Life expectancy inequalities in Wales before COVID-19: an exploration of current contributions by age and cause of death and changes between 2002 and 2018.

OBJECTIVES: The COVID-19 pandemic in Wales and the UK has highlighted significant and historic inequalities in health between social groups. To better understand the composition of these inequalities and inform planning after the pandemic, we undertook a decomposition of life expectancy inequalities between the most and least deprived quintiles for men and women by age and cause of death and explored trends between 2002 and 2018. STUDY DESIGN: Statistical decomposition of life expectancy inequalities by age and cause of death using routine population mortality datasets. METHODS: We used routine statistics from the Office for National Statistics for the period 2002-2018 on population and deaths in Wales stratified by age, gender, Welsh Index of Multiple Deprivation (WIMD) 2019 quintile and cause of death, categorised by International Classification of Disease, version 10, code into 15 categories of public health relevance. We aggregated data to 3-year rolling figures to account for low numbers of events in some groups annually. Next, we estimated life expectancy at birth by quintile, gender and period using life table methods. Lastly, we performed a decomposition analysis using the Arriaga method to identify the specific disease categories and ages at which excess deaths occur in more disadvantaged areas to highlight potential areas for action. RESULTS: Life expectancy inequalities between the most and least WIMD quintiles rose for both genders between 2002 and 2018: from 4.69 to 6.02 years for women (an increase of 1.33 years) and from 6.34 to 7.42 years for men (an increase of 1.08 years). Exploratory analysis of these trends suggested that the following were most influential for women: respiratory disease (1.50 years), cancers (1.36 years), circulatory disease (1.35 years) and digestive disease (0.51 years). For men, the gap was driven by circulatory disease (2.01 years), cancers (1.39 years), respiratory disease (1.25 years), digestive disease (0.79 years), drug- and alcohol-related conditions (0.54 years) and external causes (0.54 years). Contributions for women from respiratory disease, cancers, dementia and drug- and alcohol-related conditions appeared to be increasing, while among men, there were rising contributions from respiratory, digestive and circulatory disease. CONCLUSIONS: Life expectancy inequalities in Wales remain wide and have been increasing, particularly among women, with indications of worsening trends since 2010 following the introduction of fiscal austerity. As agencies recover from the pandemic, these findings should be considered alongside any resumption of services in Wales or future health and public policy.

Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs.

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well-defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause-specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.

An assessment of intra- and interobserver agreement of reporting orthopaedic findings on presale radiographs of Thoroughbred yearlings.

REASONS FOR PERFORMING STUDY: Radiography is commonly used in clinical practice but agreement of reporting of radiographically detected orthopaedic findings in horses has rarely been studied. OBJECTIVES: To assess agreement within and between observers for reporting of orthopaedic findings on presale radiographs of Thoroughbred yearlings. STUDY DESIGN: Retrospective analysis of archived radiographs. METHODS: Four veterinary radiology specialists each twice examined 167 sets of radiographs for orthopaedic findings in the fore feet, fore and hind fetlocks, carpi, tarsi and stifles. There were 27 findings analysed for agreement. Kappa statistic (κ), percentage of positive agreement (Ppos) and percentage of negative agreement are reported. RESULTS: An excellent percentage of negative agreement was observed for all findings, with the exception of regular vascular channels of the proximal sesamoid bones. Ppos and κ results were variable. The presence of extra carpal bones, osseous cyst-like lesions of the ulnar carpal bone, sagittal ridge defects of the third metacarpus, fracture of the fore and hind proximal sesamoid bones, regular vascular channels in the hind proximal sesamoids, osteochondrosis lesions of the distal intermediate ridge and/or medial malleoli of the tibia, and osseous cyst-like lesions in the medial femoral condyle was consistently observed with an intra- and interagreement κ≥0.5 and Ppos≥50%. Lucency within the proximal sesamoids consistently had an observed intra- and interagreement κ<0.4 and Ppos<40%. CONCLUSIONS: Observation of orthopaedic findings on yearling repository radiographs showed generally excellent agreement on the absence of findings, but variable agreement on the presence of findings. Agreement was good for larger and easy to categorise radiographic findings. More accurate definitions and training need to be developed to improve agreement within and between observers for orthopaedic findings with poor or fair to good agreement.

Research-intensive cancer care in the NHS in the UK.

In the late 1990 s, in response to poor national cancer survival figures, government monies were invested to enhance recruitment to clinical cancer research. Commencing with England in 2001 and then rolling out across all four countries, a network of clinical cancer research infrastructure was created, the new staff being linked to existing clinical care structures including multi-disciplinary teams. In parallel, a UK-wide co-ordination of cancer research funders driven by the 'virtual' National Cancer Research Institute, combined to create a 'whole-system approach' linking research funders, researchers and NHS clinicians all working to the same ends. Over the next 10 years, recruitment to clinical trials and other well-designed studies, increased 4-fold, reaching 17% of the incident cancer population, the highest national rate world-wide. The additional resources led to more studies opened, and more patients recruited across the country, for all types of cancers and irrespective of additional clinical research staff in some hospitals. In 2006, a co-ordinated decision was made to increasingly focus on randomized trials, leading to increased recruitment, without any fall-off in accrual to non-randomized and observational studies. The National Cancer Research Network has supported large successful trials which are changing clinical practice in many cancers.

Extending the clinical research network approach to all of healthcare.

The development of Clinical Research Networks (CRN) has been central to the work conducted by Health Departments and research funders to promote and support clinical research within the NHS in the UK. In England, the National Institute for Health Research has supported the delivery of clinical research within the NHS primarily through CRN. CRN provide the essential infrastructure within the NHS for the set up and delivery of clinical research within a high-quality peer-reviewed portfolio of studies. The success of the National Cancer Research Network is summarized in Chapter 5. In this chapter progress in five other topics, and more recently in primary care and comprehensively across the NHS, is summarized. In each of the 'topic-specific' networks (Dementias and Neurodegenerative Diseases, Diabetes, Medicines for Children, Mental Health, Stroke) there has been a rapid and substantial increase in portfolios and in the recruitment of patients into studies in these portfolios. The processes and the key success factors are described. The CRN have worked to support research supported by pharmaceutical, biotechnology and medical device companies and there has been substantial progress in improving the speed, cost and delivery of these 'industry' studies. In particular, work to support the increased speed of set up and delivery of industry studies, and to embed this firmly in the NHS, was explored in the North West of England in an Exemplar Programme which showed substantial reductions in study set-up times and improved recruitment into studies and showed how healthcare (NHS) organizations can overcome delays in set up times when they actively manage the process. Seven out of 20 international studies reported that the first patient to be entered anywhere in the world was from the UK. In addition, the CRN have supported research management and governance, workforce development and clinical trials unit collaboration and coordination. International peer reviews of all of the CRN have been positive and resulted in the continuation of the system for a further 5 years in all cases.

Strengthening clinical cancer research in the United Kingdom.

BACKGROUND: In 1999, 270,000 cases of cancer were registered in the United Kingdom, placing a large burden on the NHS. Cancer outcome data in 1999 suggested that UK survival rates were poorer than most other European countries. In the same year, a Department of Health review noted that clinical trials accrual was poor (<3.5% of incident cases) and hypothesised that increasing research activity might improve outcomes and reduce the variability of outcomes across England. Thus, the National Cancer Research Network (NCRN) was established to increase participation in cancer clinical research. METHODS: The NCRN was established in 2001 to provide a robust infrastructure for cancer clinical research and improvements in patient care. Remit of NCRN is to coordinate, support and deliver cancer clinical research through the provision of research support staff across England. The NCRN works closely with similar networks in Scotland, Wales and the Northern Ireland. A key aim of NCRN is to improve the speed of research and this was also assessed by comparing the speed of study delivery of a subset of cancer studies opening before and after NCRN was established. RESULTS: Patient recruitment increased through NCRN, with almost 32,000 (12% of annual incident cases) cancer patients being recruited each year. Study delivery has improved, with more studies meeting the recruitment target - 74% compared with 39% before NCRN was established. CONCLUSION: The coordinated approach to cancer clinical research has demonstrated increased accrual, wide participation and successful trial delivery, which should lead to improved outcomes and care.

Concurrent sialocoele and necrotising sialadenitis in a dog.

A seven-year-old male, entire rottweiler was presented to Murdoch University Veterinary Hospital with a 24 hour history of blindness, chemosis, exophthalmus, pain on opening the mouth and hypersialism. Bilateral mandibular and zygomatic salivary gland enlargement with concurrent bilateral zygomatic salivary gland sialocoeles were identified. The cause of the mandibular salivary gland enlargement was confirmed as necrotising sialadenitis, while the cause of the zygomatic gland enlargement was presumed to be because of a similar disease process. No underlying aetiology was identified. Treatment consisted of supportive management, corticosteroids and paracentesis of the sialocoeles and resulted in resolution of the salivary gland enlargement and the associated clinical signs. This is an unusual presentation of salivary gland disease in the dog with multiple gland involvement and a spectrum of disease processes occurring at the same time.

Childhood overweight and obesity: is the gap closing the wrong way?

BACKGROUND: Obesity is a significant public health issue. Obese children have an increased risk of developing chronic adult diseases. Knowledge of socio-economic distribution trends in childhood overweight/obesity is limited. METHODS: Body mass indices for 3-year-old children resident in three South Wales localities from 1995 to 2005 were derived from the National Community Child Health Database (NCCHD) and examined in relation to residence lower super output area (LSOA) Townsend Material Deprivation Score. RESULTS: Over 11 years, 53-69% of children had height/weight measurements recorded (with little difference observed across deprivation fifths). Amalgamating the data for all 11 years showed no significant association of prevalence with LSOA socio-economic status. Annual trends varied substantially: the most deprived fifth had the lowest proportion on five, and the highest on six, occasions. Linear regression analysis suggested a greater rate of increase of overweight/obesity in children from most-deprived LSOA areas compared with those from least deprived areas (not statistically significant). CONCLUSIONS: Socio-economic difference in overweight/obesity prevalence lessened between 1995 and 2005. Despite annual variation, this apparent closing of the gap has been the result of an increase in overweight/obesity prevalence in children from the most deprived areas who, initially, had a lower prevalence compared with children from least deprived areas, but by 2005, had overtaken them.

Staphylococcus aureus colonization and infection in New York State prisons.

Methicillin-resistant Staphylococcus aureus is increasingly responsible for staphylococcal outbreaks in prison. There is limited information on the source of the outbreak strains, risk factors for infection, and transmission of these strains within a prison. We conducted a survey to determine the prevalence of nasal colonization with S. aureus in 2 New York State prisons. S. aureus isolates from clinical cultures collected from all New York State prisons during a 6-month period were compared with the colonizing strains. Analyses were conducted to determine whether prison-level characteristics were associated with colonization or infection with S. aureus. The colonization rate was 25.5% (124/487); 10.5% of the isolates were methicillin resistant, all were staphylococcal chromosomal cassette (SCC)mec type IV, and 61.5% were Panton Valentine leukocidin (PVL) positive. Surprisingly, 21.6% of the methicillin-susceptible isolates were also PVL positive. Of the clinical isolates, 48.3% were methicillin resistant, with 93.1% of the latter being SCCmec type IV and 48.3% being PVL positive. The predominant clone was USA 300. Prison-level risk factors for infection included the proportion of inmates with drug offenses, the length of inmate stay, and the jail from which inmates originated. This study suggests that both new and long-term inmates act as sources of S. aureus strains, with the more virulent of the latter preferentially being selected as pathogens.

Promoting HCV treatment completion for prison inmates: New York State's hepatitis C continuity program.

This article describes the development of a statewide program providing continuity of hepatitis C virus (HCV) treatment to prisoners upon release to the community. We discussed length of stay as a barrier to treatment with key collaborators; developed protocols, a referral process, and forms; mobilized staff; recruited heath-care facilities to accept referrals; and provided short-term access to HCV medications for inmates upon release. The Hepatitis C Continuity Program, including 70 prisons and 21 health-care facilities, is a resource for as many as 130 inmates eligible to start treatment annually. Health-care facilities provide fairly convenient access to 87.1% of releasees, and 100% offer integrated HCV-human immunodeficiency virus/acquired immunodeficiency syndrome care. As of March 2006, 24 inmates had been enrolled. The program was replicated in the New York City Rikers Island jail. The program is operational statewide, referrals sometimes require priority attention, and data collection and other details are still being addressed.

Accuracy of prediction of canine litter size and gestational age with ultrasound.

Different sonographic criteria have been developed to estimate canine fetal age, including fetal mensuration and assessment of fetal organ development. This retrospective study assessed the accuracy of gestational age and litter size predictions in 76 bitches using one of two techniques. The first method used the differential features of fetal organ development that occur in early and mid pregnancy, based on published tables for beagles. The second method used biparietal head and trunk diameters to predict gestational age based on tables published for late gestational Labrador Retrievers. The accuracy of the two methods was compared and the effect of maternal body weight and litter size evaluated. Litter size and maternal body weight did not affect the accuracy of gestational age prediction. Using a combination of both methods, the overall accuracy of predicting parturition date within 65 +/- 1 day and +/- 2 days was 70.8% and 86.1%, respectively. The correct litter size was predicted in 65% of cases, and in 89.5% of cases for +/- 1 pup. Pearson's correlation between actual litter size and predicted litter size was high (R = 0.957, P < 0.001). The organ development method of predicting gestational age was more accurate than late gestational fetal mensuration (P = 0.019). The optimum time for sonographic estimation of fetal age and litter size is early and mid pregnancy.

Gall bladder torsion and rupture in a dog.

A 6-year-old desexed female German Shepherd dog was referred to the Murdoch University Veterinary Hospital for assessment and management of acute onset vomiting, diarrhoea, polydipsia and lethargy of 2 days duration. Surgical, microbiological and histological findings were consistent with necrotising cholecystitis secondary to gall bladder torsion, resulting in gall bladder rupture and secondary non-septic bile peritonitis. A chronic peritoneopleural perforation resulting from an abdominal cavity foreign body and congenital peritoneopericardial hernia were also present. The dog made a full recovery following cholecystectomy, foreign body removal, repair of the peritoneopleural perforation and peritoneopericardial herniorrhaphy. This is the first recorded case of gall bladder torsion in the dog.

The relationship between orofacial clefts and material deprivation in wales.

OBJECTIVE: This study investigated the relationship between material deprivation and the incidence of orofacial clefts (OFC) in South, West, and Central Wales, U.K. DESIGN AND SETTING: The South, West, and Central Wales Orofacial-Cleft Register served as the primary data source for the study. Data on all children born with an orofacial cleft between 1982 and 2003 were geocoded to one of 844 geographic wards. National census data, similarly geocoded, served as the population denominator. Townsend's index of material deprivation was used to assign wards to one of seven levels of deprivation. This permitted investigation of the association of orofacial clefts with material deprivation. RESULTS: Between 1982 and 2003, there were 831 babies born with an orofacial cleft, equating to 109 clefts per 100,000 live births. The incidence of orofacial clefts ranged from 82 per 100,000 (95% confidence interval [C.I.] 64 to 102 per 100,000) in babies born to mothers residing in the least deprived areas to 127 per 100,000 (95% C.I., 112 to 144 per 100,000) in those living in the most deprived areas, a significant linear trend being apparent (p < .001). A statistically significant risk of 1.55 (95% C.I., 1.18 to 2.04) for orofacial clefts was apparent between most and least deprived septiles of deprivation. CONCLUSIONS: This study provides further evidence of an association between material deprivation and orofacial clefts. Further work is required to elicit the degree to which potential risk factors contribute to this association and to determine how deprivation predisposes to orofacial clefts.

Disseminated cryptococcosis including osteomyelitis in a horse.

A 4-year-old Arab mare was diagnosed with disseminated cryptococcosis, including osteomyelitis of the proximal phalanx of the left hind limb, osteomyelitis with associated soft tissue granuloma of a rib and disseminated, large cryptococcal nodules in the lungs. The lesion in the dorsoproximal aspect of the proximal phalanx had a large area of cortical lysis with spiculated periosteal new bone and extensive soft tissue swelling. The affected rib had a pathological fracture. Cryptococcal osteomyelitis has not been previously reported in horses but should be considered as a differential diagnosis, particularly in endemic regions.

Meticillin-resistant Staphylococcus aureus among US prisoners and military personnel: review and recommendations for future studies.

We reviewed published work examining the prevalence and risk factors for meticillin-resistant Staphylococcus aureus (MRSA) infection in two high-risk groups: prisoners and military enlistees. Significant risk factors for infection included prison occupation, gender, comorbidities, prior skin infection, and previous antibiotic use. Although characteristics such as hygiene, physical contact, and crowding were postulated as risk factors for MRSA infection, there were few epidemiological studies supporting these factors. Most studies identified were retrospective in design and only one study used prospective surveillance for MRSA colonisation among all individuals residing within a single military setting. Our results suggest that there is a high incidence of MRSA infection among individuals in prisons and military settings, but surveys that quantify the prevalence of MRSA colonisation among individuals living within these specialised settings are needed. A thorough examination of MRSA acquisition and transmission patterns in prisons and military settings could help elucidate preventive strategies in other crowded and closed settings.

Cyclooxygenase-2-specific inhibitor improves functional outcomes, provides neuroprotection, and reduces inflammation in a rat model of traumatic brain injury.

OBJECTIVE: Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. METHODS: DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5)H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model. RESULTS: DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3-immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3-immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuroprotective endocannabinoid, in the injured brain. CONCLUSION: These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials.

Interpreting the von Bertalanffy model of somatic growth in fishes: the cost of reproduction.

We develop a model for somatic growth in fishes that explicitly allows for the energy demand imposed by reproduction. We show that the von Bertalanffy (VB) equation provides a good description of somatic growth after maturity, but not before. We show that the parameters of the VB equation are simple functions of age at maturity and reproductive investment. We use this model to show how the energy demands for both growth and reproduction trade off to determine optimal life-history traits. Assuming that both age at maturity and reproductive investment adapt to variations in adult mortality to maximize lifetime offspring production, our model predicts that: (i) the optimal age of maturity is inversely related to adult mortality rate; (ii) the optimal reproductive effort is approximately equal to adult mortality rate. These predictions are consistent with observed variations in the life-history traits of a large sample of iteroparous freshwater fishes.

Spontaneous antenatal resolution of canine hydrops fetalis diagnosed by ultrasound.

A previously unreported syndrome of transient mid-gestational hydrops fetalis identified by ultrasound was diagnosed in 16 litters of 16 different dogs between November 1999 and May 2002. During this study period, a total of 161 canine pregnancies were diagnosed by ultrasound. A 17th litter of eight fetuses developed similar ultrasonographic changes concurrently with maternal systemic mastocytosis and subsequently spontaneously aborted. No pups were born with clinical signs of hydrops fetalis. Fetal resorption in the affected litters was 7/95 (7.4 per cent) and 8/95 (8.4 per cent) aborted. Of the fetuses that survived to term, there were 7/88 (8 per cent) stillbirths. Neonatal mortality rate in the affected litters was 15 per cent (11/73) and the incidence of congenital abnormalities was 7/73 (9.6 per cent). Pugs were significantly (22.8 times) more likely to be affected than other breeds.

Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle.

The clinical safety, use and pharmacokinetics of a new needle-free device for delivery of growth hormone (GH) were compared with those of conventional needle injection devices. In an open-label, randomized, 4-period crossover study, 18 healthy adults received single subcutaneous injections of Genotropin administered by the Genotropin ZipTip needle-free device and by conventional injection. Bioequivalence was established between the devices. In a separate open-label, randomized, multicenter, 2-period crossover study, pediatric patients underwent 2-weeks Genotropin treatment administered by the Genotropin ZipTip and by a fine-gauge needle device (>95% used the Genotropin Pen). In total, 128/133 patients who were treated completed the study. Genotropin ZipTip was well tolerated and >50% of patients found no difference between the devices for all parameters assessed. After study completion, >20% patients preferred to continue using Genotropin ZipTip. Although statistical analyses demonstrated superiority of the Genotropin Pen versus Genotropin ZipTip for bleeding, pain, soreness, and bruising, Genotropin ZipTip was considered to provide a safe and bioequivalent alternative to needle injection.