A feasibility study of microwave therapy for precancerous actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a common premalignant skin lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Microwave therapy is an established cancer treatment and has been used for plantar viral warts. OBJECTIVES: To evaluate the efficacy and feasibility of microwave as a treatment for AK. METHODS: Stage I was a dose-setting study, in which seven participants had the dielectric properties of 12 thick and 22 thin AKs assessed for optimization of the microwave dose used for treatment in Stage II. Stage II was a randomized, internally controlled trial evaluating 179 AKs in 11 patients (93 treated, 86 untreated controls) on the scalp/forehead or dorsal hand. Participants received one treatment initially and a repeat treatment to unresolved AKs at week 4. The response was assessed at six visits over 4 months. The primary outcome was partial or complete resolution of the treated AKs. RESULTS: A significantly higher proportion of treated AK areas responded than untreated (90% vs. 15%; P < 0·001). Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting 'a few seconds only'). Adverse effects were minimal (erythema, n = 6; flaking, n = 3; itch, n = 3). All participants who would chose microwave therapy over their current treatment cited the shorter discomfort period. CONCLUSIONS: Microwave therapy is a portable, safe and effective treatment for AK. An easy-to-deliver, acceptable therapy for AK is attractive as a prevention strategy. While these results are promising, a larger randomized controlled trial is needed against an effective comparator to confirm clinical efficacy and patient acceptability. What is already known about this topic? Actinic keratoses (AKs) are common precancerous skin lesions. Successful treatment of AK can prevent cutaneous squamous cell carcinoma (cSCC). Most topical therapies for AK require repeated application over weeks and drive local skin inflammation, leading to poor compliance. An easy-to-deliver and effective treatment for AK, suitable for use in primary care, could reduce cSCC. What does this study add? Microwave therapy is a feasible, effective treatment for AK. Ninety per cent of treated AKs showed full or partial resolution at 120 days post-treatment. Microwave therapy was painful, but the pain was short-lived (seconds) and this short discomfort period was cited as the main reason that microwave was preferred to their current treatment.

Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription: a primary care data linkage study.

BACKGROUND: Opioid prescribing is increasing worldwide with associated increases in misuse and other harms. We studied variations in national opioid prescription rates, indicators of prescribing quality, co-prescribing of benzodiazepines and relationship with pain severity in Scotland. METHODS: Electronic linkages of opioid prescribing in Scotland were determined from: (i) national data from Information Services Division, NHS Scotland (2003-2012); and (ii) individual data from Generation Scotland: Scottish Family Health Study. Descriptive analyses were conducted on national data, multilevel modelling to examine factors associated with variations in prescribing rates. χ2 tests examined associations between individual pain severity and opioid prescriptions. RESULTS: The number of strong opioid prescriptions more than doubled from 474 385 in 2003 to 1 036 446 in 2012, and weak opioid prescribing increased from 3 261 547 to 4 852 583. In Scotland, 938 674 individuals were prescribed an opioid in 2012 (18% of the population). Patients in the most deprived areas were 3.5 times more likely to receive a strong opioid than patients in the least deprived. There was significant variation in prescribing rates between geographical areas, with much of this explained by deprivation. Of women aged 25-40 yr prescribed a strong opioid, 40% were also prescribed a benzodiazepine. There was significant association between pain severity and receipt of opioid prescription. Over 50% of people reporting severe pain were not prescribed an opioid analgesic. CONCLUSIONS: We found opioid prescribing in primary care to be common and increasing in Scotland, particularly for severe pain. Co-prescribing of opioids and benzodiazepines was common.

NSAID-exacerbated respiratory disease: a meta-analysis evaluating prevalence, mean provocative dose of aspirin and increased asthma morbidity.

BACKGROUND: The prevalence and mean provocative dose of oral aspirin (MPDA) triggering respiratory reactions in people with asthma have been inconsistently reported, and the relationship between NSAID-exacerbated respiratory disease (NERD) and asthma morbidity was less well quantified. METHODS: A systematic review was performed by identifying studies diagnosing NERD using blinded, placebo-controlled oral provocation challenge tests (OPCTs) or by self-reported history in people with asthma. Data were extracted, and effect estimates for changes in respiratory function, MPDA and asthma morbidity were pooled using random-effects meta-analysis. RESULTS: The prevalence of NERD in adults with asthma was 9.0% (95% CI 6-12%) using OPCTs and 9.9% (95% CI 9.4-10.5%) using self-reported history from questionnaires. The MPDA in adults with NERD was 85.8 mg (95% CI 73.9-97.6). In people with NERD, the risk of: uncontrolled asthma was increased twofold (RR 1.96 (95% CI 1.25-3.07)); severe asthma and asthma attacks was increased by 60% (RR 1.58 (95% CI 1.15-2.16) and RR 1.59 (95% CI 1.21-2.09), respectively); emergency room visits was increased by 80% (RR 1.79 (95% CI 1.29-2.49)); and asthma hospitalization was increased by 40% (RR 1.37 (95% CI 1.12-1.67)) compared to people with NSAID-tolerant asthma. CONCLUSIONS: Respiratory reactions triggered by oral aspirin in people with asthma are relatively common. At the population level, the prevalence of NERD was similar when measured using appropriately conducted OPCTs or by self-reported history. On average, respiratory reactions were triggered by clinically relevant doses of oral aspirin. Asthma morbidity was significantly increased in people with NERD who potentially require more intensive monitoring and follow-up.

Does a history of depression actually mediate smoking-related pain? Findings from a cross-sectional general population-based study.

BACKGROUND: Smokers report more pain and worse functioning. The evidence from pain clinics suggests that depression affects this relationship: The association between smoking and chronic pain is weakened when controlling for depression. This study explored the relationship between smoking, pain and depression in a large general population-based cohort (Generation Scotland: Scottish Family Health Study). METHODS: Chronic pain measures (intensity, disability), self-reported smoking status and a history of major depressive disorder (MDD) were analysed. A multivariate analysis of covariance determined whether smoking status was associated with both pain measures and a history of depressive illness. Using a statistical mediation model any mediating effect of depression on the relationship between smoking and chronic pain was sought. RESULTS: Of all 24,024 participants, 30% (n = 7162) reported any chronic pain. Within this chronic pain group, 16% (n = 1158) had a history of MDD; 7108 had valid smoking data: 20% (n = 1408) were current smokers, 33% (n = 2351) former and 47% (n = 3349) never smokers. Current smokers demonstrated higher pain intensity and pain-related disability scores compared with former and non-smokers (p < 0.001 for all analyses). From the mediation model, the effect on pain intensity decreased (p < 0.001), indicating that the relationship between smoking and a history of depression contributes significantly to the effect of smoking on pain intensity. When applied to smoking-related pain disability, there was no mediation effect. CONCLUSIONS: In contrast to smokers treated in pain clinics, a history of MDD mediated the relationship between smoking and pain intensity, but not pain-related disability in smokers in the community.

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.

Use of aspirin post-diagnosis in a cohort of patients with colorectal cancer and its association with all-cause and colorectal cancer specific mortality.

OBJECTIVE: Aspirin is associated with a reduced risk of developing colorectal cancer. This study examined whether patients with colorectal cancer prescribed aspirin had improved survival. DESIGN: An observational population cohort study was undertaken using data linkage of cancer registry, dispensed prescriptions and death certificate records in Tayside, Scotland. All community prescribed aspirin pre- and post-diagnosis was extracted and periods of aspirin use post-diagnosis for each individual were analysed using Cox proportional hazard models. Main outcome measures were all-cause and colorectal mortality from death certificates. RESULTS: Two thousand nine hundred ninety patients were identified with colorectal cancer between 1st January 1997 and 30th December 2006 and followed up until 28th February 2010. Median age at diagnosis was 73 (interquartile range [IQR] 65-80) with 52% male. One thousand nine hundred ninety-eight (67%) deaths were recorded with 1021 (34%) attributed to colorectal cancer. One thousand three hundred forty (45%) patients used aspirin at some stage of the study period. Aspirin use post-diagnosis was associated with lower risk of all cause mortality (hazard ratio [HR]=0.67, 95% confidence interval [CI]=0.57-0.79, p<0.001) and colorectal cancer specific mortality after allowing for age, Dukes' stage, gender, socio-economic status and aspirin use pre-diagnosis. Increasing age and stage at diagnosis were associated with increased risk, with more affluent patients at reduced risk. CONCLUSIONS: Our study suggests that aspirin use post-diagnosis of colorectal cancer may reduce both all cause and colorectal cancer specific mortality. However further work is required to ensure this is a causal relationship and to identify whether it is best used in specific groups of patients.

Prevalence estimates of diagnosed viral hepatitis B, liver condition outcomes and hospitalization costs: a population record-linkage study in Tayside, Scotland.

We estimated prevalence and incidence of liver condition outcomes, and costs to the health service of diagnosed hepatitis B virus (HBV) in Tayside, UK. HBV patients were identified from electronic virology data between 1989 and 2003. The health resource costs of HBV for surface antigen-positive (HBsAg+) patients and HBV (HBsAg+ or immune, i.e. recovered) patients were calculated. A total of 633 patients had HBV (275 HBsAg+), and were more likely to be male (62% vs. 48%), older (mean age 42.6 vs. 39 . 2 years) and deprived than the general population. The prevalence of immune individuals increased steadily. Post-HBV diagnosis, 24% of immune and 13% of HBsAg+ patients were diagnosed with a liver condition. The median cost per immune patient (£3023) was greater than per HBsAg+ patient (£1498) (P=0.02). While increasing prevalence of immune HBV patients highlights an increase in screening and treatment, the costs associated with this group are high.

Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs.

AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p = 3 × 10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.

Resonant quantum transitions in trapped antihydrogen atoms.

The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and--by comparison with measurements on its antimatter counterpart, antihydrogen--the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.

Integration of e-learning resources into a medical school curriculum.

BACKGROUND: E-learning has the potential to make important contributions to medical education, but there has been limited study of a blended approach in which the digital resources are introduced alongside traditional teaching methods such as lectures. METHODS: We describe the successful embedding of an e-learning resource into 3 of the 5 weeks of cardiovascular system teaching for 164 first-year medical students by providing scheduled slots in the timetables. A questionnaire completed by the students at the end of the 5 weeks had a response rate of 66%. Students varied in how they made use of the resource, some systematically working through it and others browsing and studying sections felt to be personally most relevant. RESULTS: Almost all (96%) rated the e-learning resources as probably or definitely of value: they particularly valued interactive activities, animations, video demonstrations, video clips of experts and self-assessment exercises. Graduate students had a significantly more favourable assessment of the e-learning resources than their undergraduate colleagues, while female students felt the value in supporting existing learning opportunities more strongly than male students. CONCLUSIONS: It should not be assumed that all students will choose to use an e-learning resource in the same way and instructional design should enable alternative approaches. The sequence in which the e-learning resource is used in relation to the other learning opportunities, such as lectures and PBL group discussions, may be important and merits further consideration. The experiences reported in this study provide encouragement and pointers for others engaged in the integration of e-learning in their curriculum.

The natural history of treated and untreated primary hyperparathyroidism: the parathyroid epidemiology and audit research study.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder with the majority of cases being mild and untreated. AIM: To provide an update on the natural history of treated and untreated PHPT. DESIGN: Retrospective population-based observational study. METHODS: From 1997 to 2006, a well-defined cohort of PHPT patients was established in Tayside, Scotland. Subsequent cohorts of 'mild untreated' and 'surgically treated' PHPT patients were selected for the present study. Their serum calcium (S-Ca) and PTH concentrations were followed until September 2009. Surgical outcomes were evaluated using hospital admission data. RESULTS: A total of 904 'mild untreated' patients were identified (median follow-up=4.7 years), with a baseline median S-Ca of 2.62 mmol/l. A general decreased trend was observed in the S-Ca concentration for up to 12 years but an increasing trend in PTH (P<0.001 in both instances). Disease progression, defined as an increase in S-Ca concentration, was observed in 121 patients (13.4%). Twenty-six (2.9%) patients had undergone surgery during the subsequent follow-up period. Baseline age and PTH concentration were the only significant risk factors for disease progression. In comparison, there were 200 'surgically treated' patients (median follow-up=5.8 years). S-Ca was normalised after surgery, in 196 patients (98%). Hospital admissions for renal complications were reduced after surgery. In conclusion, most untreated patients with mild PHPT had no progression of S-Ca but approximately 15% did show some evidence of progression. Parathyroidectomy, with a high success rate, normalized the S-Ca in patients with PHPT.

Do managed clinical networks improve quality of diabetes care? Evidence from a retrospective mixed methods evaluation.

PROBLEM: System-wide improvement of chronic disease care is challenging because it requires collaboration and communication across organisational and professional boundaries. Managed clinical networks are one potential solution, but there is little evidence of their effectiveness. DESIGN AND SETTING: Retrospective, mixed-methods evaluation of the form and impact of quality improvement in the Tayside Diabetes Managed Clinical Network (MCN) 1998-2005. STRATEGIES FOR CHANGE: Progressive implementation of multiple quality improvement strategies predominately directed at individuals and clinical teams (guideline development and dissemination, education, clinical audit, encouragement of multidisciplinary team working, task redesign). Information technology played an important role in supporting QI activity, but participants identified it as facilitative rather than delivering QI by itself. More important was achieving widespread clinical engagement through persuasion and appeal to shared professional values by clinical leaders. EFFECTS OF CHANGE: Simple process measures such as glycated haemoglobin measurement rapidly improved. More complex process measures such as eye screening improved more slowly, and were more dependent on redesign of the care pathway. Improvement was greater for type 2 than type 1 diabetes. Significant shifts of care for type 2 diabetes into primary care were achieved, but were harder to achieve without additional resources. LESSONS LEARNT: Delivering better care to whole populations across organisational and professional boundaries required sustained work over long periods, and at all levels of the system of care. Past network focus on clinical collaboration has been effective at improving clinical process and outcome, and the network is now prioritising work with managers and patients to support future redesign.

A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell's palsy: the BELLS study.

OBJECTIVE: To determine whether oral prednisolone or aciclovir, used separately or in combination, early in the course of Bell's palsy, improves the chances of recovery at 3 and 9 months. DESIGN: A 2 x 2 factorial randomised double-blind trial. Patients were randomly assigned to treatment by an automated telephone service using a permuted block randomisation technique with block sizes of four or eight, and no stratification. SETTING: Mainland Scotland, with referrals mainly from general practice to 17 hospital trial sites. PARTICIPANTS: Adults (aged 16 years or older) with unilateral facial nerve weakness of no identifiable cause presenting to primary care, the emergency department or NHS24 within 72 hours of symptom onset. INTERVENTIONS: Patients were randomised to receive active preparations or placebo for 10 days: (1) prednisolone (50 mg per day, 2 x 25-mg capsules) and aciclovir (2000 mg per day, 5 x 400-mg capsules); (2) prednisolone and placebo (lactose, indistinguishable); (3) aciclovir and placebo; and (4) placebo and placebo. OUTCOME MEASURES: The primary outcome was recovery of facial function assessed by the House-Brackmann scale. Secondary outcomes included health status, pain, self-perceived appearance and cost-effectiveness. RESULTS: Final outcomes were available for 496 patients, balanced for gender; mean age 44 years; initial facial paralysis moderate to severe. One half of patients initiated treatment within 24 hours of onset of symptoms, one-third within 24-48 hours and the remainder within 48-72 hours. Of the completed patients, 357 had recovered by 3 months and 80 at 9 months, leaving 59 with a residual deficit. There were significant differences in complete recovery at 3 months between the prednisolone comparison groups (83.0% for prednisolone, 63.6% for no prednisolone, a difference of + 19.4%; 95% confidence interval (CI): + 11.7% to + 27.1%, p < 0.001). The number needed to treat (NNT) in order to achieve one additional complete recovery was 6 (95% CI: 4 to 9). There was no significant difference between the aciclovir comparison groups (71.2% for aciclovir and 75.7% for no aciclovir). Nine-month assessments of patients recovered were 94.4% for prednisolone compared with 81.6% for no prednisolone, a difference of + 12.8% (95% CI: + 7.2% to + 18.4%, p < 0.001); the NNT was 8 (95% CI: 6 to 14). Proportions recovered at 9 months were 85.4% for aciclovir and 90.8% for no aciclovir, a difference of -5.3%. There was no significant prednisolone-aciclovir interaction at 3 months or at 9 months. Outcome differences by individual treatment (the four-arm model) showed significant differences. At 3 months the recovery rate was 86.3% in the prednisolone treatment group, 79.7% in the aciclovir-prednisolone group, 64.7% in the placebo group and 62.5% in the aciclovir group. At 9 months the recovery rates were respectively 96.1%, 92.7%, 85.3% and 78.1%. The increase in recovery rate conferred by the addition of prednisolone (both for prednisolone over placebo and for aciclovir-prednisolone over aciclovir) is highly statistically significant (p < 0.001). There were no significant differences in secondary measures apart from Health Utilities Index Mark 3 (HUI3) at 9 months in those treated with prednisolone. CONCLUSIONS: This study provided robust evidence to support the early use of oral prednisolone in Bell's palsy as an effective treatment which may be considered cost-effective. Treatment with aciclovir, either alone or with steroids, had no effect on outcome.

Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: a record-linkage population cohort study and decision analysis (ALFIE).

OBJECTIVES: To determine the natural history of abnormalities in liver function tests (LFTs), derive predictive algorithms for liver disease and identify the most cost-effective strategies for further investigation. DATA SOURCES: MEDLINE database from 1966 to September 2006, EMBASE, CINAHL and the Cochrane Library. METHODS: Population-based retrospective cohort study set in primary care in Tayside, Scotland, between 1989 and 2003. Participants were patients with no obvious signs of liver disease and registered with a general practitioner (GP). The study followed up those with an incident batch of LFTs in primary care to subsequent liver disease or mortality over a maximum of 15 years. The health technologies being assessed were primary care LFTs, viral and autoantibody tests, ultrasound and liver biopsy. Measures used were the epidemiology of liver disease in Tayside (ELDIT) database, time-to-event modelling, predictive algorithms derived using the Weibull survival model, decision analyses from an NHS perspective, cost-utility analyses, and one-way and two-way sensitivity analyses. RESULTS: A total of 95,977 patients had 364,194 initial LFTs, with a median follow-up of 3.7 years. Of these, 21.7% had at least one abnormal liver function test (ALFT) and 1090 (1.14%) developed liver disease. Elevated transaminases were strongly associated with diagnosed liver disease, with hazard ratios (HRs) of 4.23 [95% CI (confidence interval) 3.55-5.04] for mild levels and 12.67 (95% CI 9.74-16.47) for severe levels versus normal. For gamma-glutamyltransferase (GGT), these HRs were 2.54 (95% CI 2.17-2.96) and 13.44 (10.71-16.87) respectively. Low albumin was strongly associated with all cause mortality, with ratios of 2.65 (95% CI 2.47-2.85) for mild levels and 4.99 (95% CI 4.26-5.84) for severe levels. Sensitivity for predicting events over 5 years was low and specificity was high. Follow-up time was split into baseline to 3 months, 3 months to 1 year and over 1 year. All LFTs were predictive of liver disease, and high probability of liver disease was associated with being female, methadone use, alcohol dependency and deprivation. The shorter-term models had overall c-statistics of 0.85 and 0.72 for outcome of liver disease at 3 months and 1 year respectively, and 0.88 and 0.82 for all cause mortality at 3 months and 1 year respectively. Calibration was good for models predicting liver disease. Discrimination was low for models predicting events at over 1 year. In cost-utility analyses, retesting dominated referral as an option. However, using the predictive algorithms to identify the top percentile at high risk of liver disease, retesting had an incremental cost-utility ratio of 7588 pounds relative to referral. CONCLUSIONS: GGT should be included in the batch of LFTs in primary care. If the patient in primary care has no obvious liver disease and a low or moderate risk of liver disease, retesting in primary care is the most cost-effective option. If the patient with ALFTs in primary care has a high risk of liver disease, retesting depends on the willingness to pay of the NHS. Cut-offs are arbitrary and in developing decision aids it is important to treat the LFT results as continuous variables.

Patients' experiences of a diagnosis of Hughes' syndrome.

The objectives of the study were to describe the experience of patients immediately prior to a diagnosis of Hughes syndrome (HS) or antiphospholipid syndrome and post-diagnosis. A questionnaire survey was carried out set in the Hughes Syndrome Foundation, St. Thomas' Hospital, London, 2006. Participants were all patients who are members of the Hughes Syndrome Foundation. The main outcome measures were responses to a questionnaire relating to the experiences of people with a diagnosis of HS, such as number of hospitalisations, number of consultants seen, number of miscarriages, etc. A total of 157 patients completed the questionnaire, giving a response rate of 60.4%. Most (85%) were women and mean age was 46 years (SD 12). The median time to diagnosis was 3 years. The median number of consultants seen was 2 (max 19) with a median time in hospital pre-diagnosis of 10 days. The most common initial diagnoses were migraines, multiple sclerosis and systemic lupus erythematosus. Among women, 46% had had a miscarriage. Two thirds of respondents thought a blood test would have led to an earlier diagnosis. Comments from patients indicated a lack of awareness among specialists and general practitioners. The survey demonstrated a long time lag for diagnosis of Hughes syndrome, with increased costs to the NHS and emotional and financial cost to the patient. Greater awareness of this condition would benefit patients and the NHS.

Economic evaluation of early administration of prednisolone and/or aciclovir for the treatment of Bell's palsy.

OBJECTIVES: Bell's palsy (BP), which causes facial paralysis, affects 11-40 people per 100 000 per annum in the UK. Its cause is unknown but as many as 30% of patients have continuing facial disfigurement, psychological difficulties and occasionally facial pain. We present an randomised controlled trial (RCT)-based economic evaluation of the early administration of steroids (prednisolone) and/or antivirals (acyclovir) compared to placebo, for treatment of BP. METHODS: The RCT was not powered to detect differences in the cost-effectiveness; therefore, we adopted a decision analytic model approach as a way of gaining precision in our cost-effectiveness comparisons [e.g. prednisolone only (PO) versus acyclovir only versus prednisolone and acyclovir versus placebo, prednisolone versus no prednisolone (NP) and acyclovir versus no acyclovir]. We assumed that trial interventions affect the probability of being cured/not cured but their consequences are independent of the initial therapy. We used the percentage of individuals with a complete recovery (based on House-Brackmann grade = 1) at 9 months and Quality Adjusted Life Years (e.g. derived on responses to the Health Utilities Index III) as measures of effectiveness. Other parameter estimates were obtained from trial data. RESULTS: PO dominated-i.e. was less costly and more effective-all other therapy strategies in the four arms model [77% probability of cost-effective (CE)]. Moreover, Prednisolone dominated NP (77% probability of being CE at 30 000 UK pounds threshold) while no acyclovir dominated aciclovir (85% chance of CE), in the two arms models, respectively. CONCLUSIONS: Treatment of BP with prednisolone is likely to be considered CE while treatment with acyclovir is highly unlikely to be considered CE. Further data on costs and utilities would be useful to confirm findings.

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.

Long-term adherence to statin treatment in diabetes.

AIMS: To determine the patterns and predictors of long-term adherence to statin therapy in all patients with diabetes in the community setting. METHODS: We retrospectively studied patients with diabetes who were resident in Tayside, Scotland from 1 January 1989 to 31 May 2003 and initiated statin treatment during that time. The main outcome measure was percentage of days covered (PDC) by a statin, calculated at regular intervals. Predictors of suboptimal adherence (PDC < 80%) were identified using generalized linear models for repeated measures. RESULTS: Six thousand four hundred and sixty-two patients were included in the study. In the first year, the mean PDC was 87, 61% in the first and second quarter, respectively, and 65% after 13 years. Less than 50% of patients maintained a PDC of > 80% after 13 years. Predictors of poor long-term adherence were younger age, higher HbA(1c), no history of smoking, no cardiovascular morbidity at baseline and occurrence of cardiovascular disease after statin commencement. CONCLUSIONS: This study suggests that barriers to long-term adherence to statins tend to arise early on in the therapeutic course. In general, long-term adherence is poor in patients with diabetes, especially among those with few other cardiovascular risk factors.

Diagnosis of left ventricular systolic dysfunction (LVSD): development and validation of a clinical prediction rule in primary care.

BACKGROUND: Diagnosing suspected left ventricular systolic dysfunction (LVSD) in the community is a challenge for GPs. We developed and validated a clinical prediction rule (CPR) for LVSD based on history, examination and electrocardiogram (ECG). METHODS: Prospective cohort studies of 458 symptomatic patients (derivation cohort) and 535 patients (validation cohort) in 26 general practices in Tayside and Fife, Scotland. All patients underwent a structured clinical examination and ECG and the 'reference standard' investigation of echocardiography to establish the presence of LVSD. RESULTS: Four elements from the clinical history and examination were all independently associated with LVSD--male sex [adjusted odds ratio (OR) 2.5; 95% CI 1.1, 5.0], presence of orthopnoea (OR 5.4; 1.9, 13.8) history of myocardial infarction (OR 5.6; 2.3, 13.6) and elevated jugular venous pulsations (OR 15.1; 4.6, 49.3). Addition of ECG (OR 20.6; 2.7, 158.6) provides important diagnostic information in terms of probability of LVSD. A CPR based on the presence or absence of these five elements will generate probabilities ranging from 1% to 97% for LVSD when applied to an individual patient. In the validation cohort, the model under-predicted the probability of LVSD, particularly at lower levels of expected risk, reflecting differences in the risk-factor profiles of the derivation and validation cohorts. CONCLUSIONS: The derived CPR provides quantitative estimates of post-test probability for LVSD. This rule requires further validation in other populations and settings because of the difficulties encountered in the validation cohort.