Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality.

BACKGROUND: Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. METHODS: Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. RESULTS: One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. CONCLUSIONS: The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. REGISTRATION: This review was registered on PROSPERO as CRD42020177714 .

Adherence to cardiovascular medication: a review of systematic reviews.

BACKGROUND: Use of cardiovascular medication has increased over time, especially for primary and secondary prevention, with polypharmacy common. METHODS: Review of published systematic reviews of the factors and outcomes associated with adherence to cardiovascular medication using MEDLINE, Embase, CINAHL and PsycINFO databases. Quality was assessed using the AMSTAR tool. RESULTS: Of 789 systematic reviews identified, 45 met the inclusion criteria and passed the quality assessment; 34 focused on factors associated with adherence, and 11 on outcomes. High heterogeneity, both between and within reviews, precluded meta-analysis and so a pooled estimate of adherence levels could not be derived. Adherence was associated with disease factors, therapy factors, healthcare factors, patient factors and social factors, though with some inconsistencies. In total, 91% of reviews addressing outcomes reported that low adherence was associated with poorer clinical and economic endpoints. CONCLUSIONS: Factors from across five key domains relate to non-adherence to cardiovascular medications, and may contribute to poorer clinical outcomes. Interventions to improve adherence should be developed to address modifiable factors and targeted at those at highest risk of non-adherence. Adherence research is highly heterogeneous to-date and efforts to standardize this should be implemented to improve comparability.

Genetic and Biochemical Biomarkers in Canine Glaucoma.

In many health-related fields, there is great interest in the identification of biomarkers that distinguish diseased from healthy individuals. In addition to identifying the diseased state, biomarkers have potential use in predicting disease risk, monitoring disease progression, evaluating treatment efficacy, and informing pathogenesis. This review details the genetic and biochemical markers associated with canine primary glaucoma. While there are numerous molecular markers (biochemical and genetic) associated with glaucoma in dogs, there is no ideal biomarker that allows early diagnosis and/or identification of disease progression. Genetic mutations associated with canine glaucoma include those affecting ADAMTS10, ADAMTS17, Myocilin, Nebulin, COL1A2, RAB22A, and SRBD1. With the exception of Myocilin, there is very limited crossover in genetic biomarkers identified between human and canine glaucomas. Mutations associated with canine glaucoma vary between and within canine breeds, and gene discoveries therefore have limited overall effects as a screening tool in the general canine population. Biochemical markers of glaucoma include indicators of inflammation, oxidative stress, serum autoantibodies, matrix metalloproteinases, tumor necrosis factor-α, and transforming growth factor-ß. These markers include those that indicate an adaptive or protective response, as well as those that reflect the damage arising from oxidative stress.

Anticholinergic medicines in an older primary care population: a cross-sectional analysis of medicines' levels of anticholinergic activity and clinical indications.

WHAT IS KNOWN AND OBJECTIVES: Adverse clinical outcomes have been associated with cumulative anticholinergic burden (to which low-potency as well as high-potency anticholinergic medicines contribute). The clinical indications for which anticholinergic medicines are prescribed (and thus the 'phenotype' of patients with anticholinergic burden) have not been established. We sought to establish the overall prevalence of prescribing of anticholinergic medicines, the prevalence of prescribing of low-, medium- and high-potency anticholinergic medicines, and the clinical indications for which the medicines were prescribed in an older primary care population. METHODS: This was a cross-sectional analysis of a cohort study of Australian early-career general practitioners' (GPs') clinical consultations - the Registrar Clinical Encounters in Training (ReCEnT) study. In ReCEnT, GPs collect detailed data (including medicines prescribed and their clinical indication) for 60 consecutive patients, on up to three occasions 6 months apart. Anticholinergic medicines were categorized as levels 1 (low-potency) to 3 (high-potency) using the Anticholinergic Drug Scale (ADS). RESULTS: During 2010-2014, 879 early-career GPs (across five of Australia's six states) conducted 20 555 consultations with patients aged 65 years or older, representing 35 506 problems/diagnoses. Anticholinergic medicines were prescribed in 10·4% [95% CIs 9·5-10·5] of consultations. Of the total anticholinergic load of prescribed medicines ('community anticholinergic load') 72·7% [95% CIs 71·0-74·3] was contributed by Level 1 medicines, 0·8% [95% CIs 0·5-1·3] by Level 2 medicines and 26·5% [95% CIs 24·8-28·1] by Level 3 medicines. Cardiac (40·0%), Musculoskeletal (16·9%) and Respiratory (10·6%) were the most common indications associated with Level 1 anticholinergic prescription. For Level 2 and 3 medicines (combined data), Psychological (16·1%), Neurological (16·1%), Musculoskeletal (15·7%) and Urological (11·1%) indications were most common. WHAT IS NEW AND CONCLUSION: Anticholinergic medicines are frequently prescribed in Australian general practice, and the majority of the 'community' anticholinergic burden is contributed by 'low'-anticholinergic potency medicines whose anticholinergic effects may be largely 'invisible' to prescribing GPs. Furthermore, the clinical 'phenotype' of the patient with high anticholinergic burden may be very different to common stereotypes (patients with urological, psychological or neurological problems), potentially making recognition of risk of anticholinergic adverse effects additionally problematic for GPs.

Aspirin use and survival after the diagnosis of breast cancer: a population-based cohort study.

BACKGROUND: Aspirin use has been associated with a reduced cancer incidence and fewer deaths from cancer. This study examined whether women with breast cancer prescribed aspirin postdiagnosis had improved survival. METHODS: An observational, population cohort study was undertaken using data linkage of cancer registry, dispensed prescriptions and death records in Tayside, Scotland. All community prescriptions for aspirin in women with breast cancer were extracted and use postdiagnosis for each individual examined using Cox's proportional hazard models. The main outcome measures were all-cause mortality and breast cancer-specific mortality. RESULTS: Four thousand six hundred and twenty-seven patients diagnosed with breast cancer between 1 January 1998 and 31 December 2008 were followed up until 28 February 2010. Median age at diagnosis was 62 (IQR 52-74). One thousand eight hundred and two (39%) deaths were recorded, with 815 (18%) attributed to breast cancer. One thousand and thirty-five (22%) patients were prescribed aspirin postdiagnosis. Such aspirin use was associated with lower risk of all-cause mortality (HR=0.53, 95% CI=0.45-0.63, P<0.001) and breast cancer-specific mortality (HR=0.42, 95% CI=0.31-0.55, P<0.001) after adjusting for age, socioeconomic status, TNM stage, tumour grade, oestrogen receptor status, surgery, radiotherapy, chemotherapy, adjuvant endocrine therapy and aspirin use prediagnosis. CONCLUSIONS: Aspirin use postdiagnosis of breast cancer may reduce both all-cause and breast cancer-specific mortality. Further investigation seeking a causal relationship and which subgroups of patients benefit most await ongoing randomised controlled trials.

The value of high adherence to tamoxifen in women with breast cancer: a community-based cohort study.

BACKGROUND: Low adherence to adjuvant tamoxifen is associated with worse health outcomes but little is known about the cost-effectiveness of high adherence. METHODS: We conducted an economic evaluation using data for all women with incident breast cancer between 1993 and 2000 who were subsequently prescribed tamoxifen in the Tayside region of Scotland. Patient-level, lifetime Markov models evaluated the impact of high vs low adherence to tamoxifen using linked prescribing, cancer registry, clinical cancer audit, hospital discharge and death records. Direct medical costs were estimated for each patient and quality-of-life weights were assigned. Recurrence information was collected by case note review and adherence calculated from prescribing records with low adherence classed below 80%. RESULTS: A total of 354 (28%) patients had a recorded recurrence and 504 (39%) died. Four hundred and seventy-five (38%) patients had low adherence over the treatment period, which was associated with reduced time to recurrence of 52% (P<0.001). Time to other cause mortality was also reduced by 23% (P=0.055) but this was not statistically significant. For an average patient over her lifetime, low adherence was associated with a loss of 1.43 (95% CI: 1.15-1.71) discounted life years or 1.12 (95% CI: 0.91-1.34) discounted quality-adjusted life years (QALYs) and increased discounted medical costs of £5970 (95% CI: £4644-£7372). Assuming a willingness to pay threshold of £25,000 per QALY, the expected value of changing a patient from low to high adherence is £33,897 (95% CI: £28,322-£39,652). CONCLUSION: Patients with low adherence have shorter time to recurrence, increased medical costs and worse quality of life. Interventions that encourage patients to continue taking their treatment on a daily basis for the recommended 5-year period may be highly cost-effective.

Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality.

BACKGROUND: Adjuvant endocrine therapy is recommended for women with oestrogen receptor-positive breast cancer, but many women do not take the medication as directed and they stop treatment before completing the standard 5-year duration. METHODS: This retrospective cohort study conducted between 1993 and 2008 of all women with incident breast cancer, who are residing in the Tayside region of Scotland, examined adherence to prescribed adjuvant tamoxifen or aromatase inhibitors (AIs). Survival analysis examined the effect of adherence on all-cause mortality, breast cancer death and recurrence, using linked prescribing, cancer registry, clinical cancer audit, hospital discharge and death records. RESULTS: A total of 3361 women with breast cancer were followed for a median 4.47 years (interquartile range (IQR)=2.04-8.55). The median overall adherence was 90% (IQR=90-100%), but the annual adherence reduced after a longer period from diagnosis. Low adherence of <80% was associated with poorer survival (hazard ratios=1.20; 95% confidence interval=1.03-1.40, P=0.019). There was no significant difference for low adherence over the treatment period and recurrence, or breast cancer death, but patients with high annual adherence for 5 years had better outcomes than those with 3 or less. CONCLUSION: Low adherence to all adjuvant endocrine therapy for women with breast cancer, whether tamoxifen or AI, increases the risk of death.

Electron shell ionization of atoms with classical, relativistic scattering.

We investigate forward scattering of ionization from neon, argon, and xenon in ultrahigh intensities of 2 × 10(19) W/cm(2). Comparisons between the gases reveal the energy of the outgoing photoelectron determines its momentum, which can be scattered as far forward as 45° from the laser wave vector k(laser) for energies greater than 1 MeV. The shell structure in the atom manifests itself as modulations in the photoelectron yield and the width of the angular distributions. We arrive at an agreement with theory by using an independent electron model for the atom, a dipole approximation for the bound state interaction, and a relativistic, three-dimensional, classical radiation field including the laser magnetic field. The studies provide the atomic physics within plasmas, radiation, and particle acceleration in ultrastrong fields.

Avian pox in crimson rosellas (Platycercus elegans) in southern Australia.

Poxviral infection was identified in a crimson rosella presented to the Australian Wildlife Health Centre (Victoria) in 2002, and from a second crimson rosella in 2008. Both cases were characterized by proliferative lesions on non-feathered skin. Routine histopathology identified intra-lesional epidermal changes consistent with those caused by poxvirus. Electron microscopy confirmed the presence of poxvirus in inclusions in the first case, and genetic analysis of DNA extracted from both cases found an identical viral genome that differs from all other known poxviruses. We conclude that this infection in crimson rosellas is caused by a previously unrecognized avian poxvirus endemic to this region of Australia, and with low virulence.

Mapping cerebellar abiotrophy in Australian Kelpies.

An autosomal recessive form of cerebellar abiotrophy occurs in Australian Kelpie dogs. Clinical signs range from mild ataxia with intention tremor to severe ataxia with seizures. A whole-genome mapping analysis was performed using Affymetrix Canine SNP array v2 on 11 affected and 19 control dogs, but there was no significant association with disease. A homozygosity analysis identified a three megabase region likely to contain the disease mutation. The region spans 29.8-33 Mb on chromosome 3, for which all affected dogs were homozygous for a common haplotype. Microsatellite markers were developed in the candidate region for linkage analysis that resulted in a logarithm of odds score suggestive of linkage. The candidate region contains 29 genes, none of which are known to cause ataxia.

First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.

Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.

Diagnostic accuracy systematic review of rectal bleeding in combination with other symptoms, signs and tests in relation to colorectal cancer.

BACKGROUND: Rectal bleeding is a recognised early symptom of colorectal cancer. This study aimed to assess the diagnostic accuracy of symptoms, signs and diagnostic tests in patients with rectal bleeding in relation to risk of colorectal cancer in primary care. METHODS: Diagnostic accuracy systematic review. Medline (1966 to May 2009), Embase (1988 to May 2009), British Nursing Index (1991 to May 2009) and PsychINFO (1970 to May 2009) were searched. We included cohort studies that assessed the diagnostic utility of rectal bleeding in combination with other symptoms, signs and diagnostic tests in primary care. An eight-point quality assessment tool was produced to assess the quality of included studies. Pooled positive likelihood ratios (PLRs), sensitivities and specificities were calculated. RESULTS: Eight studies incorporating 2323 patients were included. Average weighted prior probability of colorectal cancer was 7.0% (range: 3.3-15.4%, median: 8.1%). Age > or = 60 years (pooled PLR: 2.79, 95% confidence interval (CI) 2.00-3.90), weight loss (pooled PLR: 1.89, 95% CI: 1.03-3.07) and change in bowel habit (pooled PLR: 1.92, 95% CI: 0.54-3.57) raise the probability of colorectal cancer into the range of referral to secondary care but do not conclusively 'rule in' the diagnosis. Presence of severe anaemia has the highest diagnostic value (pooled PLR: 3.67, 95% CI: 1.30-10.35), specificity 0.95 (95% CI: 0.93-0.96), but still only generates a post-test probability of 21.6%. CONCLUSIONS: In patients with rectal bleeding who present to their general practitioner, additional 'red flag' symptoms have modest diagnostic value. These findings have implications in relation to recommendations contained in clinical practice guidelines.

p53 mutation, deprivation and poor prognosis in primary breast cancer.

BACKGROUND: The deprivation gap for breast cancer survival remains unexplained by stage at presentation, treatment, or co-morbidities. We hypothesised that p53 mutation might contribute to the impaired outcome observed in patients from deprived communities. METHODS: p53 mutation status was determined using the Roche Amplichip research test in 246 women with primary breast cancer attending a single cancer centre and related to deprivation, pathology, overall, and disease-free survival. RESULTS: p53 mutation, identified in 64/246 (26%) of cancers, was most common in 10 out of 17 (58.8%) of the lowest (10th) deprivation decile. Those patients with p53 mutation in the 10th decile had a significantly worse disease-free survival of only 20% at 5 years (Kaplan-Meier logrank chi(2)=6.050, P=0.014) and worse overall survival of 24% at 5 years (Kaplan-Meier logrank chi(2)=6.791, P=0.009) than women of deciles 1-9 with p53 mutation (c.f. 56% and 72%, respectively) or patients in the 10th decile with wild-type p53 (no disease relapse or deaths). CONCLUSION: p53 mutation in breast cancer is associated with socio-economic deprivation and may provide a molecular basis, with therapeutic implications, for the poorer outcome in women from deprived communities.

The effect of aerobic exercise on treatment-related acute toxicity in men receiving radical external beam radiotherapy for localised prostate cancer.

We retrospectively analysed acute radiation toxicity data for patients who had participated in a randomised controlled study in our centre in order to assess the impact of aerobic exercise on acute rectal and bladder morbidity during treatment. Data from 65 of 66 patients were analysed: 33 allocated into a control group (standard advice) and 33 into an exercise group (aerobic walking for 30 min at least three times per week) during 4 weeks of external beam radiotherapy; one patient in the exercise group withdrew after randomisation before starting radiotherapy. There was a trend towards less severe acute rectal toxicity in the exercise group with a statistically significant difference in mean toxicity scores over the 4 weeks of radiotherapy (P=0.004), with no significant difference in bladder toxicity scores between the two groups (P=0.123). The lack of an association for severity of bladder toxicity could be attributed to the confounding effect of lower urinary tract symptoms from their prostate cancer. Keeping active and being asked to adhere to a well-defined exercise schedule appears to reduce the severity of rectal toxicity during radiotherapy to the prostate.

Protocol for assessment of the pupillary light reflex in dogs without chemical restraint: preliminary investigation.

OBJECTIVE: To explore the use of a modified pupillometry technique in dogs without chemical restraint. MATERIALS AND METHODS: Following dark adaptation, pupillary light reflexes were assessed in six dogs with sudden acquired retinal degeneration syndrome, in the unaffected eye of eight dogs with unilateral primary glaucoma ("predisposed"), and in 11 healthy dogs. Responses to red, blue and white lights were recorded and relative pupil sizes subsequently determined based on video recordings of each test. RESULTS: Mean testing time was 2.3 minutes (range 1.8 to 3.1 minutes), excluding time for dark adaptation. Baseline pupil size in dogs with sudden acquired retinal degeneration syndrome was greater than in normal and predisposed eyes. Pupil constriction was reduced in predisposed compared to normal and sudden acquired retinal degeneration syndrome eyes when stimulated with high-intensity blue light. Compared to normal eyes, those with sudden acquired retinal degeneration syndrome had reduced pupil constriction when stimulated with low- and high-intensity red light, low-intensity blue light and white light. CLINICAL SIGNIFICANCE: Quantitative measures of pupil function were obtained from healthy and diseased eyes without the need for chemical restraint. Further investigations are warranted to validate the technique and evaluate its use in the management of canine glaucoma.

Cost burden of Clostridioides difficile infection to the health service: A retrospective cohort study in Scotland.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with high healthcare demands and related costs. AIM: To evaluate the healthcare and economic burden of CDI in hospitalized patients with community- (HOCA-CDI) or hospital-associated CDI (HOHA-CDI) in the National Health Service in Scotland. METHODS: A retrospective cohort study was conducted, examining data between August 2010 and July 2013 from four patient-level Scottish datasets, linked to death data. Data examined included prior antimicrobial prescriptions in the community, hospitalizations, length of stay and mortality. Each CDI case was matched to three hospital-based controls on the basis of age, gender, hospital and date of admission. Descriptive economic evaluations were based on bed-day costs for different types of wards. FINDINGS: Overall, 3304 CDI cases were included in the study. CDI was associated with additional median lengths of stay of 7.2 days for HOCA-CDI and 12.0 days for HOHA-CDI compared with their respective, matched controls. The 30-day mortality rate was 6.8% for HOCA-CDI and 12.4% for HOHA-CDI. Overall, recurrence within 90 days of the first CDI episode occurred in 373/2740 (13.6%) survivors. The median additional expenditure for each initial CDI case compared with matched controls was £1713. In the 6 months after the index hospitalization, the cost associated with a CDI case was £5126 higher than for controls. CONCLUSION: Using routinely collected national data, we demonstrated the substantial burden of CDI on healthcare services, including lengthy hospital stays and readmissions, which increased the costs of managing patients with CDI compared with matched controls.

Double-outlet right ventricle in a 10-month-old Friesian filly.

A 10-month-old Friesian filly had a presentation that was consistent with chronic left- and right-sided congestive heart failure. Clinical pathology findings included abnormal haematological and biochemical variables, abnormal blood gas values and increased serum concentration of cardiac troponin I. Echocardiography revealed cardiac chamber dilation and dextropositioning of the aorta. Radiography revealed a generally enlarged heart and pulmonary interstitial infiltration. These findings were supported at necropsy and the diagnosis of double-outlet right ventricle was confirmed. The pathological changes and physiological responses subsequent to double-outlet right ventricle have not previously been described in detail in horses. Clinical progression closely resembles that seen in humans, in whom antemortem diagnosis relies on echocardiography. In horses, complex cardiac disease presents a diagnostic challenge to the clinician. Appropriate therapy must be based on an accurate diagnosis.

A forced-choice preferential looking task for the assessment of vision in dogs: pilot study.

OBJECTIVES: To describe preliminary use of a forced-choice preferential looking task for the clinical assessment of vision in dogs. MATERIALS AND METHODS: The vision of 18 pet dogs was investigated in two separate studies using a forced-choice preferential looking task: multiple observers watched eye, head and body movements on video recordings to identify cues suggesting when a dog had seen the feature of interest. Human observer reliability was determined using eight dogs and computer-generated stimuli. Visual acuity was assessed using computer-generated grating stimuli: in real-time, an observer watched each dog's eye movement patterns and behaviour to decide whether each grating was seen. Stimuli were presented in a step-wise manner and were controlled by the observer. Acuity was estimated as the highest spatial frequency the dog was determined to have seen. RESULTS: Median estimated visual acuity was better at 1 m compared to that at 3 m. Average test time was longer at a 3-m distance than at 1 m. Inter- and intra-observer reliability was better from 1 m than from 3 m. CLINICAL SIGNIFICANCE: Preliminary use of a forced-choice preferential looking task for measurement of visual acuity in dogs has potential use as a clinical tool for the assessment of vision in dogs.

Bovine digital dermatitis in Victoria, Australia.

AIMS: The objectives of this study were to estimate the prevalence of digital dermatitis (DD) in Victoria, Australia, and to investigate which organisms are consistent with typical DD lesions. The prevalence and causative pathogens of DD are not clear yet in Australia and this paper is one of the first to explore these questions in this country. METHODS: Examination and sampling of limbs was undertaken at three knackeries in Victoria, Australia. Limbs were classified as normal (N), active DD-lesion (A), dried or chronic DD-lesion (D) or suspected case of DD (S). A total of 823 cows were examined. Six skin biopsies were taken at each knackery, from which DNA was extracted for diversity profiling. Histochemical staining of samples was performed on eight of the skin biopsies. RESULTS: DD was detected in 29.8% of all cows. The prevalence of DD was significantly higher in dairy cows (32.2%) than in beef cows (10.8%). The differential abundance of Treponema-species was significantly increased in dried lesions, compared with the normal skin biopsies. Actinobacteria, Proteobacteria, Firmicutes and Tenericutes were found to be significantly different in abundance in the DD lesions compared with normal skin biopsies. Silver staining of samples showed only mild inflammation and in two samples organisms with morphology consistent with Spirochaetes were detected. CONCLUSIONS: The calculated prevalence indicates that DD is present in Victoria, Australia. The results of diversity profiling showed that the presence of Treponema-species was significantly different between the samples of DD lesions and normal skin.

Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer.

Increasing duration of tamoxifen therapy improves survival in women with breast cancer but the impact of adherence to tamoxifen on mortality is unclear. This study investigated whether women prescribed tamoxifen after surgery for breast cancer adhered to their prescription and whether adherence influenced survival. A retrospective cohort study of all women with incident breast cancer in the Tayside region of Scotland between 1993 and 2002 was linked to encashed prescription records to calculate adherence to tamoxifen. Survival analysis was used to determine the effect of adherence on all-cause mortality. In all 2080 patients formed the study cohort with 1633 (79%) prescribed tamoxifen. The median duration of use was 2.42 years (IQR=1.04-4.89 years). Longer duration was associated with better survival but this varied over time. The hazard ratio for mortality in relation to duration at 2.4 years was 0.85, 95% CI=0.83-0.87. Median adherence to tamoxifen was 93% (interquartile range=84-100%). Adherence <80% was associated with poorer survival, hazard ratio 1.10, 95% CI=1.001-1.21. Persistence with tamoxifen was modest with only 49% continuing therapy for 5 years of those followed up for 5 years or more. Increased duration of tamoxifen reduces the risk of death, although one in two women do not complete the recommended 5-year course of treatment. A significant proportion of women have low adherence to tamoxifen and are at increased risk of death.