Clinical characteristics, attendance outcomes and deaths of homeless persons in the emergency department: implications for primary health care and community prevention programmes.

OBJECTIVES: Persons experiencing homelessness (PEH) are known to be often excluded from primary health care and community prevention programmes leading to high use of hospital emergency departments (EDs). This study aimed to identify demographic features, clinical characteristics and attendance outcomes of PEH presenting to ED. STUDY DESIGN: Analysis of routinely collected data set. METHODS: Clinical presentations and drug prescription data of PEH who presented a major ED in the West Midlands region of England from 2014 to 2019 were extracted and analysed using descriptive and inferential statistics. RESULTS: During the study period, 3271 of 596,198 presentations were made by PEH; 74% PEH attendees were male. Drug- and alcohol-related conditions, as well as pain and injury constituted the most frequent reasons for presentation, contributing to over half of all presentations. A significantly higher proportion of males (n = 481, 20.3%) presented with drug and alcohol problems than females (n = 93, 11.2%) (P ≤ 0.001). However, pain was the primary reason for presentation for twice as many female patients (n = 189, 22.8%) compared with males (n = 305, 12.9%) (P < 0.001). Nearly one in five left the ED before being assessed and a total of 39 patients (1.2%) died in the ED and 785 (24.0%) required in-patient admissions to the same hospital. CONCLUSIONS: Drug, alcohol and pain including the need of opioid analgesics constituted the majority of presentations made by PEH in ED. The observed rate of death of PEH in ED is 12 times higher than the general population. A very high proportion of PEH also leave the ED before being treated. Future research should focus on strengthening community interventions, particularly to improve access to those at risk of dual diagnoses of substance misuse and mental health problems. Interventions involving multisector collaborations are needed to improve seamless discharge from ED and minimise repeat attendance. Gender differences in the nature of presentations and ED outcomes needs to be investigated further.

The current status of prophylactic femoral intramedullary nailing for metastatic cancer.

The most common site for cancer to spread is bone. At post-mortem, bony metastases have been found in 70% of patients dying from breast and prostate cancer. Due to the prevalence of cancer, bone metastasis and the associated management represents a huge burden on NHS resources. In patients with metastasis, around 56% of these involve the lower limb long bones. Due to the huge forces placed upon long bones during weight bearing, there is a high risk of fracture through areas of metastasis. It is reported that 23% of pathological fractures occur in the femoral subtrochanteric region. This area is subjected to forces up to four times the body weight, resulting in poor union rate for these fractures, and significant morbidity associated with difficulty in mobilising, and in patient nursing. As cancer treatments improve, the life expectancy in this subgroup of patients is likely to increase. Therefore medium-to-long-term management of these fractures, beyond the palliative, will become essential. We aim to evaluate the current management for metastatic malignant femoral disease, with particular focus on the prophylactic augmentation of diseased femorii using intramedullary nails.

Emergency department syndromic surveillance providing early warning of seasonal respiratory activity in England.

Seasonal respiratory infections place an increased burden on health services annually. We used a sentinel emergency department syndromic surveillance system to understand the factors driving respiratory attendances at emergency departments (EDs) in England. Trends in different respiratory indicators were observed to peak at different points during winter, with further variation observed in the distribution of attendances by age. Multiple linear regression analysis revealed acute respiratory infection and bronchitis/bronchiolitis ED attendances in patients aged 1-4 years were particularly sensitive indicators for increasing respiratory syncytial virus activity. Using near real-time surveillance of respiratory ED attendances may provide early warning of increased winter pressures in EDs, particularly driven by seasonal pathogens. This surveillance may provide additional intelligence about different categories of attendance, highlighting pressures in particular age groups, thereby aiding planning and preparation to respond to acute changes in EDs, and thus the health service in general.

Using an Emergency Department Syndromic Surveillance System to investigate the impact of extreme cold weather events.

This report describes the development of novel syndromic cold weather public health surveillance indicators for use in monitoring the impact of extreme cold weather on attendances at EDs, using data from the 2010-11 and 2011-12 winters. A number of new surveillance indicators were created specifically for the identification and monitoring of cold weather related ED attendances, using the diagnosis codes provided for each attendance in the Emergency Department Syndromic Surveillance System (EDSSS), the first national syndromic surveillance system of its kind in the UK. Using daily weather data for the local area, a time series analysis to test the sensitivity of each indicator to cold weather was undertaken. Diagnosis codes relating to a health outcome with a potential direct link to cold weather were identified and assigned to a number of 'cold weather surveillance indicators'. The time series analyses indicated strong correlations between low temperatures and cold indicators in nearly every case. The strongest fit with temperature was cold related fractures in females, and that of snowfall was cold related fractures in both sexes. Though currently limited to a small number of sentinel EDs, the EDSSS has the ability to give near real-time detail on the magnitude of the impact of weather events. EDSSS cold weather surveillance fits well with the aims of the Cold Weather Plan for England, providing information on those particularly vulnerable to cold related health outcomes severe enough to require emergency care. This timely information aids those responding to and managing the effects on human health, both within the EDs themselves and in the community as a whole.

The impact of thunderstorm asthma on emergency department attendances across London during July 2013.

BACKGROUND: This study illustrates the potential of using emergency department attendance data, routinely accessed as part of a national syndromic surveillance system, to monitor the impact of thunderstorm asthma. METHODS: The Emergency Department Syndromic Surveillance System (EDSSS) routinely monitors anonymised attendance data on a daily basis across a sentinel network of 35 emergency departments. Attendance data for asthma, wheeze and difficulty breathing are analysed on a daily basis. RESULTS: A statistically significant spike in asthma attendances in two EDSSS emergency departments in London was detected on 23 July 2013, coinciding with a series of large violent thunderstorms across southern England. There was also an increase in the reported severity of these attendances. CONCLUSIONS: This preliminary report illustrates the potential of the EDSSS to monitor the impact of thunderstorms on emergency department asthma attendances. Further work will focus on how this system can be used to quantify the impact on emergency departments, thus potentially improving resource planning and also adding to the thunderstorm asthma evidence-base.

Real-time epidemic forecasting for pandemic influenza.

The ongoing worldwide spread of the H5N1 influenza virus in birds has increased concerns of a new human influenza pandemic and a number of surveillance initiatives are planned, or are in place, to monitor the impact of a pandemic in near real-time. Using epidemiological data collected during the early stages of an outbreak, we show how the timing of the maximum prevalence of the pandemic wave, along with its amplitude and duration, might be predicted by fitting a mass-action epidemic model to the surveillance data by standard regression analysis. This method is validated by applying the model to routine data collected in the United Kingdom during the different waves of the previous three pandemics. The success of the method in forecasting historical prevalence suggests that such outbreaks conform reasonably well to the theoretical model, a factor which may be exploited in a future pandemic to update ongoing planning and response.

Partial NSD1 deletions cause 5% of Sotos syndrome and are readily identifiable by multiplex ligation dependent probe amplification.

BACKGROUND: Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions. It is uncertain whether allelic or genetic heterogeneity underlies the residual cases and it has been proposed that other mechanisms, such as 11p15 defects, might be responsible for Sotos cases without NSD1 mutations or 5q35 microdeletions. OBJECTIVE: To develop a multiplex ligation dependent probe amplification (MLPA) assay to screen NSD1 for exonic deletions/duplications. METHODS: Analysis was undertaken of 18 classic Sotos syndrome cases in which NSD1 mutations and 5q35 microdeletions were excluded. Long range polymerase chain reaction (PCR) was used to characterise the mechanism of generation of the partial NSD1 deletions. RESULTS: Eight unique partial NSD1 deletions were identified: exons 1-2 (n = 4), exons 3-5, exons 9-13, exons 19-21, and exon 22. Using long range PCR six of the deletions were confirmed and the precise breakpoints in five cases characterised. This showed that three had arisen through Alu-Alu recombination and two from non-homologous end joining. CONCLUSIONS: MLPA is a robust, inexpensive, simple technique that reliably detects both 5q35 microdeletions and partial NSD1 deletions that together account for approximately 15% of Sotos syndrome.

Maternal uniparental disomy 16 and genetic counseling: new case and survey of published cases.

Uniparental disomy (UPD) is the occurrence of both homologous chromosomes from one parent. Maternal UPD(16) is the most often reported UPD other than UPD(15); almost all cases are associated with confined placental mosaicism (CPM). Most of maternal UPD(16) cases are characterised by intrauterine growth retardation (IUGR) and different congenital malformations. Maternal UPD(16) has therefore been suspected to have clinical effects: however, the lack of uniqueness and specificity of the birth defects observed suggests that the phenotype may be related in parts to placental insufficiency. We report on a new case of maternal UPD(16) associated with low level trisomy 16 mosaicism in placenta and fetus. IUGR was noticed at 19 gestational weeks and the fetus died intrauterine. Apart from different craniofacial dysmorphisms she showed anal atresia. While IUGR is probably associated with trisomy 16 mosaicism, anal atresia is more characteristic for maternal UPD( 16). Considering the features in our patient as well as those in maternal UPD (16) cases from the literature, indications for UPD (16) testing can be defined: They include trisomy 16 mosaicism, IUGR and congenital anomalies (anal atresia, congenital heart defects). However, there is an overlap of clinical signs in mosaic trisomy 16 cases mosaic for maternal UPD(16) as opposed to those mosaic for biparental disomy 16. The management of trisomy 16 pregnancies should not differ from those in which maternal UPD(16) is confirmed. Therefore, a prenatal testing for UPD(16) is not useful, but it should be offered postnatally. The molecular genetic proof of maternal UPD(16) excludes an increased recurrence risk for the family for further pregnancies.

Two components of actin-based retrograde flow in sea urchin coelomocytes.

Sea urchin coelomocytes represent an excellent experimental model system for studying retrograde flow. Their extreme flatness allows for excellent microscopic visualization. Their discoid shape provides a radially symmetric geometry, which simplifies analysis of the flow pattern. Finally, the nonmotile nature of the cells allows for the retrograde flow to be analyzed in the absence of cell translocation. In this study we have begun an analysis of the retrograde flow mechanism by characterizing its kinetic and structural properties. The supramolecular organization of actin and myosin II was investigated using light and electron microscopic methods. Light microscopic immunolocalization was performed with anti-actin and anti-sea urchin egg myosin II antibodies, whereas transmission electron microscopy was performed on platinum replicas of critical point-dried and rotary-shadowed cytoskeletons. Coelomocytes contain a dense cortical actin network, which feeds into an extensive array of radial bundles in the interior. These actin bundles terminate in a perinuclear region, which contains a ring of myosin II bipolar minifilaments. Retrograde flow was arrested either by interfering with actin polymerization or by inhibiting myosin II function, but the pathway by which the flow was blocked was different for the two kinds of inhibitory treatments. Inhibition of actin polymerization with cytochalasin D caused the actin cytoskeleton to separate from the cell margin and undergo a finite retrograde retraction. In contrast, inhibition of myosin II function either with the wide-spectrum protein kinase inhibitor staurosporine or the myosin light chain kinase-specific inhibitor KT5926 stopped flow in the cell center, whereas normal retrograde flow continued at the cell periphery. These differential results suggest that the mechanism of retrograde flow has two, spatially segregated components. We propose a "push-pull" mechanism in which actin polymerization drives flow at the cell periphery, whereas myosin II provides the tension on the actin cytoskeleton necessary for flow in the cell interior.

Severe prenatal growth retardation, dysmorphic features, pigmentary retinopathy, and generalized absence of subcutaneous tissues: a new entity?

We report a girl with severe prenatal and postnatal growth retardation, congenital generalized absence of subcutaneous tissue, and facial and somatic changes with some similarities to Wiedemann-Rautenstrauch syndrome (WRS). However, the patient's condition is sufficiently different from those reported previously to suggest that this patient represents a new syndrome. The abnormalities observed in this patient overlap with those of WRS, Cockayne syndrome, type A (CSA), and osteodysplastic primordial dwarfism type III (OPD III), but also include choanal atresia and pigmentary retinopathy.

Contracting for clinical genetic services: the Welsh model.

In a time of increasing competition for clinical services resources, it is imperative that health professionals actively participate in the commissioning process in order to ensure that established clinical standards are not compromised. Introduction of the NHS reforms in the UK in the early 1990s highlighted the difficulties in contracting for a specialised service such as clinical genetics, especially in the absence of a consensus regarding the contract currency. An average block contract price for each new family referred was introduced in Wales in 1992, and data from the subsequent five years show that this charging system is economically feasible and has the advantages of (1) recognising the contribution to care of non-medical personnel on the genetics team, (2) covering follow up including the counselling of relatives, (3) protecting the service from loss of income owing to non-attendance, and (4) providing a basis for negotiation when new services are being proposed to purchasers. Activity data show that while the majority of conditions incur below average cost, the mean cost is influenced by a small number of autosomal dominant and X linked disorders. The cost risk to the provider for seeing families over an extended period is minimal, as the data establish that family files experience an exponential decrease in activation probability over the early years, but this becomes constant later on. The robustness of the system is dependent on accurate baseline data on referral patterns to the service, recording of activity, and staff costs.

Lateral meningocele syndrome: three new patients and review of the literature.

One female and two male patients with multiple lateral meningoceles are presented. They do not have neurofibromatosis or Marfan syndrome and share findings with the two previously described patients with multiple lateral meningoceles. The original report by Lehman et al. [1977: J Pediatr 90:49-54] was titled "familial osteosclerosis," because osteosclerosis was present in the proposita and her mother; the patient described by Philip et al. [1995: Clin Dysmorphol 4:347-351] also had increased bone density of the skull base and the sutures. Thickened calvaria were present in one of our patients; two had a prominent metopic suture. Other shared findings include multiple lateral meningoceles, Wormian bones, malar hypoplasia, downslanted palpebral fissures, a high narrow palate, and cryptorchidism in males. In addition, our patients showed ligamentous laxity, keloid formation, hypotonia, and developmental delay. A short umbilical cord was noted in two patients. One had a hypoplastic posterior arch of the atlas and an enlarged sella, as reported by Lehman et al. [1977]. Our patients appear to have the same syndrome as previously reported. We suggest it be called "lateral meningocele syndrome," because of this unique finding.

Prenatal cocaine exposure affects the acoustic startle response in adult rat.

This study investigated whether prenatal exposure to cocaine alters reflux excitability in adulthood. Pregnant rats received 30 or 60 mg/kg/day cocaine HCl i.g. during gestational days 8-22. Vehicle-treated control rats were pair-fed/watered to rats receiving 60 mg/kg cocaine. A non-treated control group was also maintained. At parturition, litters from all four groups were surrogate fostered and then weaned at 21 days of age. In adulthood, rats were tested in an acoustic startle response (ASR) apparatus for 120 trials using a 116 dB signal on 2 consecutive days. On Day 2, subjects received a single injection of d-amphetamine sulfate s.c. (1.0 mg/kg) just prior to testing. ASR amplitude and latency were recorded. For average amplitude, significant effects for prenatal treatment were observed. Cocaine-exposed female rats demonstrated decreased ASR amplitude compared to offspring of pair-fed controls during both the initial test Session and following amphetamine administration as well. Overall, amphetamine increased startle. For latency, there were no significant treatment effects or effects of amphetamine administration. However, preplanned comparisons indicated that prenatal cocaine exposure interacted with trial block. Therefore, these data indicate that prenatal cocaine decreased startle amplitude in adults, primarily in females, and that startle-elicited amphetamine responses were dampened as well. The effects on latency indicate that amphetamine does not alter reaction times in prenatal cocaine exposed rats while it does in controls.

A cytogenetic deletion, del(17)(q11.22q21.1), in a patient with sporadic neurofibromatosis type 1 (NF1) associated with dysmorphism and developmental delay.

We report the first visible cytogenetic deletion involving the NF1 gene in a patient with sporadic neurofibromatosis, dysmorphic features, and marked developmental delay. The combined evidence of molecular and cytogenetic techniques based on dosage reduction, hemizygosity for microsatellite markers, high resolution G banding, and FISH analysis, predicts this deletion to be approximately 7 Mb in size. Our findings highlight the importance of conducting a detailed cytogenetic and FISH analysis in patients with NF1 who have additional dysmorphic features or particularly severe learning difficulties.

Adult reactivity in rats exposed to cocaine during two early postnatal periods.

This study investigated whether exposure to cocaine during two periods of postnatal development affects the acoustic startle response (ASR) in adulthood. Female rats received 50 mg/kg/day cocaine HCl or vehicle SC during either postnatal days 1-10 or 11-20. At 60-65 days of age, subjects were ASR tested for 30 min on 2 consecutive days. Overall, ASR was increased on day 1 compared to day 2. Also comparisons between groups within each session and injection schedule showed that subjects exposed to cocaine during postnatal days 1-10 exhibited increased ASR amplitude on the second day of testing compared to controls. No group differences in response latency were observed. Therefore, these data indicate that, for female rats, cocaine alters the development of the pathways involved in modification of the acoustic startle response in a way consistent with a disruption of long-term habituation, but that the critical period for this disruption in females is postnatal days 1-10 and not 11-20.

Twenty-four cases of the EEC syndrome: clinical presentation and management.

Twenty-four cases of EEC syndrome were identified as part of a nationwide study. Ectodermal dysplasia, by study definition, was present in all cases and hair and teeth were universally affected. Nail dysplasia was present in 19 subjects (79%) and the skin was affected in 21 (87%). The presence of hypohidrosis was not noted as a predominant feature in the syndrome and its occurrence appeared to depend on the presence of all other features. Distal limb defects from simple syndactyly to tetramelic cleft hand and foot were identified, including preaxial anomalies. Orofacial clefting was identified in 14 cases (58%) and lacrimal duct anomaly in 21 (87%). Significant clinical problems encountered were chiefly cosmetic or ophthalmological, but conductive deafness and genitourinary problems in some cases required surgical intervention. Altered self-image was also noted in some cases. Multidisciplinary management is necessary with the early involvement of the clinical geneticist. Developmentally, the EEC syndrome and related disorders represent disorders of ectodermal/mesodermal interaction. Candidate regions include 7q21.3, the "ectrodactyly" locus; other candidates include developmental genes implicated in the ectodermal/mesodermal interactive process.