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.

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.

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.

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.

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.

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.

A study of the safety of current gastrointestinal endoscopy (EGD).

BACKGROUND AND STUDY AIMS: Previous attempts at assessing the safety of upper gastrointestinal endoscopy have been hampered by incomplete data collection. We aimed to assess the 30-day mortality associated with esophagogastroduodenoscopy (EGD) and assess the important risk factors. PATIENTS AND METHODS: A retrospective cohort study was conducted of patients who underwent endoscopy at Ninewells Hospital in Dundee between 1 June 2000 and 31 May 2003. A total of 11 501 EGDs were performed in 8926 patients. These patients were record-linked to the death registry and the database of hospital admissions in order to calculate the all-cause 30-day mortality. An expert panel judged whether EGD had caused or contributed to the deaths. Logistic regression analysis was performed on outcomes of all-cause and EGD-contributed mortality. RESULTS: The median age of the patients was 62 years (interquartile range 48 - 74 years), 54 % were women, and 94 % of procedures were diagnostic. A total of 395 patients died within 30 days (all-cause 30-day mortality rate 4.4 %). One patient death was caused directly by the EGD (procedure-caused mortality rate 1 in 9000). EGD was judged to have contributed to patient deaths at a rate of 1 in 182, based on majority agreement of experts: some factors associated with these deaths were percutaneous endoscopic gastrostomy insertion (odds ratio [OR] 18.39, 95 % confidence interval [CI] 5.71 - 59.22), melena or hematemesis indications (OR 9.01, 95 % CI 3.53 - 22.99), and esophageal varices (OR 6.28, 95 % CI 1.54 - 25.60). CONCLUSIONS: A causal death rate of 1 in 9000 suggests that EGD is very safe. However, certain patient groups have an increased mortality, and the risks and benefits of EGD should be carefully evaluated in each patient.

Patient, carer and health service outcomes of nurse-led early discharge after breast cancer surgery: a randomised controlled trial.

Patients with breast cancer who require axillary clearance traditionally remain in hospital until their wound drains are removed. Early discharge has been shown to improve clinical outcomes, but there has been little assessment of the psychosocial and financial impact of early discharge on patients, carers and the health service. This study aimed to evaluate the effectiveness of a nurse-led model of early discharge from hospital. Main outcome measures were quality of life and carer burden. Secondary outcomes included patient satisfaction, arm morbidity, impact on community nurses, health service costs, surgical cancellations and in-patient nursing dependency. A total of 108 patients undergoing axillary clearance with mastectomy or wide local excision for breast cancer were randomised to nurse-led early discharge or conventional stay. Nurse-led early discharge had no adverse effects on quality of life or patient satisfaction, had little effect on carer burden, improved communication between primary and secondary care, reduced cancellations and was safely implemented in a mixed rural/urban setting. In total, 40% of eligible patients agreed to take part. Nonparticipants were significantly older, more likely to live alone and had lower emotional well being before surgery. This study provides further evidence of the benefits of early discharge from hospital following axillary clearance for breast cancer. However, if given the choice, most patients prefer to stay in hospital until their wound drains are removed.

Factors influencing time from presentation to treatment of colorectal and breast cancer in urban and rural areas.

Stage at diagnosis and survival from cancer vary according to where people live, suggesting some may have delays in diagnosis. The aim of this study was to determine if time from presentation to treatment was longer for colorectal and breast cancer patients living further from cancer centres, and identify other important factors in delay. Data were collected on 1097 patients with breast and 1223 with colorectal cancer in north and northeast Scotland. Women with breast cancer who lived further from cancer centres were treated more quickly than those living closer to cancer centres (P=0.011). Multilevel modelling found that this was largely due to them receiving earlier treatment at hospitals other than cancer centres. Breast lump, change in skin contour, lymphadenopathy, more symptoms and signs, and increasing age predicted faster treatment. Screen detected cancers and private referrals were treated more quickly. For colorectal cancer, time to treatment was similar for people in rural and urban areas. Quicker treatment was associated with palpable rectal or abdominal masses, tenesmus, abdominal pain, frequent GP consultations, age between 50 and 74 years, tumours of the transverse colon, and iron medication at presentation. Delay was associated with past anxiety or depression. There was variation between general practices and treatment appeared quicker at practices with more female general practitioners.

Prognosis following first acute myocardial infarction in Type 2 diabetes: a comparative population study.

AIMS: To estimate the incidence of death and macrovascular complications after a first myocardial infarction for patients with Type 2 diabetes. RESEARCH DESIGN: In a retrospective, incidence cohort study in the Tayside Region of Scotland we studied all patients hospitalized with a diagnosis of first acute myocardial infarction from 1 April 1993 to 31 December 1994. The primary endpoint was time to death. Secondary endpoints were 2-year incidence of hospital admission for angina, myocardial infarction, stroke, heart failure, coronary angiography, coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA). RESULTS: The 147 patients with Type 2 diabetes had significantly worse survival with an increase in relative hazard of 67% compared with non-diabetic patients. After adjustment for age, sex, smoking status, prior heart failure, prior angina, delay to hospitalization, site of infarction, drug therapy with aspirin, beta-blockers, streptokinase and hyperlipidaemia and treated hypertension, Type 2 diabetes was still associated with a 40% higher death rate compared with people without diabetes (P < 0.05) There was no significant difference in death rates in those aged over 70 years, but an indication of a trend in younger individuals with a four-fold increase in death rate in those with diabetes aged < 60 years, compared with a rate ratio of 2.6 in those with diabetes aged 61-70 years. CONCLUSIONS: Among hospitalized patients with first acute myocardial infarction, Type 2 diabetes mellitus is consistently associated with increased mortality and increased hospital admission for heart failure. The estimated 4-year survival rate is only 50%. Our results indicate that younger subjects with Type 2 diabetes and acute myocardial infarction are a high-risk group deserving of special study, and support the argument for aggressive targeting of coronary risk factors among patients with Type 2 diabetes.

Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study.

OBJECTIVE: To examine whether allopurinol is associated with any alteration in mortality and hospitalisations in patients with chronic heart failure (CHF). This hypothesis is based on previous data that a high urate concentration is independently associated with mortality with a risk ratio of 4.23 in CHF. DESIGN: Retrospective cohort study. SETTING: Medicines Monitoring Unit, Ninewells Hospital, Dundee, UK. PATIENTS: 1760 CHF patients divided into four groups: those on no allopurinol, those on long term low dose allopurinol, those on short term low dose allopurinol, and those on long term high dose allopurinol. MAIN OUTCOME MEASURES: Total mortality, cardiovascular mortality, cardiovascular hospitalisations, cardiovascular mortality or hospitalisations. RESULTS: Long term low dose allopurinol was associated with a significant worsening in mortality over those who never received allopurinol (relative risk 2.04, 95% confidence interval (CI) 1.48 to 2.81). This may be because low dose allopurinol is insufficient to negate the adverse effect of a high urate concentration. However, long term high dose (> or = 300 mg/day) allopurinol was associated with a significantly better mortality than longstanding low dose allopurinol (relative risk 0.59, 95% CI 0.37 to 0.95). This may mean that high dose allopurinol can fully negate the adverse effect of urate and return the mortality to normal. CONCLUSIONS: Long term high dose allopurinol may be associated with a better mortality than long term low dose allopurinol in patients with CHF because of a dose related beneficial effect of allopurinol against the well described adverse effect of urate. Further work is required to substantiate or refute this finding.

Cost effectiveness of computer tailored and non-tailored smoking cessation letters in general practice: randomised controlled trial.

OBJECTIVES: To develop and evaluate, in a primary care setting, a computerised system for generating tailored letters about smoking cessation. DESIGN: Randomised controlled trial. SETTING: Six general practices in Aberdeen, Scotland. PARTICIPANTS: 2553 smokers aged 17 to 65. INTERVENTIONS: All participants received a questionnaire asking about their smoking. Participants subsequently received either a computer tailored or a non-tailored, standard letter on smoking cessation, or no letter. MAIN OUTCOME MEASURES: Prevalence of validated abstinence at six months; change in intention to stop smoking in the next six months. RESULTS: The validated cessation rate at six months was 3.5% (30/857) (95% confidence interval 2.3% to 4.7%) for the tailored letter group, 4.4% (37/846) (3.0% to 5.8%) for the non-tailored letter group, and 2.6% (22/850) (1.5% to 3.7%) for the control (no letter) group. After adjustment for significant covariates, the cessation rate was 66% greater (-4% to 186%; P=0.07) in the non-tailored letter group than that in the no letter group. Among participants who smoked <20 cigarettes per day, the cessation rate in the non-tailored letter group was 87% greater (0% to 246%; P=0.05) than that in the no letter group. Among heavy smokers who did not quit, a 76% higher rate of positive shift in "stage of change" (intention to quit within a particular period of time) was seen compared with those who received no letter (11% to 180%; P=0.02). The increase in cost for each additional quitter in the non-tailored letter group compared with the no letter group was pound 89. CONCLUSIONS: In a large general practice, a brief non-tailored letter effectively increased cessation rates among smokers. A tailored letter was not effective in increasing cessation rates but promoted shift in movement towards cessation ("stage of change") in heavy smokers. As a pragmatic tool to encourage cessation of smoking, a mass mailing of non-tailored letters from general practices is more cost effective than computer tailored letters or no letters.

Physical activity level is an independent predictor of the diurnal variation in blood pressure.

OBJECTIVE: The aim of this study was to define the relationship between physical activity and the magnitude of the percentage fall in blood pressure at night (nocturnal dip). METHODS: We simultaneously monitored 24-h ambulatory blood pressure and measured physical activity by actigraphy in 434 patients. Blood pressure was measured every 20 min; the actigraph integrated an activity score every 10 s. Mean daytime and night-time activity were calculated from mean scores for the 15 min preceding each blood pressure measurement. Nocturnal dip in systolic and diastolic blood pressure (SBP and DBP) were regressed on mean (log-transformed) daytime activity. Mean night-time activity, age, gender, smoking status, body mass index (BMI) and clinic blood pressure were added into a multiple linear regression. RESULTS: The patient group was heterogeneous in age, gender and mean 24-h blood pressure. Mean daytime activity level was significantly and positively associated with the magnitude of the nocturnal dip in both SBP and DBP. Increased night-time activity was significantly associated with a smaller nocturnal dip. Older patients had a smaller nocturnal dip per log unit daytime activity. Nocturnal dip in SBP was greater in males, and smaller in those taking antihypertensive medications. Smoking, BMI and clinical blood pressure level were not associated with the extent of the nocturnal dip after adjustment for other factors. CONCLUSIONS: Daytime and night-time physical activity levels are independently and significantly predictive of the magnitude of the nocturnal dip in blood pressure. Variation in activity may confound interpretation of 24-h ambulatory blood pressure monitoring, and contribute to the poor reproducibility of dipper status.

Training pharmacists and pharmacy assistants in the stage-of-change model of smoking cessation: a randomised controlled trial in Scotland.

OBJECTIVE: To evaluate a training workshop for community pharmacy personnel to improve their counselling in smoking cessation based on the stage-of-change model. DESIGN: A randomised controlled trial of community pharmacies and pharmacy customers. SETTING: All 76 non-city community pharmacies registered in Grampian, Scotland, were invited to participate. Sixty-two pharmacies (82%) were recruited. SUBJECTS: All the intervention pharmacy personnel were invited to attend the training; 40 pharmacists and 54 assistants attended. A total of 492 customers who smoked (224 intervention, 268 controls) were recruited during the 12-month recruitment period (overall recruitment rate 63%). MAIN OUTCOME MEASURES: The perceptions of customers and pharmacy personnel of the pharmacy support and self-reported smoking cessation rates for the two groups of customers at one, four, and nine months. RESULTS: The intervention customer respondents were significantly more likely to have discussed stopping smoking with pharmacy personnel, 85% (113) compared with 62% (99) of the controls (p < 0.001). The former also rated their discussion more highly; 34% (45) of the intervention customers compared with 16% (25) of the controls rated it as "very useful" (p = 0.048). Assuming non-responders had lapsed, one-month point prevalence of abstinence was claimed by 30% of intervention customers and 24% of controls (p = 0.12); four months' continuous abstinence was claimed by 16% of intervention customers and 11% of controls (p = 0.094); and nine months' continuous abstinence was claimed by 12% of intervention customers and 7% of controls (p = 0.089). These trends in outcome were not affected by potential confounders (sex, age, socioeconomic status, nicotine dependence, and type of nicotine replacement product used) or adjustment for clustering. CONCLUSIONS: The intervention was associated with increased and more highly rated counselling, and a trend toward higher smoking cessation rates, indicating that community pharmacy personnel have the potential to make a significant contribution to national smoking cessation targets.

Alcohol intake as a risk factor for peripheral arterial disease in the general population in the Edinburgh Artery Study.

The aim of this study was to determine the relationship between alcohol consumption and occurrence of peripheral arterial disease in the general population. During 1988 in a cross sectional survey, the Edinburgh Artery Study, 1,592 men and women aged 55-74 years were selected at random from the age-sex registers of ten general practices distributed geographically and socio-economically across the city. participants were asked to recall the number of units of wine, beer and spirits consumed in the previous week and whether or not this was typical. Peripheral arterial disease was measured using the ankle brachial pressure index (ABPI). Men and women were analysed separately because of large differences in alcohol consumption. There was no association between ABPI and alcohol consumption in women but, in men, increasing alcohol consumption was associated with a higher ABPI (test for trend, p = 0.03) indicating less severe disease. This relationship was linear rather than U-shaped. In multiple regression analysis, after age-adjustment the ABPI was related to wine consumption but not beer or spirits in men (p < or = 0.01). On adjusting for age and cumulative lifetime cigarette smoking, the association of wine consumption with the ABPI was diminished but remained statistically significant (p < 0.05). On adjusting for age and social class, the relationship of total alcohol intake and wine consumption with the ABPI became non significant (p > 0.05). We conclude that in males, greater alcohol consumption is related to a higher ABPI and that any protective 'effect' of alcohol relates to wine consumption rather than beer or spirits.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex differences in susceptibility to etiologic factors for peripheral atherosclerosis. Importance of plasma fibrinogen and blood viscosity.

Cardiovascular risk factors in men, such as cigarette smoking, hypercholesterolemia, and hypertension, also increase risk in women, but the relative susceptibility to risk factors between the sexes is not established. Our aim was to investigate a wide range of possible etiologic factors in a single population study and identify those that were more strongly related to peripheral atherosclerosis in men or women. We studied personal factors (age and social class), lifestyle factors (smoking, exercise, alcohol intake, and dietary nutrients), and intermediary factors (obesity, diabetes, serum lipids, coagulation, and rheological factors). In the Edinburgh Artery Study in 1988 we measured cardiovascular risk factors in a random population sample of 1592 men and women aged 55 to 74 years. The ankle-brachial pressure index (ABPI), which is inversely related to the degree of peripheral atherosclerosis, was assessed in each subject. Lifetime cigarette smoking was correlated with a lower ABPI equally in men and women (r = -.27, P < .001). Dietary nutrients and alcohol intake were not related differently between the sexes with ABPI. However, recall of strenuous and moderate leisure time exercise during the age range of 35 to 45 years was related more strongly to a higher ABPI in men than in women (P < .05). Plasma fibrinogen, plasma viscosity, and blood viscosity were the only intermediary factors that had stronger univariate correlations with lower ABPI in men than in women. On multivariate analysis, the sex differences persisted for plasma fibrinogen (P < .05) and blood viscosity (P < .001); high-density lipoprotein cholesterol was related to ABPI in men only (sex difference, P < .1).(ABSTRACT TRUNCATED AT 250 WORDS)