combat situations, and some articles specific to disaster medicine allude to the potential growth of ultrasound utilization in disaster response.
To evaluate the utility of point-of-care ultrasound in a disaster response based on studies involving ultrasonography in resource-limited environments.
A narrative review of MEDLINE, MEDLINE InProcess, EPub, and Embase found 20 articles for inclusion.
Experiences from past disasters, prehospital care, and combat experiences have demonstrated the value of ultrasound both as a diagnostic and interventional modality.
Current literature supports the use of ultrasound in disaster response as a real-time, portable, safe, reliable, repeatable, easy-to-use, and accurate tool. While both false positives and false negatives were reported in prehospital studies, these values correlate to accepted false positive and negative rates of standard in-hospital point-of-care ultrasound exams. Studies involving austere environments demonstrate the ability to apply ultrasound in extreme conditions and to obtain high-quality images with only modest training and real-time remote guidance. The potential for point-of-care ultrasound in triage and management of mass casualty incidents is there. However, as these studies are heterogeneous and observational in nature, further research is needed as to how to integrate ultrasound into the response and recovery phases.