Preliminary indications of the burden of COVID-19 among people who inject drugs in England and Northern Ireland and the impact on access to health and harm reduction services.

OBJECTIVE: The aim of the study was to describe the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on people who inject drugs (PWID) in England, Wales and Northern Ireland. STUDY DESIGN: This is a cross-sectional Unlinked Anonymous Monitoring (UAM) Survey of PWID. METHODS: People who had ever injected psychoactive drugs were recruited to the UAM Survey by specialist drug/alcohol services in England, Wales and Northern Ireland. From June 2020, in addition to providing a dried blood spot sample and completing the UAM behavioural questionnaire, participants were asked to complete an enhanced coronavirus disease 2019 (COVID-19) questionnaire. Preliminary data are presented to the end of October and were compared with data from the 2019 UAM Survey, where possible. RESULTS: Between June and October, 288 PWID were recruited from England and Northern Ireland. One in nine (11%; 29/260) PWID reported testing positive for SARS-CoV-2 or experiencing COVID-19 symptoms. Fifteen percent (26/169) reported injecting more frequently in 2020 than in 2019; cocaine injection in the preceding four weeks increased from 17% (242/1456) to 25% (33/130). One in five PWID (19%; 35/188) reported difficulties in accessing HIV and hepatitis testing, and one in four (26%; 47/179) reported difficulties in accessing equipment for safer injecting. CONCLUSIONS: Our preliminary findings suggest that PWID have experienced negative impacts on health, behaviours and access to essential harm reduction, testing and treatment services owing to the COVID-19 pandemic. Continued monitoring through surveillance and research is needed to understand the subsequent impact of COVID-19 on blood-borne virus transmission in this population and on health inequalities.

New horizons in comprehensive geriatric assessment.

In this article, we discuss the emergence of new models for delivery of comprehensive geriatric assessment (CGA) in the acute hospital setting. CGA is the core technology of Geriatric Medicine and for hospital inpatients it improves key outcomes such as survival, time spent at home and institutionalisation. Traditionally It is delivered by specialised multidisciplinary teams, often in dedicated wards, but in recent years has begun to be taken up and developed quite early in the admission process (at the 'front door'), across traditional ward boundaries and in specialty settings such as surgical and pre-operative care, and oncology. We have scanned recent literature, including observational studies of service evaluations, and service descriptions presented as abstracts of conference presentations to provide an overview of an emerging landscape of innovation and development in CGA services for hospital inpatients.

Comparing primary and secondary health-care use between diagnostic routes before a colorectal cancer diagnosis: cohort study using linked data.

BACKGROUND: Survival in cancer patients diagnosed following emergency presentations is poorer than those diagnosed through other routes. To identify points for intervention to improve survival, a better understanding of patients' primary and secondary health-care use before diagnosis is needed. Our aim was to compare colorectal cancer patients' health-care use by diagnostic route. METHODS: Cohort study of colorectal cancers using linked primary and secondary care and cancer registry data (2009-2011) from four London boroughs. The prevalence of all and relevant GP consultations and rates of primary and secondary care use up to 21 months before diagnosis were compared across diagnostic routes (emergency, GP-referred and consultant/other). RESULTS: The data set comprised 943 colorectal cancers with 24% diagnosed through emergency routes. Most (84%) emergency patients saw their GP 6 months before diagnosis but their symptom profile was distinct; fewer had symptoms meeting urgent referral criteria than GP-referred patients. Compared with GP-referred, emergency patients used primary care less (IRR: 0.85 (95% CI 0.78-0.93)) and urgent care more frequently (IRR: 1.56 (95% CI 1.12; 2.17)). CONCLUSIONS: Distinct patterns of health-care use in patients diagnosed through emergency routes were identified in this cohort. Such analyses using linked data can inform strategies for improving early diagnosis of colorectal cancer.

Hospital activity and cost incurred because of unregistered patients in England: considerations for current and new commissioners.

BACKGROUND: Commissioners are responsible for providing health care for defined geographical areas. A lack of comprehensive national and local information on health needs of unregistered populations makes health service planning difficult. METHODS: A cross-sectional study using Hospital Episode Statistics to quantify the level of inpatient and outpatient activity, and associated cost by patients not registered in primary care in English NHS hospitals. Unregistered patients were defined as those without a valid GP registration, prisoners, military personnel, asylum seekers/immigrants and the homeless. RESULTS: Unregistered patients accounted for 99 615 inpatient admissions and 370 504 outpatient attendances in 2009/10, at a total cost of £242 m. Mental health accounted for 30% of all inpatient costs. The majority of unregistered patients were male and aged 20-39 years. There were high levels of activity and cost in urban local authorities (LAs) (Birmingham and London) and LAs with links to military services (Salisbury, Richmondshire, Southampton). A high total inpatient cost was attributed to trauma, general medicine and mental health specialties. A high total outpatient cost was attributed to genitourinary medicine and trauma specialties. CONCLUSIONS: Health care use by unregistered populations is an important consideration for resource allocation and planning health care services at national and local levels.

Area level impacts on emergency hospital admissions of the integrated care and support pioneer programme in England: difference-in-differences analysis.

OBJECTIVE: To examine whether any differential change in emergency admissions could be attributed to integrated care by comparing pioneer and non-pioneer populations from a pre-pioneer baseline period (April 2010 to March 2013) over two follow-up periods: to 2014/2015 and to 2015/2016. DESIGN: Difference-in-differences analysis of emergency hospital admissions from English Hospital Episode Statistics. SETTING: Local authorities in England classified as either pioneer or non-pioneer. PARTICIPANTS: Emergency admissions to all NHS hospitals in England with local authority determined by area of residence of the patient. INTERVENTION: Wave 1 of the integrated care and support pioneer programme announced in November 2013. PRIMARY OUTCOME MEASURE: Change in hospital emergency admissions. RESULTS: The increase in the pioneer emergency admission rate from baseline to 2014/2015 was smaller at 1.93% and significantly different from that of the non-pioneers at 4.84% (p=0.0379). The increase in the pioneer emergency admission rate from baseline to 2015/2016 was again smaller than for the non-pioneers but the difference was not statistically significant (p=0.1879). CONCLUSIONS: It is ambitious to expect unequivocal changes in a high level and indirect indicator of health and social care integration such as emergency hospital admissions to arise as a result of the changes in local health and social care provision across organisations brought about by the pioneers in their early years. We should treat any sign that the pioneers have had such an impact with caution. Nevertheless, there does seem to be an indication from the current analysis that there were some changes in hospital use associated with the first year of pioneer status that are worthy of further exploration.

The European Virus Archive goes global: A growing resource for research.

The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry. Within three years, it developed from a consortium of nine European laboratories to encompass associated partners in Africa, Russia, China, Turkey, Germany and Italy. In 2014, the H2020 Research and Innovation Framework Programme (INFRAS projects) provided support for the transformation of the EVA from a European to a global organization (EVAg). The EVAg now operates as a non-profit consortium, with 26 partners and 20 associated partners from 21 EU and non-EU countries. In this paper, we outline the structure, management and goals of the EVAg, to bring to the attention of researchers the wealth of products it can provide and to illustrate how end-users can gain access to these resources. Organisations or individuals who would like to be considered as contributors are invited to contact the EVAg coordinator, Jean-Louis Romette, at jean-louis.romette@univmed.fr.

Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome.

The most common sex chromosome aneuploidy, Klinefelter syndrome (KS), is associated with primary gonadal failure and increased morbidity and mortality from cardiometabolic disorders in adulthood. Children with KS also have a high prevalence of metabolic syndrome (MetS) features. To assess the relationship of gonadal and cardiometabolic function in children with KS, we evaluated serum hormones [gonadotropins, inhibin B (INHB), anti-mullerian hormone (AMH), total testosterone (TT)], and features of MetS (waist circumference, fasting lipid panel, fasting blood glucose (FBG), and blood pressure) in 93 pre-pubertal boys with KS age 4-12 years (mean 7.7 ± 2.5 years). The cohort was grouped by age and tanner stage, and biomarkers were compared to normal ranges. A total of 80% of this pre-pubertal cohort had ≥1 feature of metabolic syndrome (MetS) and 11% had ≥3 features of MetS. Risk of MetS was independent of age and body mass index. Sertoli cell dysfunction was common with 18% having an INHB below the normal range. A low INHB was associated with higher FBG, triglycerides, LDL, and lower HDL (p < 0.05). An INHB <50 ng/dL yielded a sensitivity of 83% and a specificity of 79% for having ≥3 features of MetS. INHB and AMH positively correlated with each other (p < 0.001), and high AMH was protective of MetS. TT was below the lower limit of normal in 49% of subjects, with mean values significantly lower than expected (3.3 ng/dL vs. 4.9 ng/dL, p < 0.0001), however, no convincing relationship between TT and MetS was seen. In conclusion, gonadal and cardiometabolic dysfunction are prevalent in pre-pubertal boys with KS. Although the relationship of testosterone deficiency and MetS is well-known, this study is the first to report an association between impaired Sertoli cell function and cardiometabolic risk.

The oxidation of adrenaline and noradrenaline by the two forms of monoamine oxidase from human and rat brain.

The selective monoamine oxidase inhibitors clorgyline and (?)-deprenyl were used to study the distribution of monoamine oxidase-A and -B (MAO-A, MAO-B) activities towards (?)-noradrenaline and (+),(?)-adrenaline in homogenates from seven different regions of human brain. The activities towards 5-hydroxytryptamine and 2-phenethylamine, which are essentially specific substrates for the A- and B-forms, respectively, under the conditions used in this work, were also determined. Noradreanline and adrenaline were substrates for both forms of the enzyme in all regions studied. The total MAO activity was found to be highest in the hypothalamus and lowest in the cerebellar cortex. Use of the selective MAO inhibitors clorgyline and (?)-deprenyl also showed adrenaline and noradrenaline to be substrates for both forms of the enzyme in rat brain. In human cerebral cortex and rat brain the two forms were found to have similar K(m)-values and maximum velocities towards adrenaline. These values for the two forms were also found to be similar in human cerebral cortex when noradrenaline was used as the substrate. In contrast MAO-A showed a significantly lower K(m) and a higher maximum velocity towards noradrenaline in rat brain. These results suggest that the rat may not provide a close model of the human for studies on the effects of MAO inhibitors on brain noradrenaline metabolism.

Health authority commissioning for quality in contraception services.

OBJECTIVE: To compare the commissioning of contraception services by London health authorities with accepted models of good practice. DESIGN: Combined interview and postal surveys of all health authorities and National Health Service (NHS) trusts responsible for running family planning clinics in the Greater London area. MAIN OUTCOME MEASURES: Health authority commissioning was assessed on the presence of four key elements of good practice--strategies, coordination, service specifications, and quality standards in contracts--by monitoring activity and quality. RESULTS: Less than half the health authorities surveyed had written strategies or service specifications for contraception services. Arrangements for coordination of services were limited and monitoring was underdeveloped. CONCLUSION: The process of commissioning services for contraception seems to be relatively underdeveloped despite the importance of health problems associated with unplanned pregnancy in London. These findings raise questions about the capacity of health authorities to improve the quality of these services through the commissioning process.

Evidence for validity of a health status measure in assessing short term outcomes of cholecystectomy.

OBJECTIVE: To assess the validity of the Nottingham health profile (NHP) as an indicator of short term outcome of cholecystectomy. DESIGN: Prospective assessment of outcome. SETTING: One teaching hospital. Patients--161 consecutive patients admitted for cholecystectomy between January 1989 and September 1990. MAIN MEASURES: Patients' reported symptoms and self assessed NHP scores before cholecystectomy and at follow up at three and 12 months (76 patients); assessment before admission (19). RESULTS: Complete data were obtained preoperatively and at three months' follow up from 154 patients; seven did not respond to the follow up questionnaire. 76/84(90%) patients in the study 12 months or more answered the 12 month follow up questionnaire; eight did not respond. Significant changes in score before and at three months after the operation were observed for four of the six dimensions: energy (35.34 v 19.53, p < 0.0001), pain (27.38 v 9.8, p < 0.0001), sleep (26.99 v 17.51, p = 0.0002), and emotional reactions (16.12 v 7.56, p = 0.001). The mean scores for 76 patients followed up at three and 12 months showed little subsequent change. Scores in readmitted patients were all significantly higher, suggesting poor health. Patients with five reported symptoms had significantly worse scores for all dimensions. Scores were similar before cholecystectomy whether the questionnaire was completed before or after admission. CONCLUSION: The NHP is an appropriate tool for monitoring changes in health after cholecystectomy.

Assessing the outcomes of total knee replacement.

The past few years have seen a growth of interest in outcome measurement in a variety of settings including audit, health care management and commissioning - besides the traditional applications in research work. This paper reports on a study of the outcomes of total knee replacement in an acute hospital where the outcomes were studied as part of an audit process. The outcome measures used included clinical and symptomatic measures as well as generic health status scales. The initial study in one hospital was expanded to include a number of others in the same region and a comparative database of outcomes developed. Examples of the results are shown. The technical measures using knee scores and general health status measure show significant improvement from pre-operatively to 3 months later. This improvement was maintained up to the 1-year follow-up on both measures. Although the information systems for collecting and measuring outcomes has been successful, the ability of such measures to lead to behavioural change has been limited. The problems in using outcome measures are discussed in particular in the context of an audit within hospitals, and for purchasing agencies.

Cross sectional study of primary care groups in London: association of measures of socioeconomic and health status with hospital admission rates.

OBJECTIVES: To calculate socioeconomic and health status measures for the primary care groups in London and to examine the association between these measures and hospital admission rates. DESIGN: Cross sectional study. SETTING: 66 primary care groups in London, total list size 8.0 million people. MAIN OUTCOME MEASURES: Elective and emergency standardised hospital admission ratios; standardised admission rates for diabetes and asthma. RESULTS: Standardised hospital admission ratios varied from 74 to 116 for total admissions and from 50 to 124 for emergency admissions. Directly standardised admission rates for asthma varied from 152 to 801 per 100 000 (mean 364) and for diabetes from 235 to 1034 per 100 000 (mean 538). There were large differences in the mortality, socioeconomic, and general practice characteristics of the primary care groups. Hospital admission rates were significantly correlated with many of the measures of chronic illness and deprivation. The strongest correlations were with disability living allowance (R=0.64 for total admissions and R=0.62 for emergency admissions, P<0.0001). Practice characteristics were less strongly associated with hospital admission rates. CONCLUSIONS: It is feasible to produce a range of socioeconomic, health status, and practice measures for primary care groups for use in needs assessment and in planning and monitoring health services. These measures show that primary care groups have highly variable patient and practice characteristics and that hospital admission rates are associated with chronic illness and deprivation. These variations will need to be taken into account when assessing performance.

Safety and efficacy of oxandrolone in growth hormone-treated girls with Turner syndrome: evidence from recent studies and recommendations for use.

There has been no consensus regarding the efficacy and safety of oxandrolone (Ox) in addition to growth hormone (GH) in girls with Turner syndrome (TS), the optimal age of starting this treatment, or the optimal dose. This collaborative venture between Dutch, UK and US centers is intended to give a summary of the data from three recently published randomized, placebo-controlled, double-blind studies on the effects of Ox. The published papers from these studies were reviewed within the group of authors to reach consensus about the recommendations. The addition of Ox to GH treatment leads to an increase in adult height, on average 2.3­4.6 cm. If Ox dosages<0.06 mg/kg/day are used, side effects are modest. The most relevant safety concerns are virilization(including clitoromegaly and voice deepening) and a transient delay of breast development. We advise monitoring signs of virilization breast development and possibly blood lipids during Ox treatment, in addition to regular follow-up assessments for TS. In girls with TS who are severely short for age, in whom very short adult stature is anticipated,or in whom the growth rate is modest despite good compliance with GH, adjunctive treatment with Ox at a dosage of 0.03­0.05 mg/kg/day starting from the age of 8­10 years onward scan be considered.

Effect of a home-based end-of-life nursing service on hospital use at the end of life and place of death: a study using administrative data and matched controls.

OBJECTIVE: To assess the effect of routinely delivered home-based end-of-life care on hospital use at the end of life and place of death. DESIGN: Retrospective analysis using matched controls and administrative data. SETTING: Community-based care in England. PARTICIPANTS: 29,538 people aged over 18 who received Marie Curie nursing support compared with 29,538 controls individually matched on variables including: age, socioeconomic deprivation, prior hospital use, number of chronic conditions and prior diagnostic history. INTERVENTION: Home-based end-of-life nursing care delivered by the Marie Curie Nursing Service (MCNS), compared with end-of-life care available to those who did not receive MCNS care. MAIN OUTCOME MEASURES: Proportion of people who died at home; numbers of emergency and elective inpatient admissions, outpatient attendances and attendances at emergency departments in the period until death; and notional costs of hospital care. RESULTS: Intervention patients were significantly more likely to die at home and less likely to die in hospital than matched controls (unadjusted OR 6.16, 95% CI 5.94 to 6.38, p<0.001). Hospital activity was significantly lower among intervention than matched control patients (emergency admissions: 0.14 vs 0.44 admissions per person, p<0.001) and average costs across all hospital services were lower (unadjusted average costs per person, £610 (intervention patients) vs £1750 (matched controls), p<0.001). Greater activity and cost differences were seen in those patients who had been receiving home nursing for longer. CONCLUSIONS: Home-based end-of-life care offers the potential to reduce demand for acute hospital care and increase the number of people able to die at home.

Generalized neuromuscular hypoplasia, reduced smooth muscle myosin and altered gut motility in the klotho model of premature aging.

BACKGROUND: Gastrointestinal symptoms, particularly constipation, increase with aging, but their underlying mechanisms are poorly understood due to lack of experimental models. Previously we established the progeric klotho mouse as a model of aging-associated anorexia and gastric dysmotility. We also detected reduced fecal output in these animals; therefore, the aim of this study was to investigate in vivo function and cellular make-up of the small intestinal and colonic neuromuscular apparatus. METHODS: Klotho expression was studied by RT-PCR and immunohistochemistry. Motility was assessed by dye transit and bead expulsion. Smooth muscle and neuron-specific gene expression was studied by Western immunoblotting. Interstitial cells of Cajal (ICC) and precursors were analyzed by flow cytometry, confocal microscopy, and three-dimensional reconstruction. HuC/D(+) myenteric neurons were enumerated by fluorescent microscopy. KEY RESULTS: Klotho protein was detected in neurons, smooth muscle cells, and some ICC classes. Small intestinal transit was slower but whole-gut transit of klotho mice was accelerated due to faster colonic transit and shorter intestinal lengths, apparent only after weaning. Fecal water content remained normal despite reduced output. Smooth muscle myosin expression was reduced. ICC, ICC precursors, as well as nitrergic and cholinergic neurons maintained their normal proportions in the shorter intestines. CONCLUSIONS & INFERENCES: Progeric klotho mice express less contractile proteins and develop generalized intestinal neuromuscular hypoplasia mainly arising from stunted postweaning growth. As reduced fecal output in these mice occurs in the presence of accelerated colonic and whole-gut transit, it likely reflects reduced food intake rather than intestinal dysmotility.