Background

Anticipatory care for older patients who are frail involves both case identification and proactive intervention to reduce hospitalisation.

Aim

To identify a population who were at risk of admission to hospital and to provide an anticipatory care plan (ACP) for them and to ascertain whether using primary and secondary care data to identify this population and then applying an ACP can help to reduce hospital admission rates.

Design and setting

Cohort study of a service intervention in a general practice and a primary care team in Scotland.

Method

The ACP sets out patients’ wishes in the event of a sudden deterioration in health. If admitted, a proactive approach was taken to transfer and discharge patients into the community. Cohorts were selected using the Nairn Case Finder, which matched patients in two practices for age, sex, multiple morbidity indexes, and secondary care outpatient and inpatient activity; 96 patients in each practice were studied for admission rate, occupied bed days and survival.

Results

Survivors from the ACP cohort (n = 80) had 510 fewer days in hospital than in the 12 months pre-intervention: a significant reduction of 52.0% (P = 0.020). There were 37 fewer admissions of the survivors from that cohort post-intervention than in the preceding 12 months, with a significant reduction of 42.5% (P = 0.002). Mortality rates in the two cohorts were similar, but the number of patients who died in hospital and the hospital bed days used in the last 3 months of life were significantly lower for the decedents with an ACP than for the controls who had died (P = 0.007 and P = 0.045 respectively).

Conclusion

This approach produced statistically significant reductions in unplanned hospitalisation for a cohort of patients with multiple morbidities. It demonstrates the potential for providing better care for patients as well as better value for health and social care services. It is of particular benefit in managing end-of-life care.

Using Scottish national registry data, Sohinee Bhattacharya and colleagues investigate pregnancy outcomes following ectopic pregnancy in comparison to livebirth, miscarriage, or termination in a first pregnancy.

Background

We aimed to compare reproductive outcomes following ectopic pregnancy (EP) versus livebirth, miscarriage, or termination in a first pregnancy.

Methods And Findings

A retrospective cohort study design was used. Scottish national data on all women whose first pregnancy occurred between 1981 and 2000 were linked to records of a subsequent pregnancy. The exposed cohort comprised women with an EP in their first pregnancy. There were three unexposed cohorts: women with livebirth, miscarriage, and termination of their first pregnancies. Any differences in rates of second pregnancy, livebirth, EP, miscarriage, or terminations and complications of a second ongoing pregnancy and delivery were assessed among the different exposure groups. A total of 2,969 women had an initial EP; 667,299 had a livebirth, 39,705 women miscarried, and 78,697 terminated their first pregnancies. Women with an initial EP had an increased chance of another pregnancy within 2 years (adjusted hazard ratio (AHR) 2.76 [95% CI 2.58–2.95]) or after 6 years (AHR 1.57 [95% CI 1.29–1.91]) compared to women with a livebirth. In comparison with women with an initial miscarriage, women who had an EP had a lower chance of a second pregnancy (AHR 0.53 [95% CI 0.50–0.56]). Compared to women with an initial termination, women with an EP had an increased chance of a second pregnancy (AHR 2.38 [95% CI 2.23–2.55]) within 2 years. Women with an initial EP suffered an increased risk of another EP compared to women with a livebirth (AHR 13.0 [95% CI 11.63–16.86]), miscarriage (AHR 6.07 [95% CI 4.83–7.62]), or termination (AHR 12.84 [95% CI 10.07–16.37]). Perinatal complications in a pregnancy following EP were not significantly higher than those in primigravidae or in women with a previous miscarriage or termination.

Conclusion

Women with an initial EP have a lower chance of conception than those who miscarry but an increased risk of a repeat EP in comparison with all three comparison groups. A major limitation of this study was the inability to separate women using contraception from those who were intending to conceive.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

An ectopic pregnancy occurs when the embryo (fertilized egg) implants outside the uterine cavity, usually in the fallopian tubes but sometimes in the cervix, ovaries, or abdomen. The prevalence for this condition is between 1%–2% of all pregnancies, and risk factors are thought to include pelvic infection, smoking, previous pelvic surgery, and use of certain types of intrauterine contraceptive devices. Ectopic pregnancies are potentially life threatening because as the fetus grows, it can lead to tubal rupture and abdominal bleeding—for example, in the UK, ectopic pregnancies are responsible for almost three-quarters of early pregnancy-related deaths. However, due to improvements in early diagnosis, in high income countries, deaths from ectopic pregnancies have become increasingly rare.

Why Was This Study Done?

Having an ectopic pregnancy can have serious implications for future fertility and subsequent pregnancies but to date, there is little information on reproductive outcomes in women who have had an ectopic pregnancy. So in this study, the researchers used a population-based cohort of women in Scotland to examine future reproductive outcomes in women who had an initial ectopic pregnancy and then compare these outcomes to those in women following a successful (live birth) or unsuccessful (miscarriage or termination) intrauterine pregnancy.

What Did The Researchers Do And Find?

The researchers used a national database (The Scottish Morbidity Record) and hospital discharge information to identify women who had ectopic pregnancies, miscarriages, terminations, or on-going pregnancies between 1981–2000. Then, using unique linking identifiers, they were able to examine the outcomes of subsequent pregnancies and conducted a statistical analysis to investigate whether the first pregnancy outcome had any effect on second pregnancy outcomes.

 The researchers found that during the time period studied, in their first pregnancy, 2,969 women had an ectopic pregnancy, 39,705 women miscarried, 78,697 women underwent termination, and the majority, 667,299, gave birth to a live infant. The researchers then found that compared to women with an initial live birth, women with an ectopic pregnancy were 2.76 times more likely to conceive a second pregnancy within two years. However, compared to women whose first pregnancies ended in miscarriage, women with an initial ectopic pregnancy were significantly less likely to conceive a second time but had an increased chance of a second pregnancy within two years compared to women who terminated their first pregnancy. Importantly, the researchers found that women with an initial ectopic pregnancy had a higher risk of a further ectopic pregnancy compared to all the other groups of women. Furthermore, these women had a significantly higher risk of preeclampsia, preterm delivery, and emergency cesarean delivery in their next continuing pregnancy compared to women who had a previous live birth. However, these risks were not significantly higher than women who had an early loss in a first pregnancy.

What Do These Findings Mean?

These findings suggest that women with an initial ectopic pregnancy have a lower chance of conception than those who miscarry and also have an increased risk of a repeat ectopic pregnancy compared to women who experience miscarriage, termination, or a live birth in their first pregnancy. However, as the researchers did not have any information on contraception use, a major limitation of this study is the inability to separate women using contraception from those who were intending to conceive—women who experienced an ectopic pregnancy may not want to conceive again after a traumatic experience rather than being unable to conceive because of tubal damage. However, the results of this study may help doctors to counsel women with an ectopic pregnancy at the time of initial diagnosis and treatment, and in those willing to conceive again, offer follow-up to discuss future fertility and possible risks of subsequent pregnancy. Further research will help to investigate whether the site of ectopic pregnancy affects future reproductive outcomes.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001243.

The American Pregnancy Association and the UK National Health Service (NHS) Choices give information on ectopic pregnancy

The UK nonprofit organization Ectopic Pregnancy Trust provides support for individuals affected by ectopic pregnancy

NK cells are known as innate immune cells that lack immunological memory. Recently, it has been shown that NK cells remember encounters with chemical haptens that induce contact hypersensitivity and cytomegalovirus infection. Here, we show the existence of NK cell memory following HSV-2 infection. Stimulation with HSV-2 Ags led to higher IFNγ production in NK cells that were exposed 30 days previously to HSV-2, compared to NK cells from naïve mice. More importantly, this increased production of IFNγ in NK cells was independent of B- and T- lymphocytes and specific for the HSV-2 Ags. We also showed that previously exposed NK cells in a B- and T-lymphocyte free environment mediate protection against HSV-2 infection and they are necessary for the protection of mice against HSV-2 infection. Collectively, NK cells remember prior HSV-2 encounters independent of B- and T- lymphocytes leading to protection against HSV-2 mediated morbidity and mortality upon re-exposure.

Melanoma is diagnosed more quickly if primarily excised in primary care, but current guidelines discourage this. The reports of all melanomas excised in north-east Scotland between 1991 and 2007 were analysed for adequacy of excision. Reports were analysed blinded as to source. Of primary biopsies performed in primary care, 72.5% were reported as completely excised, compared with 69.7% of those performed in secondary care (P<0.612). The difference remained non-significant following adjustment for important confounders.

OBJECTIVE

Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.

RESEARCH DESIGN AND METHODS

In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60–75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.

RESULTS

After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.

CONCLUSIONS

DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.

Background

The aim of this study was to assess the content validity of a questionnaire to measure melanoma risk, knowledge and protective behaviour in a convenience sample of Scots and Australians. Australia has the highest melanoma incidence worldwide but has developed a culture of skin cancer avoidance with a long history of skin cancer primary prevention campaigns of proven effectiveness. Scotland has lower incidence, but has shown a greater rate of increase between 1985 and 2007. There is an urgent need in Scotland, therefore, to identify those groups at greatest risk and provide them with effective preventative advice.

Method

A self-administered postal survey was completed by four groups formed from convenience samples in two geographical locations (Northeast Scotland and Western Australia). In univariate analysis scores on personal risk, level of concern, protective behaviour, and knowledge were compared by nationality, previous skin cancer diagnosis and personally knowing someone with melanoma. Multivariate linear regression analysis modelled the influence of potential predictor variables upon each of the scores.

Results

540 people completed the questionnaire, 273 Scots (50.6%). 133 (24.6%) Scots and 83 (15.4%) Australians previously had melanoma or non-melanoma skin cancer, whilst 120 (22.2%) Scots and 190 (35.2%) Australians personally knew someone with melanoma. Australians had higher knowledge (p < 0.001), level of concern (p < 0.001) and protective behaviour (p < 0.001) scores than the Scottish. Australian nationality was the strongest independent predictor of a higher knowledge score (p < 0.001), followed by a previous skin cancer diagnosis (p = 0.003), personal knowledge of someone with melanoma (p = 0.011), female gender (p = 0.005) and higher education status (p < 0.001) (R2 = 0.163).

Conclusion

The questionnaire detected higher levels of knowledge and skin cancer protective behaviours in Australians than in Scottish people. This was expected and supports the content validity of the questionnaire and its value as a future research tool in the Scottish population.

Background

Although many individuals have multiple lifestyle risk factors, few studies have investigated the impact of lifestyle risk factor combinations among women.

Aim

To investigate the relationship between individual and combinations of lifestyle risk factors in middle-aged women with subsequent mortality, and to estimate the associated population attributable risks.

Design of study

Prospective cohort study.

Setting

Royal College of General Practitioners' (RCGP) Oral Contraception Study, UK.

Method

In 1994–1995, women remaining under follow-up in the RCGP Oral Contraception Study were sent a lifestyle survey, from which modifiable risk factors were identified: pack-years smoked, physical inactivity, never drinking versus consuming at least 7 units of alcohol weekly, and being underweight, overweight, or obese. The cohort was followed to December 2006 or death. Population attributable risks were calculated.

Results

Of 10 059 women studied, 896 died. Pack-years smoked (11–20 years: adjusted hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.46 to 2.27; >20 years: adjusted HR = 2.34, 95% CI = 2.00 to 2.74); never drinking alcohol (adjusted HR = 1.66, 95% CI = 1.34 to 2.05); being underweight (adjusted = HR 1.66, 95% CI = 1.03 to 2.68); and physical inactivity (<15 hours/week: adjusted HR = 1.73, 95% CI = 1.46 to 2.04) were significantly associated with mortality compared with their respective reference group. Women with multiple lifestyle risk factors had higher mortality risks than those reporting one factor. The population attributable risk of the combination of smoking, physical inactivity, body mass index outside normal range, and alcohol (never drinking or excess intake) was 59% (95% CI = 31% to 78%).

Conclusion

Assuming a causal relationship between lifestyle and mortality, avoidance of four lifestyle risk factors would have prevented 60% of the deaths. The importance of avoiding smoking and undertaking physical inactivity during midlife should continue to be emphasised.

Purpose:

Results of randomized controlled trials may not predict effectiveness of inhaled corticosteroids (ICS) in real-world clinical practice, where inhaler technique and device characteristics can influence effectiveness. We compared asthma outcomes for ICS delivered via three different inhaler devices: pressurized metered-dose inhaler (pMDI), breath-actuated MDI (BAI), and dry powder inhaler (DPI).

Patients and methods:

This retrospective database study evaluated 1-year outcomes for primary care patients with asthma aged 5–60 years prescribed their first ICS (initiation population) by pMDI (n = 39,746), BAI (n = 9809), or DPI (n = 6792), or their first ICS dose increase (step-up population) by pMDI (n = 6245), BAI (n = 1388), or DPI (n = 1536). Co-primary outcome measures were composite proxy measures of asthma control (no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory infection) and severe exacerbations (unscheduled hospital admission, emergency room attendance, or oral corticosteroids). Outcomes were adjusted for potential confounding factors identified during a baseline year.

Results:

In the initiation population, adjusted odds ratios (95% confidence intervals [CI]) for asthma control, as compared with pMDIs, were significantly better for BAIs (1.08 [1.02–1.14]) and DPIs (1.13 [1.06–1.21]), while adjusted exacerbation rate ratios (95% CI) were 1.00 (0.93–1.08) and 0.88 (0.81–0.95), respectively. In the step-up population, adjusted odds of asthma control were 1.21 (1.05–1.39) for BAIs and 1.13 (0.99–1.29) for DPIs; adjusted exacerbation rate ratios were 0.83 (0.71–0.98) for BAIs and 0.85 (0.74–0.98) for DPIs, compared with pMDIs.

Conclusion:

Inhaler device selection may have a bearing on clinical outcomes. Differences in real-world effectiveness among these devices require closer evaluation in well-designed prospective trials.

OBJECTIVE

People with type 2 diabetes are at increased risk of cognitive impairment but the mechanism is uncertain. Elevated glucocorticoid levels in rodents and humans are associated with cognitive impairment. We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.

RESEARCH DESIGN AND METHODS

This was a cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes, living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study). Cognitive abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility were tested, and a general cognitive ability factor, g, was derived. Prior intelligence was estimated from vocabulary testing, and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning plasma cortisol levels and cognitive ability and estimated cognitive change were tested. Models were adjusted for potential confounding and/or mediating variables including metabolic and cardiovascular variables.

RESULTS

In age-adjusted analyses, higher fasting cortisol levels were not associated with current g or with performance in individual cognitive domains. However, higher fasting cortisol levels were associated with greater estimated cognitive decline in g and in tests of working memory and processing speed, independent of mood, education, metabolic variables, and cardiovascular disease (P < 0.05).

CONCLUSIONS

High morning cortisol levels in elderly people with type 2 diabetes are associated with estimated age-related cognitive change. Strategies targeted at lowering cortisol action may be useful in ameliorating cognitive decline in individuals with type 2 diabetes.

OBJECTIVE

To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary–based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.

RESULTS

Higher IL-6 and TNF-α levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients −0.074 to −0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.

CONCLUSIONS

In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline.

Purpose:

To evaluate and compare real world cost-effectiveness of inhaled corticosteroids (ICS) administered by metered dose inhaler (MDI), breath-actuated MDI (BAI), or dry powder inhaler (DPI) in asthma.

Patients and methods:

This retrospective database study analyzed the direct health care costs and proportion of patients (aged 5–60 years) achieving asthma control over 1 year in two population groups: those starting ICS (initiation population) and those receiving a first increase in ICS dose (step-up population). Asthma control was defined as no unplanned asthma visits, oral corticosteroids, or antibiotics for lower respiratory infection; outcomes were adjusted for confounding variables. Cost-effectiveness of BAI and DPI were compared with MDI.

Results:

For the initiation population (n = 56,347), average annual health care costs per person (adjusted results), as compared with MDIs, were £9 higher (95% CI: −1.65 to 19.71) for BAIs and £32 higher (95% CI: 19.51 to 43.66) for DPIs. The probability of BAIs being the dominant strategy (more effective and less costly than MDIs) was 5% and of BAIs being more effective and more costly than MDIs was 94%. DPIs were consistently more effective and more costly than MDIs, with an incremental cost-effectiveness ratio of £1711 (95% CI: 760 to 3,576) per additional controlled patient per year. For the step-up population (n = 9169), mean total health care costs per person, (adjusted) as compared with MDIs, were £1 higher (95% CI: −27.28 to 31.55) for BAIs and £73 higher (95% CI: 44.48 to 103.29) for DPIs. The probability of BAIs being dominant was 48% and of BAIs being more effective but more costly than MDIs was 52%; the probability of DPIs being more effective but more costly than MDIs was 96%.

Conclusion:

The real world effectiveness of ICS inhalers may vary, and inhaler device selection for patients with asthma should take into consideration not only initial device cost but also the subsequent health care resource costs.

Objective To see if the mortality risk among women who have used oral contraceptives differs from that of never users.

Design Prospective cohort study started in 1968 with mortality data supplied by participating general practitioners, National Health Service central registries, or both.

Setting 1400 general practices throughout the United Kingdom.

Participants 46 112 women observed for up to 39 years, resulting in 378 006 woman years of observation among never users of oral contraception and 819 175 among ever users.

Main outcome measures Directly standardised adjusted relative risks between never and ever users for all cause and cause specific mortality.

Results 1747 deaths occurred in never users of oral contraception and 2864 in ever users. Compared with never users, ever users of oral contraception had a significantly lower rate of death from any cause (adjusted relative risk 0.88, 95% confidence interval 0.82 to 0.93). They also had significantly lower rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynaecological cancers combined; all circulatory disease; ischaemic heart disease; and all other diseases. They had higher rates of violent deaths. No association between overall mortality and duration of oral contraceptive use was observed, although some disease specific relations were apparent. An increased relative risk of death from any cause between ever users and never users was observed in women aged under 45 years who had stopped using oral contraceptives 5-9 years previously but not in those with more distant use. The estimated absolute reduction in all cause mortality among ever users of oral contraception was 52 per 100 000 woman years.

Conclusion Oral contraception was not associated with an increased long term risk of death in this large UK cohort; indeed, a net benefit was apparent. The balance of risks and benefits, however, may vary globally, depending on patterns of oral contraception usage and background risk of disease.

Background

To compare medical students on a modern MBChB programme who did an optional intercalated degree with their peers who did not intercalate; in particular, to monitor performance in subsequent undergraduate degree exams.

Methods

This was a retrospective, observational study of anonymised databases of medical student assessment outcomes. Data were accessed for graduates, University of Aberdeen Medical School, Scotland, UK, from the years 2003 to 2007 (n = 861). The main outcome measure was marks for summative degree assessments taken after intercalating.

Results

Of 861 medical students, 154 (17.9%) students did an intercalated degree. After adjustment for cohort, maturity, gender and baseline (3rd year) performance in matching exam type, having done an IC degree was significantly associated with attaining high (18–20) common assessment scale (CAS) marks in three of the six degree assessments occurring after the IC students rejoined the course: the 4th year written exam (p < 0.001), 4th year OSCE (p = 0.001) and the 5th year Elective project (p = 0.010).

Conclusion

Intercalating was associated with improved performance in Years 4 and 5 of the MBChB. This improved performance will further contribute to higher academic ranking for Foundation Year posts. Long-term follow-up is required to identify if doing an optional intercalated degree as part of a modern medical degree is associated with following a career in academic medicine.

Background

Screening of high-risk groups for peripheral arterial disease has been advocated because the condition underdiagnosed and secondary prevention can reduce cardiovascular event rates.

Aim

To establish the feasibility of screening for peripheral arterial disease in people aged 60 years or over with hypertension, and to estimate the potential to improve secondary preventive treatment.

Design of study

Pilot study and cross-sectional survey.

Setting

Large general practice in north-east Scotland.

Method

People aged 60 years or over with hypertension but no cardiovascular disease or diabetes were identified from computer records and invited to a screening clinic. Data were collected on ankle brachial pressure index (ABPI), preventive treatment, and risk factors.

Results

Of 705 potentially eligible patients, 443 (63%) agreed to participate. Sixty-four were excluded and 364 of 379 patients (96%) attended screening. Thirty patients had peripheral arterial disease (ABPI of 0.9 or less), of whom 24 (7%; 95% confidence interval [CI] = 4 to 10%) were previously undiagnosed. Fifteen (50%) patients took antiplatelets, 13 (45%) had cholesterol <5mmol/l, and 16 (53%) had blood pressure below 140/85 mmHg. Twenty-two (73%) patients were non-smokers, 14 (47%) had low-fat diets, two (7%) were physically active, and three (10%) ate recommended amounts of fruit and vegetables.

Conclusions

It is feasible to screen for peripheral arterial disease in primary care, but its prevalence is lower than anticipated. There is room for improvement in secondary preventive treatment and lifestyle, so a structured programme could still have important benefits for survival.

Objective To examine the absolute risks or benefits on cancer associated with oral contraception, using incident data.

Design Inception cohort study.

Setting Royal College of General Practitioners' oral contraception study.

Participants Directly standardised data from the Royal College of General Practitioners' oral contraception study.

Main outcome measures Adjusted relative risks between never and ever users of oral contraceptives for different types of cancer, main gynaecological cancers combined, and any cancer. Standardisation variables were age, smoking, parity, social class, and (for the general practitioner observation dataset) hormone replacement therapy. Subgroup analyses examined whether the relative risks changed with user characteristics, duration of oral contraception usage, and time since last use of oral contraception.

Results The main dataset contained about 339 000 woman years of observation for never users and 744 000 woman years for ever users. Compared with never users ever users had statistically significant lower rates of cancers of the large bowel or rectum, uterine body, and ovaries, tumours of unknown site, and other malignancies; main gynaecological cancers combined; and any cancer. The relative risk for any cancer in the smaller general practitioner observation dataset was not significantly reduced. Statistically significant trends of increasing risk of cervical and central nervous system or pituitary cancer, and decreasing risk of uterine body and ovarian malignancies, were seen with increasing duration of oral contraceptive use. Reduced relative risk estimates were observed for ovarian and uterine body cancer many years after stopping oral contraception, although some were not statistically significant. The estimated absolute rate reduction of any cancer among ever users was 45 or 10 per 100 000 woman years, depending on whether the main or general practitioner observation dataset was used.

Conclusion In this UK cohort, oral contraception was not associated with an overall increased risk of cancer; indeed it may even produce a net public health gain. The balance of cancer risks and benefits, however, may vary internationally, depending on patterns of oral contraception usage and the incidence of different cancers.

Background

Well-designed trials are required to assess if complementary and alternative medicine (CAM) is effective.

Aim

This study assessed the effectiveness of spiritual healing for asthma.

Design of study

Randomised, placebo-controlled trial.

Setting

Aberdeen, Scotland.

Method

This was a single-blind, three-armed randomised, controlled trial of spiritual healing for asthma, comparing the effectiveness of five sessions of spiritual healing with placebo (delivered by an actor), and with a control group receiving normal care only. The primary outcome measure was the Juniper Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes were forced expiratory flow in one second (FEV1), peak expiratory flow (PEF), HADS (Hospital Anxiety Depression Scale), SF-36 and MYMOP (Measure Yourself Medical Outcome Profile). Baseline and follow-up data were collected.

Results

Eighty-eight adult patients receiving pharmacological treatment for asthma participated. AQLQ scores improved significantly from baseline and the end of treatment in all groups (spiritual healing P = 0.008; ‘sham’ healing P = 0.001 and control P = 0.01) but there was no significant difference between groups (P = 0.57). These improvements were maintained at follow-up 1 for two of the groups (spiritual healing P = 0.016; sham healing P = 0.001 and control P = 0.09) but none of the groups showed an improvement at follow-up 2 (spiritual healing P = 0.161; sham healing P = 0.016 and control P = 0.11). Similar proportions of patients in each group showed a clinically important improvement in AQLQ score. Analysis of AQLQ scores at end of treatment and both follow-up periods indicated no significance between group differences. No consistent changes were seen in secondary outcome measures, possibly due to the small sample size.

Conclusion

Spiritual healing does not appear to have any specific affect on patient asthma related quality of life.

Background

Our professional development plan aimed to improve the primary care management of acute asthma, which is known to be suboptimal.

Methods

We invited 59 general practices in Grampian, Scotland to participate. Consenting practices were randomised to early and delayed intervention groups. Practices undertook audits of their management of all acute attacks (excluding children under 5 years) occurring in the 3 months preceding baseline, 6-months and 12-months study time-points. The educational programme [including feedback of audit results, attendance at a multidisciplinary interactive workshop, and formulation of development plan by practice teams] was delivered to the early group at baseline and to the delayed group at 6 months. Primary outcome measure was recording of peak flow compared to best/predicted at 6 months. Analyses are presented both with, and without adjustment for clustering.

Results

23 consenting practices were randomised: 11 to early intervention. Baseline practice demography was similar. Six early intervention practices withdraw before completing the baseline audit. There was no significant improvement in our primary outcome measure (the proportion with peak flow compared to best/predicted) at either the 6 or 12 month time points after adjustment for baseline and practice effects. However, the between group difference in the adjusted combined assessment score, whilst non-significant at 6 months (Early: 2.48 (SE 0.43) vs. Delayed 2.26 (SE 0.33) p = 0.69) reached significance at 12 m (Early:3.60 (SE 0.35) vs. Delayed 2.30 (SE 0.28) p = 0.02).

Conclusion

We demonstrated no significant benefit at the a priori 6-month assessment point, though improvement in the objective assessment of attacks was shown after 12 months. Our practice development programme, incorporating audit, feedback and a workshop, successfully engaged the healthcare team of participating practices, though future randomised trials of educational interventions need to recognise that effecting change in primary care practices takes time. Monitoring of the assessment of acute attacks proved to be a feasible and responsive indicator of quality care.

Background

Despite effective treatments, asthma outcomes remain suboptimal. Interest exists in complementary therapies, particularly in herbal remedies for asthma treatment, currently with inconclusive evidence of efficacy. The encapsulated botanical mixture AKL1 has anecdotal evidence of effectiveness in asthma.

Methods

We performed a randomised controlled cross over study comparing the effectiveness of AKL1 with indistinguishable placebo as add-on therapy in patients uncontrolled on standard asthma treatment. Thirty two adult asthmatics completed a 36 week trial consisting of a 4 week single blind run in period, during which placebo was added to usual treatment, a 12 week double blind active phase in which subjects received AKL1 or placebo, a single blind 8 week washout period receiving placebo and a final 12 week double blind cross-over active treatment phase. Daily diaries were kept of peak expiratory flow and symptoms, and spirometry, validated symptom and health status questionnaire scores and adverse events were monitored at study visits. Paired T tests were used to compare the effects of placebo and AKL1 on outcomes. Changes in outcome measures over treatment phases are presented as means and 95% confidence intervals (CI) of means.

Results

No significant differences in lung function (active-placebo) were found (Forced Expiratory Volume in 1 second: mean difference [95% CI] = 0.01 [-0.12 to 0.14] L, p = 0.9. Peak Expiratory Flow: -4.08 [-35.03 to 26.89]. L/min, p = 0.8).

Trends to clinical improvements favouring active treatment were however consistently seen in the patient-centered outcomes: Asthma Control Questionnaire mean difference (active – placebo) [95% CI] = -0.35 [-0.78 to 0.07], p = 0.10, Asthma Quality of Life Questionnaire mean difference 0.42 [-0.08 to 0.93], p = 0.09, Leicester Cough Questionnaire mean difference 0.49, [-0.18 to 1.16], p = 0.15.

Nine exacerbations occurred during placebo treatment and five whilst on AKL1. No significant adverse events were noted.

Conclusion

AKL1 treatment was well tolerated. No significant improvements in lung function, symptoms, or quality of life were seen, although consistent trends were seen to improvements in patient-centered outcomes. Further studies are needed.

Background

Patient-reported side effect questionnaires offer a simple method for the systematic measurement of drug-related side effects. In order to measure patients' inhaled corticosteroids (ICS) related side effect perceptions the 14-day retrospective Inhaled Corticosteroid Questionnaire (ICQ) was developed. In this research we aim to assess the construct validity and reliability of the ICQ and test its responsiveness to dose changes in adult asthma patients.

Methods

In a cross-sectional study, current inhaler users with asthma completed the ICQ (27 with non ICS inhaler; 61 BDP equivalent daily ICS low dose ≤400 μg; 62 mid dose 401–800 μg; and 105 with high dose >800 μg). We generated 3 construct validity hypotheses: 1) a hierarchical dose-response pattern for scoring of the individual items on the ICQ, and statistically significant differences in the scores of each of the 15 ICQ domains by ICS dose group 2) an association between ICS dose and ICQ scoring after adjusting for appropriate confounders in multiple regression; 3) greater convergence between local side effect domains than between systemic and local domains of the scale. Test-retest reliability was assessed on a randomly selected subgroup of patients (n = 73) who also completed the ICQ a second time after 7 days. In a separate longitudinal study, 61 patients with asthma completed the ICQ at baseline and after changing their daily ICS dose, at 2- and 6- months, in order to test the ICQ's responsiveness.

Results

All three construct validity hypotheses were well supported: 1) a statistically significant difference existed in scores for 14 domains, the high ICS dose group scoring highest; 2) ICS dose independently predicted ICQ scoring after adjusting for confounders; 3) greater convergence existed between local ICQ domains than between local and systemic domains. The ICQ had good reproducibility: test-retest intraclass correlation coefficients were ≥0.69 for all but the 'Facial Oedema' domain. In the longitudinal study, ICQ scores for 'Voice Problems' changed significantly at 2- and 6-months from baseline and other ICQ domains displayed trends in scoring change accordant with dose modulation at 6-months.

Conclusion

The ICQ has good dose-related discriminative properties, is valid, reliable, and shows potential responsiveness to ICS dose change.

Background: Previous studies investigating the health-related quality of life of those with peripheral arterial disease have focused on patients recruited from hospital clinics. The health-related quality of life of people with peripheral arterial disease in the general population is unknown.

Aims: We aimed to determine the health-related quality of life of people with intermittent claudication and asymptomatic peripheral arterial disease in the general population and to compare it with those with angina and those with no peripheral arterial disease or angina.

Design of study: Analysis of cross-sectional data from the 12-year follow-up of a population-based cohort.

Setting: Edinburgh, Scotland.

Method: Data from the Edinburgh Artery Study cohort's 12-year follow-up was analysed. Participants' peripheral arterial disease status was measured using the World Health Organisation intermittent claudication questionnaire and the ankle brachial pressure index. Self-assessed health-related quality of life data was collected using the SF-36 generic questionnaire. Health-related quality of life scores were calculated and their associations with peripheral arterial disease status groups were tested.

Results: Subjects with intermittent claudication had significantly worse median health-related quality of life scores than patients without claudication in all domains except social functioning and mental health. Patients with claudication had a significantly lower physical component summary score than those without claudication (P≤0.001). This association remained after adjustment for age, sex, social class, body mass index, smoking, and angina. Those with angina and claudication had significantly worse physical component summary scores than those with no peripheral arterial disease or angina (P≤0.001). No significant difference was found in health-related quality of life scores between those with asymptomatic peripheral arterial disease and those with no peripheral arterial disease even after multiple adjustment for confounding factors.

Conclusion: People with intermittent claudication in the community had impaired health-related quality of life related to reduced physical health, but asymptomatic peripheral arterial disease did not significantly affect health-related quality of life.

Objectives To investigate the long term risk (mean > 20 years) of death from all causes, cardiovascular disease, and cancer in women who had or had not had a hysterectomy.

Design Nested cohort study.

Setting Royal College of General Practitioners' oral contraception study.

Participants 7410 women (3705 flagged at the NHS central registries for cancer and death who had a hysterectomy during the oral contraception study and 3705 who were flagged but did not have the operation).

Main outcome measures Mortality from all causes, cardiovascular disease, and cancer.

Results 623 (8.4%) women had died by the end of follow-up (308 in the hysterectomy group and 315 in the non-hysterectomy group). Older women who had had a hysterectomy had a 6% reduced risk of death compared with women of a similar age who did not have the operation (adjusted hazard ratio 0.94, 95% confidence interval 0.75 to 1.18). Compared with young women who did not have a hysterectomy those who were younger at hysterectomy had an adjusted hazard ratio for all cause mortality of 0.82 (0.65 to 1.03). Hysterectomy was not associated with a significantly altered risk of mortality from cardiovascular disease or cancer regardless of age.

Conclusion Hysterectomy did not increase the risk of death in the medium to long term.

Objective To determine whether mobile phone based monitoring improves asthma control compared with standard paper based monitoring strategies.

Design Multicentre randomised controlled trial with cost effectiveness analysis.

Setting UK primary care.

Participants 288 adolescents and adults with poorly controlled asthma (asthma control questionnaire (ACQ) score ≥1.5) from 32 practices.

Intervention Participants were centrally randomised to twice daily recording and mobile phone based transmission of symptoms, drug use, and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring.

Main outcome measures Changes in scores on asthma control questionnaire and self efficacy (knowledge, attitude, and self efficacy asthma questionnaire (KASE-AQ)) at six months after randomisation. Assessment of outcomes was blinded. Analysis was on an intention to treat basis.

Results There was no significant difference in the change in asthma control or self efficacy between the two groups (ACQ: mean change 0.75 in mobile group v 0.73 in paper group, mean difference in change −0.02 (95% confidence interval −0.23 to 0.19); KASE-AQ score: mean change −4.4 v −2.4, mean difference 2.0 (−0.3 to 4.2)). The numbers of patients who had acute exacerbations, steroid courses, and unscheduled consultations were similar in both groups, with similar healthcare costs. Overall, the mobile phone service was more expensive because of the expenses of telemonitoring.

Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines standards. The mobile technology was not cost effective.

Trial registration Clinical Trials NCT00512837.

Objective To determine whether there is a relation between aortic diameter and morbidity and mortality in men screened for abdominal aortic aneurysm.

Design Prospective cohort study.

Setting Highland and Western Isles (a large, sparsely populated area of Scotland).

Participants 8146 men aged 65-74.

Main outcome measures Morbidity and mortality in relation to presence of abdominal aortic aneurysm and three categories of aortic diameter (≤24 mm, 25-29 mm, and ≥30 mm).

Results When screened, 414 men (5.1%) had an aneurysm (diameter ≥30 mm), 669 (8.2%) an aortic diameter of 25-29 mm, and 7063 (86.7%) an aortic diameter of ≤24 mm. The cohort was followed up for a median of 7.4 (interquartile range 6.9-8.2) years. Mortality was significantly associated with aortic diameter: 512 (7.2%) men in the ≤24 mm group died compared with 69 (10.3%) in the 25-29 mm group and 73 (17.6%) in the ≥30 mm group. The mortality risk in men with an aneurysm or with an aorta measuring 25-29 mm was significantly higher than in men with an aorta of ≤24 mm. The increased mortality risk in the 25-29 mm group was reduced when taking confounders such as smoking and known heart disease into account. After adjustment, compared with men with an aortic diameter of ≤24 mm, the risk of hospital admission for cardiovascular disease and chronic obstructive pulmonary disease was significantly higher in men with aneurysm and those with aortas measuring 25-29 mm. Men with an aneurysm also had an increased risk of hospital admission for cerebrovascular disease, atherosclerosis, peripheral arterial disease, and respiratory disease. In men with aortas measuring 25-29 mm, the risk of hospital admission with abdominal aortic aneurysm was significantly higher than in men with an aorta of ≤24 mm (adjusted hazard ratio 6.7, 99% confidence interval 3.4 to 13.2) and this increased risk became apparent two years after screening.

Conclusions Men with abdominal aortic aneurysm and those with aortic diameters measuring 25-29 mm have an increased risk of mortality and subsequent hospital admissions compared with men with an aorta diameter of ≤24 mm. Consideration should be given to control of risk factors and to rescreening men with aortas measuring 25-29 mm at index scanning.