COVID-19 vaccine safety in Scotland - background rates of adverse events of special interest.

OBJECTIVES: Mass COVID-19 vaccination commenced in December 2020 in Scotland. Monitoring vaccine safety relies on accurate background incidence rates (IRs) for health outcomes potentially associated with vaccination. This study aimed to quantify IRs in Scotland of adverse events of special interest (AESI) potentially associated with COVID-19 vaccination. STUDY DESIGN AND METHODS: IRs and 95% confidence intervals (CIs) for 36 AESI were calculated retrospectively for the pre-COVID-19 pandemic period (01 January 2015-31 December 2019) and the COVID-19 pandemic period (01 April 2020-30 November 2020), with age-sex stratification, and separately by calendar month and year. Incident cases were determined using International Classification of Diseases-10th Revision (ICD-10)-coded hospitalisations. RESULTS: Prepandemic population-wide IRs ranged from 0.4 (0.3-0.5 CIs) cases per 100,000 person-years (PYRS) for neuromyelitis optica to 478.4 (475.8-481.0 CIs) cases per 100,000 PYRS for acute renal failure. Pandemic population-wide IRs ranged from 0.3 (0.2-0.5 CIs) cases per 100,000 PYRS for Kawasaki disease to 483.4 (473.2-493.7 CIs) cases per 100,000 PYRS for acute coronary syndrome. All AESI IRs varied by age and sex. Ten AESI (acute coronary syndrome, acute myocardial infarction, angina pectoris, heart failure, multiple sclerosis, polyneuropathies and peripheral neuropathies, respiratory failure, rheumatoid arthritis and polyarthritis, seizures and vasculitis) had lower pandemic than prepandemic period IRs overall. Only deep vein thrombosis and pulmonary embolism had a higher pandemic IR. CONCLUSION: Lower pandemic IRs likely resulted from reduced health-seeking behaviours and healthcare provision. Higher IRs may be associated with SARS-CoV-2 infections. AESI IRs will facilitate future vaccine safety studies in Scotland.

Depth-dependent changes in cartilage T2 under compressive strain: a 7T MRI study on human knee cartilage.

OBJECTIVE: To assess the potential of using ΔT2 as an indirect index of cartilage strain by quantifying the relationship between local in situ compressive strain and ΔT2 through the full depth of human tibial and femoral articular cartilage. DESIGN: Osteochondral samples (n = 4) of human tibial and femoral cartilage were harvested from cadavers and imaged in a Bruker 7T research MRI scanner under increasing displacement-controlled compressive strains. T2 was calculated for 3D double echo steady state (DESS) image volumes at each strain level. A decaying exponential model estimated local, depth-dependent strains. Strained image volumes were non-linearly warped back to their unloaded configurations and ΔT2 was calculated by image subtraction. Linear modeling assessed local relationships between strain and ΔT2. RESULTS: Bulk average tibial T2 was 13.2 ms for unstrained cartilage and ranged from 13.0 to 13.1 ms under strain; femoral T2 was 14.0 ms for unstrained cartilage and ranged from 13.5 to 14.8 ms under strain. Local ΔT2 in strained cartilage varied with depth. Linear modeling revealed significant correlations between in situ strain and ΔT2 for both tibial and femoral cartilage; correlation coefficients were higher for tibial cartilage. CONCLUSIONS: Changes in bulk average T2 are unsuitable as a quantitative surrogate measure of cartilage strain because bulk averaging masks important local variations. High-resolution measures of local ΔT2 have potential value as a surrogate for strain; however, their value is limited until we fully understand the influence of factors like age, joint surface and degeneration on the strain vs T2 relationship.

Type 2 diabetes, socioeconomic status and risk of cancer in Scotland 2001-2007.

AIMS/HYPOTHESIS: The objective of this study was to use Scottish national data to assess the influence of type 2 diabetes on the risk of cancer at 16 different sites, while specifically investigating the role of confounding by socioeconomic status in the diabetes-cancer relationship. METHODS: All people in Scotland aged 55-79 years diagnosed with any of the cancers of interest during the period 2001-2007 were identified and classified by the presence/absence of co-morbid type 2 diabetes. The influence of diabetes on cancer risk for each site was assessed via Poisson regression, initially with adjustment for age only, then adjusted for both age and socioeconomic status. RESULTS: There were 4,285 incident cancers in people with type 2 diabetes. RR for any cancers (adjusted for age only) was 1.11 (95% CI 1.05, 1.17) for men and 1.33 (1.28, 1.40) for women. Corresponding values after additional adjustment for socioeconomic status were 1.10 (1.04, 1.15) and 1.31 (1.25, 1.38), respectively. RRs for individual cancer sites varied markedly. CONCLUSIONS/INTERPRETATION: Socioeconomic status was found to have little influence on the association between type 2 diabetes and cancer.

Risk of cancer following primary total hip replacement or primary resurfacing arthroplasty of the hip: a retrospective cohort study in Scotland.

BACKGROUND: Release and dispersion of particles arising from corrosion and wear of total hip arthroplasty (THA) components has raised concerns about a possible increased risk of cancer. Concerns have been heightened by a recent revival in the use of metal-on-metal (MoM) hip prostheses. METHODS: From a linked database of hospital discharge, cancer registration, and mortality records, we selected a cohort of patients who underwent primary THA (1990-2009) or primary resurfacing arthroplasty (mainly 2000-2009) in Scotland, with follow-up to the end of 2010. Available operation codes did not enable us to distinguish MoM THAs. Indirectly standardised incidence ratios (SIRs) were calculated for selected cancers with standardisation for age, sex, deprivation, and calendar period. RESULTS: The study cohort included 71 990 patients yielding 547 001 person-years at risk (PYAR) and 13 946 cancers diagnosed during follow-up. For the total period of observation combined, the risks of all cancers (SIR: 1.05; 95% CI: confidence interval 1.04-1.07), prostate cancer (SIR: 1.07; 95% CI: 1.01-1.14), and multiple myeloma (SIR: 1.22; 95% CI: 1.06-1.41) were increased. These modest increases in risk emerged in the context of effectively multiple tests of statistical significance, and may reflect inadequate adjustment for confounding factors. For 1317 patients undergoing primary resurfacing arthroplasty between 2000 and 2009 (PYAR=5698), the SIR for all cancers (n=39) was 1.23 (95% CI: 0.87-1.68). CONCLUSION: In the context of previous research, these results do not suggest a major cause for concern. However, the duration of follow-up of patients receiving recently introduced, new-generation MoM prostheses is too short to rule out a genuinely increased risk of cancer entirely.

Moving from a universal to targeted child health programme: which children receive enhanced care? A population-based study using routinely available data.

BACKGROUND: There is a current emphasis on 'progressive universal' delivery of the UK child health programme, with a core universal service complemented by enhanced support provided according to need. In Scotland, a three-category indicator of need, the 'Health Plan Indicator' (HPI) is used to identify children requiring enhanced support from the child health programme to facilitate this. METHODS: Routine child health programme and hospital delivery records for a cohort of 36 871 Scottish children were used to explore the factors associated with being identified as requiring enhanced child health programme support using multilevel logistic regression modelling. RESULTS: The following factors were all independently associated with an increased likelihood of being assessed as requiring enhanced support: (i) deprivation; (ii) young maternal age, maternal smoking and drug misuse; (iii) a previous stillbirth; (iv) prematurity; (v) being small for gestational age; (vi) no breastfeeding, admission to a special care baby unit; and (vii) medical, social or developmental concerns about the baby. There was a tendency for children living in areas with higher Health Visitor staffing levels to be more likely to be assessed as requiring enhanced support but this effect was not statistically significant. There was significant residual variation between areas in the likelihood of children being assessed as requiring enhanced support. DISCUSSION: This study suggests Health Visitors take a complex range of factors into account when assessing which children require enhanced support from the child health programme. Health Visitors' workload may influence the likelihood of them identifying children as requiring enhanced support but this requires further clarification. There are clear differences between areas in allocation of the different HPI categories. Further work is required to explore the relationship between being identified as in need of enhanced support, the care actually provided to children, and their outcomes.

Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel.

A polymorphic CAG repeat was identified in the human alpha 1A voltage-dependent calcium channel subunit. To test the hypothesis that expansion of this CAG repeat could be the cause of an inherited progressive ataxia, we genotyped a large number of unrelated controls and ataxia patients. Eight unrelated patients with late onset ataxia had alleles with larger repeat numbers (21-27) compared to the number of repeats (4-16) in 475 non-ataxia individuals. Analysis of the repeat length in families of the affected individuals revealed that the expansion segregated with the phenotype in every patient. We identified six isoforms of the human alpha 1A calcium channel subunit. The CAG repeat is within the open reading frame and is predicted to encode glutamine in three of the isoforms. We conclude that a small polyglutamine expansion in the human alpha 1A calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6.

Public health priority setting on a national scale: The Scottish experience.

Objectives: Scotland has the lowest life expectancy in Western Europe and significant health inequalities. A national review of public health in 2015 found that there was a lack of coherent action across organisational boundaries, inhibiting progress. This paper describes a rapid (four-month) systematic approach to prioritisation of Scotland's public health challenges, which was evidence-based, transparent and made use of significant stakeholder engagement. Study design: Cross-sectional survey of stakeholders in deliberative meetings. Methods: An independent Expert Advisory Group (EAG) was formed to develop a typology of public health priorities, a long-list of potential priorities and ranking criteria. Deliberative stakeholder events were held at which the criteria were refined and priorities scored by participants from a wide range of stakeholder organisations. Results: The proposed typology identified three types of public health priorities: risk factors, social factors and system factors; medically defined disease entities were not used deliberately, to facilitate broad stakeholder participation. Fifteen criteria were identified to help identify priority issues, based on the scope of their burden, amenability to change, and multi-stakeholder preferences. Six public health priorities were selected by the EAG based on stakeholder scoring of a long-list against these criteria. Conclusion: Prioritisation is important in modern public health but it is challenging due to limited data availability, lack of agreed evidence on effectiveness and efficiency of interventions, and divergent stakeholder views. The Scottish experience nevertheless shows that useful public health priorities can be agreed upon by a wide range of stakeholders through a transparent, participatory and logical process.

Characteristics of patients dying within 30 days of diagnosis of breast or colorectal cancer in Scotland, 2003-2007.

BACKGROUND: Recent research has shown that most of the excess risk of death following breast and colorectal cancer in England compared with Norway and Sweden occurs in older age groups during the first year, and especially in the first month of follow-up. The aim of this study was to explore the characteristics of patients dying within 30 days of being diagnosed with one of these cancers in Scotland during 2003-2007. METHODS: Anonymised cancer registry records linked to hospital discharge and death records were extracted. The study population was divided into patients who died within 30 days of diagnosis (cases) and those who survived beyond this threshold (controls). Differences in patient-, tumour-, and health service-related characteristics were assessed using the χ(2)-test and logistic regression. RESULTS: Patients dying within 30 days were more likely to be elderly and to have experienced emergency admission to non-surgical specialities. Their tumours were less likely to have been verified microscopically, but they appeared more likely to be of high grade and advanced in stage. A substantial number of patients died from causes other than their cancer. CONCLUSION: These results suggest that early mortality after a diagnosis of breast or colorectal cancer may be partly due to comorbidity and lifestyle factors, as well as due to more advanced disease. Further research is required to determine the precise explanation for these findings and, in particular, if any potentially avoidable factors such as delays in presentation, referral, or diagnosis exist.

Improving the view of Scotland's health: the impact of a public health observatory upon health improvement policy, action and monitoring in a devolved nation.

The Scottish Public Health Observatory (ScotPHO) is a collaboration of the observatory sections/functions of several organizations. It operates within a small country, part of the UK, with devolved legislative and executive powers in health and in many areas relating to wider social determinants of health. The short-term impact of ScotPHO on health improvement action, policy and monitoring is described. A key factor in ScotPHO's impact is the directness of its contact with Scottish government policy and analysis leadership. The context and organization of ScotPHO differentiates it from other PHOs in the UK and Ireland, but many of the health and information challenges faced are similar and the Association of Public Health Observatories enables experience and expertise to be shared.

What if cancer survival in Britain were the same as in Europe: how many deaths are avoidable?

OBJECTIVE: To estimate the number of deaths among cancer patients diagnosed in Great Britain that would be avoidable within 5 years of diagnosis if the mean (or highest) survival in Europe for patients diagnosed during 1985-1989, 1990-1994 and 1995-1999 were achieved. DESIGN: Five-year relative survival for cancers in Great Britain compared with that from other countries in the EUROCARE-2, -3 and -4 studies. Calculation of excess deaths (those more than expected from mortality in the general population) that would be avoidable among cancer patients in Britain if relative survival were the same as in Europe. SETTING: Great Britain (England, Wales, Scotland) and 13 other European countries. SUBJECTS: 2.8 million adults diagnosed in Britain with 1 of 39 cancers during 1985-1989 (followed up to 1994), 1990-1994 (followed up to 1999) and 1995-1999 (followed up to 2003). MAIN OUTCOME MEASURE: Annual number of avoidable deaths within 5 years of diagnosis. Percentage of the excess (cancer-related) deaths among cancer patients that would be avoidable. RESULTS: Compared with the mean European 5-year relative survival, the largest numbers of avoidable deaths for patients diagnosed during 1985-1989 were for cancers of the breast (about 18% of the excess mortality from this cancer, 7541 deaths), prostate (14%, 4285), colon (9%, 4090), stomach (8%, 3483) and lung (2%, 3548). For 1990-1994, the largest numbers of avoidable deaths were for cancers of the prostate (20%, 7335), breast (15%, 6165), colon (9%, 4376), stomach (9%, 3672), lung (2%, 3735) and kidney (22%, 2644). For 1995-1999, most of the avoidable deaths were for cancers of the prostate (17%, 5758), breast (15%, 5475), lung (3%, 4923), colon (10%, 4295), stomach (9%, 3137) and kidney (21%, 2686).Overall, some 6600-7500 premature deaths would have been avoided each year among cancer patients diagnosed in Britain during 1985-1999 if the mean survival in Europe had been achieved. This represents 6-7% of cancer-related mortality. Compared with the highest European survival, avoidable premature mortality among cancer patients fell from about 12 800 deaths a year (12.2% of cancer-related mortality) to about 11 400 deaths a year (10.6%) over the same period.A large component of the avoidable mortality is due to prostate cancer: excluding this cancer from comparison with the European mean survival reduces the annual number of avoidable deaths by 1000-1500, and the percentage of excess mortality by up to 1%. Compared with the highest survival, the annual number of avoidable deaths would be 1500-2000 fewer, and 1-2% lower as a percentage of excess mortality, but the overall trend in avoidable premature mortality among cancer patients would be similar, falling from 11.4% (1985-1989) to 10.3% (1990-1994) and 9.7% for those diagnosed during 1995-1999.For several cancers, survival in Britain was slightly higher than the mean survival in Europe; this represented some 110-180 premature deaths avoided each year during the period 1985-2003. CONCLUSIONS: Avoidable premature mortality among cancer patients diagnosed in Britain during 1985-1999 has represented 6-7% of cancer-related mortality compared with the mean survival in Europe. Compared with the highest levels of survival in Europe, the reduction from 12.2% to 10.6% of cancer-related mortality reflects small but steady progress over the period 1985-2003.

Idiopathic venous thromboembolic disease is associated with a poorer prognosis from subsequent malignancy.

METHODS: We carried out a retrospective study of prognosis in Scottish patients diagnosed with cancer within 5 years after a venous thromboembolism (VTE). RESULTS AND CONCLUSIONS: Prognosis was significantly poorer if a VTE occurred up to 2 years before cancer diagnosis, most notably if the cancer was diagnosed in the 6 months after a VTE.

Induced Preference Improves Offspring Fitness in a Phytopathogen Vector.

In the Asian citrus psyllid (Diaphorina citri Kuwayama), learning facilitates host recognition and mate preference; however, it is unclear whether induced female oviposition preference occurs in this species. We investigated the influence of natal host experience on adult oviposition preference when reared on either 'Valencia' orange (Citrus x sinesis) or orange jasmine (Murraya paniculata). Psyllids reared on 'Valencia' orange preferred 'Valencia' orange as an oviposition host compared with orange jasmine, whereas there was no difference in oviposition between the two hosts in orange jasmine reared psyllids. Nymphs transferred from 'Valencia' orange to orange jasmine were smaller in adult size and required more time for development. These findings were reversed in orange jasmine reared psyllids, which increased in size and displayed shorter development times when transferred from orange jasmine to 'Valencia' orange. However, mortality increased in nymphs transferred to the non-natal host species in both treatment groups compared with nymphs transferred to the same host. These results indicate an association between host plant preference and performance in this species. Maternal host experience appeared to influence the oviposition preference in this species. Juvenile psyllid performance appeared negatively affected by orange jasmine plants such that fitness was reduced, suggesting benefits for maternal host fidelity in those insects not acclimated to feeding on orange jasmine. Induced oviposition preference may provide an important mechanism of adaptive plasticity in D. citri reproductive strategies, allowing females to discriminate among potential host species in favor of those to which her offspring are best adapted.

Incidence of oral and oropharyngeal cancer in United Kingdom (1990-1999) -- recent trends and regional variation.

This study aimed to determine whether the incidence of oral cancer is continuing to rise in the UK and if this varies geographically. A descriptive epidemiological study of oral cancer incidence in 12 UK cancer registries (1990-1999) was undertaken. Poisson regression models were employed to assess trends. There were 32,852 oral cancer cases registered (1990-1999). Statistically significant increases in incidence of 18% and 30% were seen in males and females respectively (p<0.01). The trend was observed in younger (<45 years) and older (45+ years) age groups (p<0.01) with 3.5% and 2.4% average annual increases respectively. These increases were consistent for the majority of regions in the older group. For the younger group the increases in incidence were more rapid and differed geographically. Incidence remains higher in men than women, in older compared with younger groups, and in northern regions. These findings provide evidence of a continuing increase in the burden of oral cancer across the UK.

Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group.

The natural history of hereditary and BRCA1- and BRCA2-associated epithelial ovarian cancer may differ from that of sporadic disease. The purpose of this study was to compare the clinical characteristics of BRCA1- and BRCA2-associated hereditary ovarian cancer, hereditary ovarian cancer with no identified BRCA1/2 mutation, and ovarian cancer in population-based controls. BRCA1 and BRCA2 mutation testing was carried out on index cases from 119 families with site-specific epithelial ovarian cancer or breast-ovarian cancer. We estimated overall survival in 151 patients from 57 BRCA1 and BRCA2 mutation families and compared it with that in 119 patients from 62 families in which a BRCA1/2 mutation was not identified. We compared clinical outcome and data on tumor histopathology, grade, and stage. We also compared survival in familial epithelial ovarian cancer, whether or not a mutation was identified, with that of an age-matched set of population control cases. Overall survival at 5 years was 21% (95% confidence interval, 14-28) in cases from BRCA1 mutation families, 25% (8-42) in BRCA2 mutation families, and 19% (12-26) in families with no identified mutation (P = 0.91). Survival in familial ovarian cancer cases as a whole was significantly worse than for population controls (P = 0.005). In the familial cases, we found no differences in histopathological type, grade, or stage according to mutation status. Compared to population control cases, mucinous tumors occurred less frequently in the familial cases (2 versus 12%, P<0.001), and a greater proportion of the familial cases presented with advanced disease (83% stage III/IV versus 56%; P = 0.001). We have shown that survival in familial ovarian cancer cases is worse than that in sporadic cases, whether or not a BRCA1/2 mutation was identified, perhaps reflecting a difference in biology analogous to that observed in breast cancer.

Operative treatment of ulnar impaction syndrome: a systematic review.

This article critically and systematically reviews the surgical treatments for ulnar impaction syndrome. Three types of treatments currently exist: arthroscopic wafer procedure, open wafer procedure, and ulna shortening osteotomy. A total of 36 articles were included from searching the electronic databases PubMed MEDLINE, Ovid MEDLINE, and Ovid EMBASE. Studies were evaluated for quality using the Modified Detsky Score. Of these, 14 articles had a Modified Detsky Score of 6/10 or higher. Satisfaction rates were 100% for arthroscopic wafer procedure, 89% for open wafer procedure, and 84% for ulna shortening osteotomy. The percentage of participants reporting an excellent or good outcome was 82% for arthroscopic wafer procedure, 87% for open wafer procedure, and 76% for ulna shortening osteotomy. In conclusion, available evidence shows that arthroscopic wafer procedure and open wafer procedure may be viable alternatives to the more popular ulna shortening osteotomy, but clinical superiority is yet to be established. Future research should focus on prospective cohort methods and should report participant outcomes using validated scoring methods.

Acetylcholinesterase activity in CSF in schizophrenia, depression, Alzheimer's disease and normals.

Acetylcholinesterase (AChE) activity and protein were measured in the CSF of patients with Alzheimer's disease, depression, schizophrenia with and without tardive dyskinesia, and control subjects. AChE activity was assayed by a radioenzymatic method involving the direct extraction of hydrolyzed 3H-acetate into a toluene-based scintillation fluid followed by liquid scintillation spectrometry. AChE activity was proportional to the amount of CSF protein. Greater than 90% of AChE activity in CSF could be inhibited by 10(-3) M eserine. In addition, activity remained stable despite repeated freeze-thawing in an acetone-dry ice bath. Age was found to be positively correlated with CSF protein and AChE activity expressed per volume CSF, but not with AChE measured per milligram protein. No differences between diagnostic groups were found on either measure of AChE when the extraneous factors of age and CSF protein concentrations were controlled, nor were any differences found between groups for CSF protein when age was controlled.

Hereditary neuropathy with liability to pressure palsies is not a major cause of idiopathic carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome is a debilitating neuropathy affecting millions of individuals. Although there are published reports of familial associations of carpal tunnel syndrome, the molecular mechanisms are unknown. OBJECTIVE: To determine the prevalence and potential role of the chromosome 17 microdeletion associated with hereditary neuropathy with liability to pressure palsies in patients diagnosed as having carpal tunnel syndrome. DESIGN: Prospective study. PATIENTS AND METHODS: Since hereditary neuropathy with liability to pressure palsies may present as carpal tunnel syndrome, we evaluated 50 patients with idiopathic carpal tunnel syndrome for hereditary neuropathy with liability to pressure palsies. RESULTS: No hereditary neuropathy with liability to pressure palsies deletions were detected. CONCLUSION: Molecular genetic testing for hereditary neuropathy with liability to pressure palsies in patients with idiopathic carpal tunnel syndrome is of limited value.

Forewarned is forearmed--benefits of preparatory information on video cassette for patients receiving chemotherapy or radiotherapy--a randomised controlled trial.

A series of UK and European audits have revealed that a high proportion of patients remain dissatisfied with the information they received following a diagnosis of cancer. Additional educational aids are often required to facilitate the consent process, and our previous work showed a high level of acceptability for video-directed information for this purpose. In this study a multidisciplinary team of health professionals worked with patients, a documentary film company and experienced television personalities to produce an information film. The aim of this study was to assess the benefits of receiving a cassette to take home following the first consultation and this was evaluated in a randomised multicentre controlled study among 220 patients receiving chemotherapy or radiotherapy over a 6-month period. There was a significant correlation between satisfaction and reduced treatment-related anxiety overall. In the video group, the mean Hospital Anxiety and Depression (HAD) anxiety score was significantly lower during treatment compared with the non-video group (4.6+/-3.7 (range: 0-18) versus 7.4+/-5.2 (range: 0-20), Chi square test P=0.001). Likewise, the mean HAD depression scores were also significantly lower in the patients prepared for the side-effects of treatment with the video (2.9+/-2.9 (range: 0-13) versus 5.3+/-4.7 (range: 0-21) Chi square test P=0.001). 81% felt the video was helpful, only 5% of patients felt this extra information was worrying. Well designed video cassettes should be regarded as a useful additional information strategy, within routine oncology practice.