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1.  Reproductive Outcomes Following Ectopic Pregnancy: Register-Based Retrospective Cohort Study 
PLoS Medicine  2012;9(6):e1001243.
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
doi:10.1371/journal.pmed.1001243
PMCID: PMC3378618  PMID: 22723747
2.  Authors’ response 
doi:10.3399/bjgp14X676311
PMCID: PMC3876152  PMID: 24567554
3.  A 5-year observational study of cancellations in the operating room: Does the introduction of preoperative preparation have an impact? 
Saudi Journal of Anaesthesia  2014;8(Suppl 1):S8-S14.
Background:
Preoperative preparation (assessment) of patients reduces cancellations on the day of surgery. A Center for Reviews and Dissemination review (2007) concluded “the evidence was weak and it was uncertain that preassessment reduced cancellations.” The aim of this study was to observe the impact of a preoperative preparation clinic on cancellations of operating room cases on the day of surgery, and in particular on those causes of cancellation on the day of surgery which were expected to be affected by preoperative preparation.
Materials and Methods:
Observational study conducted in a 194 bed District General Hospital in the United Kingdom from April 1, 2006 to March 31, 2011. 42,082 operating room cases were scheduled for operation during this period. Surgical sessions which did not require anesthetic input were excluded. Contemporaneous data were collected and analyzed on a monthly basis, and also grouped by year over a 5-year period. The cancellations on the day of surgery were divided into two groups: Those considered to be affected by preoperative preparation and those which were not. Comparisons were made between these two groups and between individual reasons for cancellation.
Results:
A total of 28,928 cases met the inclusion criteria. The clinic introduction reduced cancellations considered to be affected by preoperative preparation from 462 to 177 (78% and 42% total cancellations, respectively) (P < 0.001). There was a decrease in cancellations due to patients who did not arrive (P < 0.001) and medical reasons (P < 0.001), but an increase in the number of cancellations by the patients themselves (P = 0.002). Cancellations due to lack of beds and “other” reasons both increased (P < 0.001) across the study period.
Conclusions:
This study suggests that the introduction of preoperative preparation clinics for patients reduces cancellations on the day of surgery.
doi:10.4103/1658-354X.144053
PMCID: PMC4268536  PMID: 25538529
Anesthesia; assessment; cancelled procedures; preoperative care
4.  Increased Use of Twitter at a Medical Conference: A Report and a Review of the Educational Opportunities 
Background
Most consider Twitter as a tool purely for social networking. However, it has been used extensively as a tool for online discussion at nonmedical and medical conferences, and the academic benefits of this tool have been reported. Most anesthetists still have yet to adopt this new educational tool. There is only one previously published report of the use of Twitter by anesthetists at an anesthetic conference. This paper extends that work.
Objective
We report the uptake and growth in the use of Twitter, a microblogging tool, at an anesthetic conference and review the potential use of Twitter as an educational tool for anesthetists.
Methods
A unique Twitter hashtag (#WSM12) was created and promoted by the organizers of the Winter Scientific Meeting held by The Association of Anaesthetists of Great Britain and Ireland (AAGBI) in London in January 2012. Twitter activity was compared with Twitter activity previously reported for the AAGBI Annual Conference (September 2011 in Edinburgh). All tweets posted were categorized according to the person making the tweet and the purpose for which they were being used. The categories were determined from a literature review.
Results
A total of 227 tweets were posted under the #WSM12 hashtag representing a 530% increase over the previously reported anesthetic conference. Sixteen people joined the Twitter stream by using this hashtag (300% increase). Excellent agreement (κ = 0.924) was seen in the classification of tweets across the 11 categories. Delegates primarily tweeted to create and disseminate notes and learning points (55%), describe which session was attended, undertake discussions, encourage speakers, and for social reasons. In addition, the conference organizers, trade exhibitors, speakers, and anesthetists who did not attend the conference all contributed to the Twitter stream. The combined total number of followers of those who actively tweeted represented a potential audience of 3603 people.
Conclusions
This report demonstrates an increase in uptake and growth in the use of Twitter at an anesthetic conference and the review illustrates the opportunities and benefits for medical education in the future.
doi:10.2196/jmir.2144
PMCID: PMC3799570  PMID: 23232765
Twitter messaging; Social Media; Conferences; Congresses; Anesthesiology
5.  Mortality and morbidity after initial diagnostic excision biopsy of cutaneous melanoma in primary versus secondary care 
The British Journal of General Practice  2013;63(613):e563-e572.
Background
Current UK melanoma guidelines do not support the initial diagnostic excision biopsy of pigmented lesions in primary care, although this is standard in other countries such as Australia. Previous research in Northeast Scotland found that initial diagnostic excision biopsies in primary care that prove to be melanoma were no more likely to be incomplete than those performed in secondary care, but data on longer-term outcomes were not available.
Aim
To determine whether initial diagnostic excision biopsy of cutaneous melanoma in primary versus secondary care leads to poorer survival and increased morbidity.
Design and setting
Analysis of a linked dataset comprising pathological data from melanoma cases diagnosed in Northeast Scotland between 1991 and 2007, the General Registry Office (Scotland) death registry, and an NHS Scotland episode of care database.
Method
Patient data from three sources were matched using the Community Health Index (CHI) number. Cox proportional hazards regression, with robust standard error estimates, was used to examine the hazard ratio (95% confidence interval) of key mortality and morbidity outcomes based on excision in primary versus secondary care. Analysis was conducted before and after adjustment for operator and patient-level factors, using a multilevel approach.
Results
Patients receiving their initial diagnostic excision biopsy for melanoma in primary versus secondary care were no more likely to be dead, or to have died of metastatic malignant melanoma. Patients who had their initial diagnostic excision biopsy for melanoma in primary care had significantly fewer subsequent hospital admissions and spent fewer days in hospital.
Conclusion
These findings suggest that initial diagnostic excision biopsy of melanoma in primary care does not lead to poorer long-term outcomes.
doi:10.3399/bjgp13X670697
PMCID: PMC3722833  PMID: 23972197
early detection of cancer; melanoma; primary health care; skin neoplasms; surgical procedures, minor
6.  Elevated fasting plasma cortisol is associated with ischaemic heart disease and its risk factors in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study 
Context
Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk.
Objective
We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischaemic heart disease in people with type 2 diabetes.
Design
Cross-sectional cohort study including 919 men and women aged 67.9 (4.2) years with type 2 diabetes, the Edinburgh Type 2 Diabetes Study
Setting
General community
Intervention
Measurement of fasting morning plasma cortisol
Main outcome measurement
Associations between cortisol levels, features of the metabolic syndrome, obesity and ischaemic heart disease
Results
Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (p<0.001). These findings remained significant after adjustment for potential confounding factors (p<0.001). Elevated cortisol levels were associated with prevalent ischaemic heart disease (>800 vs. <600nmol/l, OR 1.58, p=0.02). This association remained significant after adjustment for duration and control of diabetes and other cardiovascular risk factors (p=0.03).
Conclusions
The previously described associations between HPA axis activation and features of the metabolic syndrome are present among people with type 2 diabetes. Elevated plasma cortisol is also associated with a greater prevalence of ischaemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischaemic heart disease merits further exploration.
doi:10.1210/jc.2009-2112
PMCID: PMC3971455  PMID: 20130072
cortisol; type 2 diabetes; metabolic syndrome; ischaemic heart disease
7.  Reducing the time before consulting with symptoms of lung cancer: a randomised controlled trial in primary care 
Background
Most individuals with lung cancer have symptoms for several months before presenting to their GP. Earlier consulting may improve survival.
Aim
To evaluate whether a theory-based primary care intervention increased timely consulting of individuals with symptoms of lung cancer.
Design and setting
Open randomised controlled trial comparing intervention with usual care in two general practices in north-east Scotland.
Method
Smokers and ex-smokers aged ≥55 years were randomised to receive a behavioural intervention or usual care. The intervention comprised a single nurse consultation at participants’ general practice and a self-help manual. The main outcomes were consultations within target times for individuals with new chest symptoms (≤3 days haemoptysis, ≤3 weeks other symptoms) in the year after the intervention commenced, and intentions about consulting with chest symptoms at 1 and 6 months.
Results
Two hundred and twelve participants were randomised and 206 completed the trial. The consultation rate for new chest symptoms in the intervention group was 1.19 (95% confidence interval [CI] = 0.92 to 1.53; P = 0.18) times higher than in the usual-care group and the proportion of consultations within the target time was 1.11 (95% CI = 0.41 to 3.03; P = 0.83) times higher. One month after the intervention commenced, the intervention group reported intending to consult with chest symptoms 31 days (95% CI = 7 to 54; P = 0.012) earlier than the usual care group, and at 6 months this was 25 days (95% CI = 1.5 to 48; P = 0.037) earlier.
Conclusion
Behavioural intervention in primary care shortened the time individuals at high risk of lung disease intended to take before consulting with new chest symptoms (the secondary outcome of the study), but increases in consultation rates and the proportions of consultations within target times were not statistically significant.
doi:10.3399/bjgp13X660779
PMCID: PMC3529292  PMID: 23336469
early detection of cancer; general practice; illness behaviour; lung neoplasms; randomised controlled trial
8.  Assessing Risk Prediction Models Using Individual Participant Data From Multiple Studies 
Pennells, Lisa | Kaptoge, Stephen | White, Ian R. | Thompson, Simon G. | Wood, Angela M. | Tipping, Robert W. | Folsom, Aaron R. | Couper, David J. | Ballantyne, Christie M. | Coresh, Josef | Goya Wannamethee, S. | Morris, Richard W. | Kiechl, Stefan | Willeit, Johann | Willeit, Peter | Schett, Georg | Ebrahim, Shah | Lawlor, Debbie A. | Yarnell, John W. | Gallacher, John | Cushman, Mary | Psaty, Bruce M. | Tracy, Russ | Tybjærg-Hansen, Anne | Price, Jackie F. | Lee, Amanda J. | McLachlan, Stela | Khaw, Kay-Tee | Wareham, Nicholas J. | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Jansson, Jan-Håkan | Wennberg, Patrik | Salomaa, Veikko | Harald, Kennet | Jousilahti, Pekka | Vartiainen, Erkki | Woodward, Mark | D'Agostino, Ralph B. | Bladbjerg, Else-Marie | Jørgensen, Torben | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Dekker, Jacqueline M. | Nijpels, Giel | Stehouwer, Coen D. A. | Kauhanen, Jussi | Salonen, Jukka T. | Meade, Tom W. | Cooper, Jackie A. | Cushman, Mary | Folsom, Aaron R. | Psaty, Bruce M. | Shea, Steven | Döring, Angela | Kuller, Lewis H. | Grandits, Greg | Gillum, Richard F. | Mussolino, Michael | Rimm, Eric B. | Hankinson, Sue E. | Manson, JoAnn E. | Pai, Jennifer K. | Kirkland, Susan | Shaffer, Jonathan A. | Shimbo, Daichi | Bakker, Stephan J. L. | Gansevoort, Ron T. | Hillege, Hans L. | Amouyel, Philippe | Arveiler, Dominique | Evans, Alun | Ferrières, Jean | Sattar, Naveed | Westendorp, Rudi G. | Buckley, Brendan M. | Cantin, Bernard | Lamarche, Benoît | Barrett-Connor, Elizabeth | Wingard, Deborah L. | Bettencourt, Richele | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Kavousi, Maryam | Witteman, Jacqueline C. | Hofman, Albert | Franco, Oscar H. | Howard, Barbara V. | Zhang, Ying | Best, Lyle | Umans, Jason G. | Onat, Altan | Sundström, Johan | Michael Gaziano, J. | Stampfer, Meir | Ridker, Paul M. | Michael Gaziano, J. | Ridker, Paul M. | Marmot, Michael | Clarke, Robert | Collins, Rory | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimäki, Mika | Ridker, Paul M. | Buring, Julie | Cook, Nancy | Ford, Ian | Shepherd, James | Cobbe, Stuart M. | Robertson, Michele | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S. | Angelantonio, Emanuele Di | Gao, Pei | Haycock, Philip | Kaptoge, Stephen | Pennells, Lisa | Thompson, Simon G. | Walker, Matthew | Watson, Sarah | White, Ian R. | Wood, Angela M. | Wormser, David | Danesh, John
American Journal of Epidemiology  2013;179(5):621-632.
Individual participant time-to-event data from multiple prospective epidemiologic studies enable detailed investigation into the predictive ability of risk models. Here we address the challenges in appropriately combining such information across studies. Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for coronary heart disease in the Emerging Risk Factors Collaboration, a collation of individual data from multiple prospective studies with an average follow-up duration of 9.8 years (dates varied). We derive risk prediction models using Cox proportional hazards regression analysis stratified by study and obtain estimates of risk discrimination, Harrell's concordance index, and Royston's discrimination measure within each study; we then combine the estimates across studies using a weighted meta-analysis. Various weighting approaches are compared and lead us to recommend using the number of events in each study. We also discuss the calculation of measures of reclassification for multiple studies. We further show that comparison of differences in predictive ability across subgroups should be based only on within-study information and that combining measures of risk discrimination from case-control studies and prospective studies is problematic. The concordance index and discrimination measure gave qualitatively similar results throughout. While the concordance index was very heterogeneous between studies, principally because of differing age ranges, the increments in the concordance index from adding log C-reactive protein to conventional risk factors were more homogeneous.
doi:10.1093/aje/kwt298
PMCID: PMC3927974  PMID: 24366051
C index; coronary heart disease; D measure; individual participant data; inverse variance; meta-analysis; risk prediction; weighting
9.  Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 323 275 person years 
Objectives To determine whether maternal obesity during pregnancy is associated with increased mortality from cardiovascular events in adult offspring.
Design Record linkage cohort analysis.
Setting Birth records from the Aberdeen Maternity and Neonatal databank linked to the General Register of Deaths, Scotland, and the Scottish Morbidity Record systems.
Population 37 709 people with birth records from 1950 to present day.
Main outcome measures Death and hospital admissions for cardiovascular events up to 1 January 2012 in offspring aged 34-61. Maternal body mass index (BMI) was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on outcomes in offspring was tested with time to event analysis with Cox proportional hazard regression to compare outcomes in offspring of mothers in underweight, overweight, or obese categories of BMI compared with offspring of women with normal BMI.
Results All cause mortality was increased in offspring of obese mothers (BMI >30) compared with mothers with normal BMI after adjustment for maternal age at delivery, socioeconomic status, sex of offspring, current age, birth weight, gestation at delivery, and gestation at measurement of BMI (hazard ratio 1.35, 95% confidence interval 1.17 to 1.55). In adjusted models, offspring of obese mothers also had an increased risk of hospital admission for a cardiovascular event (1.29, 1.06 to 1.57) compared with offspring of mothers with normal BMI. The offspring of overweight mothers also had a higher risk of adverse outcomes.
Conclusions Maternal obesity is associated with an increased risk of premature death in adult offspring. As one in five women in the United Kingdom is obese at antenatal booking, strategies to optimise weight before pregnancy are urgently required.
doi:10.1136/bmj.f4539
PMCID: PMC3805484  PMID: 23943697
10.  Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis 
Wormser, David | Angelantonio, Emanuele Di | Kaptoge, Stephen | Wood, Angela M | Gao, Pei | Sun, Qi | Walldius, Göran | Selmer, Randi | Verschuren, WM Monique | Bueno-de-Mesquita, H Bas | Engström, Gunnar | Ridker, Paul M | Njølstad, Inger | Iso, Hiroyasu | Holme, Ingar | Giampaoli, Simona | Tunstall-Pedoe, Hugh | Gaziano, J Michael | Brunner, Eric | Kee, Frank | Tosetto, Alberto | Meisinger, Christa | Brenner, Hermann | Ducimetiere, Pierre | Whincup, Peter H | Tipping, Robert W | Ford, Ian | Cremer, Peter | Hofman, Albert | Wilhelmsen, Lars | Clarke, Robert | de Boer, Ian H | Jukema, J Wouter | Ibañez, Alejandro Marín | Lawlor, Debbie A | D'Agostino, Ralph B | Rodriguez, Beatriz | Casiglia, Edoardo | Stehouwer, Coen DA | Simons, Leon A | Nietert, Paul J | Barrett-Connor, Elizabeth | Panagiotakos, Demosthenes B | Björkelund, Cecilia | Strandberg, Timo E | Wassertheil-Smoller, Sylvia | Blazer, Dan G | Meade, Tom W | Welin, Lennart | Svärdsudd, Kurt | Woodward, Mark | Nissinen, Aulikki | Kromhout, Daan | Jørgensen, Torben | Tilvis, Reijo S | Guralnik, Jack M | Rosengren, Annika | Taylor, James O | Kiechl, Stefan | Dagenais, Gilles R | Gerry, F | Fowkes, R | Wallace, Robert B | Khaw, Kay-Tee | Shaffer, Jonathan A | Visser, Marjolein | Kauhanen, Jussi | Salonen, Jukka T | Gallacher, John | Ben-Shlomo, Yoav | Kitamura, Akihiko | Sundström, Johan | Wennberg, Patrik | Kiyohara, Yutaka | Daimon, Makoto | de la Cámara, Agustin Gómez | Cooper, Jackie A | Onat, Altan | Devereux, Richard | Mukamal, Kenneth J | Dankner, Rachel | Knuiman, Matthew W | Crespo, Carlos J | Gansevoort, Ron T | Goldbourt, Uri | Nordestgaard, Børge G | Shaw, Jonathan E | Mussolino, Michael | Nakagawa, Hidaeki | Fletcher, Astrid | Kuller, Lewis H | Gillum, Richard F | Gudnason, Vilmundur | Assmann, Gerd | Wald, Nicholas | Jousilahti, Pekka R | Greenland, Philip | Trevisan, Maurizio | Ulmer, Hanno | Butterworth, Adam S | Folsom, Aaron R | Davey-Smith, George | Hu, Frank B | Danesh, John | Tipping, Robert W | Ford, Charles E | Simpson, Lara M | Walldius, Göran | Jungner, Ingmar | Folsom, Aaron R | Demerath, Ellen W | Franceschini, Nora | Lutsey, Pamela L | Panagiotakos, Demosthenes B | Pitsavos, Christos | Chrysohoou, Christina | Stefanadis, Christodoulos | Shaw, Jonathan E | Atkins, Robert | Zimmet, Paul Z | Barr, Elizabeth LM | Knuiman, Matthew W | Whincup, Peter H | Wannamethee, S Goya | Morris, Richard W | Willeit, Johann | Kiechl, Stefan | Weger, Siegfried | Oberhollenzer, Friedrich | Wald, Nicholas | Ebrahim, Shah | Lawlor, Debbie A | Gallacher, John | Ben-Shlomo, Yoav | Yarnell, John WG | Casiglia, Edoardo | Tikhonoff, Valérie | Greenland, Philip | Shay, Christina M | Garside, Daniel B | Nietert, Paul J | Sutherland, Susan E | Bachman, David L | Keil, Julian E | de Boer, Ian H | Kizer, Jorge R | Psaty, Bruce M | Mukamal, Kenneth J | Nordestgaard, Børge G | Tybjærg-Hansen, Anne | Jensen, Gorm B | Schnohr, Peter | Giampaoli, Simona | Palmieri, Luigi | Panico, Salvatore | Pilotto, Lorenza | Vanuzzo, Diego | de la Cámara, Agustin Gómez | Simons, Leon A | Simons, Judith | McCallum, John | Friedlander, Yechiel | Gerry, F | Fowkes, R | Price, Jackie F | Lee, Amanda J | Taylor, James O | Guralnik, Jack M | Phillips, Caroline L | Wallace, Robert B | Kohout, Frank J | Cornoni-Huntley, Joan C | Guralnik, Jack M | Blazer, Dan G | Guralnik, Jack M | Phillips, Caroline L | Phillips, Caroline L | Guralnik, Jack M | Khaw, Kay-Tee | Wareham, Nicholas J | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Rothenbacher, Dietrich | Wennberg, Patrik | Jansson, Jan-Håkan | Nissinen, Aulikki | Donfrancesco, Chiara | Giampaoli, Simona | Woodward, Mark | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | D'Agostino, Ralph B | Vasan, Ramachandran S | Fox, Caroline S | Pencina, Michael J | Daimon, Makoto | Oizumi, Toshihide | Kayama, Takamasa | Kato, Takeo | Bladbjerg, Else-Marie | Jørgensen, Torben | Møller, Lars | Jespersen, Jørgen | Dankner, Rachel | Chetrit, Angela | Lubin, Flora | Svärdsudd, Kurt | Eriksson, Henry | Welin, Lennart | Lappas, Georgios | Rosengren, Annika | Lappas, Georgios | Welin, Lennart | Svärdsudd, Kurt | Eriksson, Henry | Lappas, Georgios | Bengtsson, Calle | Lissner, Lauren | Björkelund, Cecilia | Cremer, Peter | Nagel, Dorothea | Strandberg, Timo E | Salomaa, Veikko | Tilvis, Reijo S | Miettinen, Tatu A | Tilvis, Reijo S | Strandberg, Timo E | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Rodriguez, Beatriz | Dekker, Jacqueline M | Nijpels, Giel | Stehouwer, Coen DA | Hu, Frank B | Sun, Qi | Rimm, Eric B | Willett, Walter C | Iso, Hiroyasu | Kitamura, Akihiko | Yamagishi, Kazumasa | Noda, Hiroyuki | Goldbourt, Uri | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | Kauhanen, Jussi | Salonen, Jukka T | Kurl, Sudhir | Tuomainen, Tomi-Pekka | Poppelaars, Jan L | Deeg, Dorly JH | Visser, Marjolein | Meade, Tom W | De Stavola, Bianca Lucia | Hedblad, Bo | Nilsson, Peter | Engström, Gunnar | Verschuren, WM Monique | Blokstra, Anneke | de Boer, Ian H | Shea, Steven J | Meisinger, Christa | Thorand, Barbara | Koenig, Wolfgang | Döring, Angela | Verschuren, WM Monique | Blokstra, Anneke | Bueno-de-Mesquita, H Bas | Wilhelmsen, Lars | Rosengren, Annika | Lappas, Georgios | Fletcher, Astrid | Nitsch, Dorothea | Kuller, Lewis H | Grandits, Greg | Tverdal, Aage | Selmer, Randi | Nystad, Wenche | Mussolino, Michael | Gillum, Richard F | Hu, Frank B | Sun, Qi | Manson, JoAnn E | Rimm, Eric B | Hankinson, Susan E | Meade, Tom W | De Stavola, Bianca Lucia | Cooper, Jackie A | Bauer, Kenneth A | Davidson, Karina W | Kirkland, Susan | Shaffer, Jonathan A | Shimbo, Daichi | Kitamura, Akihiko | Iso, Hiroyasu | Sato, Shinichi | Holme, Ingar | Selmer, Randi | Tverdal, Aage | Nystad, Wenche | Nakagawa, Hidaeki | Miura, Katsuyuki | Sakurai, Masaru | Ducimetiere, Pierre | Jouven, Xavier | Bakker, Stephan JL | Gansevoort, Ron T | van der Harst, Pim | Hillege, Hans L | Crespo, Carlos J | Garcia-Palmieri, Mario R | Kee, Frank | Amouyel, Philippe | Arveiler, Dominique | Ferrières, Jean | Schulte, Helmut | Assmann, Gerd | Jukema, J Wouter | de Craen, Anton JM | Sattar, Naveed | Stott, David J | Cantin, Bernard | Lamarche, Benoît | Després, Jean-Pierre | Dagenais, Gilles R | Barrett-Connor, Elizabeth | Bergstrom, Jaclyn | Bettencourt, Richele R | Buisson, Catherine | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Trevisan, Maurizio | Hofman, Albert | Ikram, M Arfan | Tiemeier, Henning | Witteman, Jacqueline CM | Tunstall-Pedoe, Hugh | Tavendale, Roger | Lowe, Gordon DO | Woodward, Mark | Devereux, Richard | Yeh, Jeun-Liang | Ali, Tauqeer | Calhoun, Darren | Ben-Shlomo, Yoav | Davey-Smith, George | Onat, Altan | Can, Günay | Nakagawa, Hidaeki | Sakurai, Masaru | Nakamura, Koshi | Morikawa, Yuko | Njølstad, Inger | Mathiesen, Ellisiv B | Løchen, Maja-Lisa | Wilsgaard, Tom | Sundström, Johan | Ingelsson, Erik | Michaëlsson, Karl | Cederholm, Tommy | Gaziano, J Michael | Buring, Julie | Ridker, Paul M | Gaziano, J Michael | Ridker, Paul M | Ulmer, Hanno | Diem, Günter | Concin, Hans | Rodeghiero, Francesco | Tosetto, Alberto | Wassertheil-Smoller, Sylvia | Manson, JoAnn E | Marmot, Michael | Clarke, Robert | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimaki, Mika | Ridker, Paul M | Buring, Julie | Ford, Ian | Robertson, Michele | Ibañez, Alejandro Marín | Feskens, Edith | Geleijnse, Johanna M | Kromhout, Daan | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S | Angelantonio, Emanuele Di | Franco, Oscar H | Gao, Pei | Gobin, Reeta | Haycock, Philip | Kaptoge, Stephen | Seshasai, Sreenivasa R Kondapally | Lewington, Sarah | Pennells, Lisa | Rapsomaniki, Eleni | Sarwar, Nadeem | Thompson, Alexander | Thompson, Simon G | Walker, Matthew | Watson, Sarah | White, Ian R | Wood, Angela M | Wormser, David | Zhao, Xiaohui | Danesh, John
Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual–participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.
Results For people born between 1900 and 1960, mean adult height increased 0.5–1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96–0.99) for death from any cause, 0.94 (0.93–0.96) for death from vascular causes, 1.04 (1.03–1.06) for death from cancer and 0.92 (0.90–0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12–1.42) for risk of melanoma death to 0.84 (0.80–0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
Conclusion Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
doi:10.1093/ije/dys086
PMCID: PMC3465767  PMID: 22825588
Height; cardiovascular disease; cancer; cause-specific mortality; epidemiological study; meta-analysis
11.  Developing a complex intervention to reduce time to presentation with symptoms of lung cancer 
The British Journal of General Practice  2012;62(602):e605-e615.
Background
Lung cancer is the commonest cause of cancer in Scotland and is usually advanced at diagnosis. Median time between symptom onset and consultation is 14 weeks, so an intervention to prompt earlier presentation could support earlier diagnosis and enable curative treatment in more cases.
Aim
To develop and optimise an intervention to reduce the time between onset and first consultation with symptoms that might indicate lung cancer.
Design and setting
Iterative development of complex healthcare intervention according to the MRC Framework conducted in Northeast Scotland.
Method
The study produced a complex intervention to promote early presentation of lung cancer symptoms. An expert multidisciplinary group developed the first draft of the intervention based on theory and existing evidence. This was refined following focus groups with health professionals and high-risk patients.
Results
First draft intervention components included: information communicated persuasively, demonstrations of early consultation and its benefits, behaviour change techniques, and involvement of spouses/partners. Focus groups identified patient engagement, achieving behavioural change, and conflict at the patient–general practice interface as challenges and measures were incorporated to tackle these. Final intervention delivery included a detailed self-help manual and extended consultation with a trained research nurse at which specific action plans were devised.
Conclusion
The study has developed an intervention that appeals to patients and health professionals and has theoretical potential for benefit. Now it requires evaluation.
doi:10.3399/bjgp12X654579
PMCID: PMC3426599  PMID: 22947581
early diagnosis; health services research; lung cancer; primary health care
12.  ‘Help for Hay Fever’, a goal-focused intervention for people with intermittent allergic rhinitis, delivered in Scottish community pharmacies: study protocol for a pilot cluster randomized controlled trial 
Trials  2013;14:217.
Background
Despite the availability of evidence-based guidelines for managing allergic rhinitis in primary care, management of the condition in the United Kingdom (UK) remains sub-optimal. Its high prevalence and negative effects on quality of life, school performance, productivity and co-morbid respiratory conditions (in particular, asthma), and high health and societal costs, make this a priority for developing novel models of care. Recent Australian research demonstrated the potential of a community pharmacy-based ‘goal-focused’ intervention to help people with intermittent allergic rhinitis to self-manage their condition better, reduce symptom severity and improve quality of life. In this pilot study we will assess the transferability of the goal-focused intervention to a UK context, the suitability of the intervention materials, procedures and outcome measures and collect data to inform a future definitive UK randomized controlled trial (RCT).
Methods/Design
A pilot cluster RCT with associated preliminary economic analysis and embedded qualitative evaluation. The pilot trial will take place in two Scottish Health Board areas: Grampian and Greater Glasgow & Clyde. Twelve community pharmacies will be randomly assigned to intervention or usual care group. Each will recruit 12 customers seeking advice or treatment for intermittent allergic rhinitis. Pharmacy staff in intervention pharmacies will support recruited customers in developing strategies for setting and achieving goals that aim to avoid/minimize triggers for, and eliminate/minimize symptoms of allergic rhinitis. Customers recruited in non-intervention pharmacies will receive usual care. The co-primary outcome measures, selected to inform a sample size calculation for a future RCT, are: community pharmacy and customer recruitment and completion rates; and effect size of change in the validated mini-Rhinoconjunctivitis Quality of Life Questionnaire between baseline, one-week and six-weeks post-intervention. Secondary outcome measures relate to changes in symptom severity, productivity, medication adherence and self-efficacy. Quantitative data about accrual, retention and economic measures, and qualitative data about participants’ experiences during the trial will be collected to inform the future RCT.
Discussion
This work will lay the foundations for a definitive RCT of a community pharmacy-based ‘goal-focused’ self-management intervention for people with intermittent allergic rhinitis. Results of the pilot trial are expected to be available in April 2013.
Trial registration
Current Controlled Trials ISRCTN43606442
doi:10.1186/1745-6215-14-217
PMCID: PMC3721993  PMID: 23856015
Respiratory; Allergy; Community pharmacy; Self-care
13.  Anticipatory care planning and integration: a primary care pilot study aimed at reducing unplanned hospitalisation 
The British Journal of General Practice  2012;62(595):e113-e120.
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.
doi:10.3399/bjgp12X625175
PMCID: PMC3268490  PMID: 22520788
admission; advance care planning; end-of-life care; general practice; patient readmission
14.  Genital HSV-2 Infection Induces Short-Term NK Cell Memory 
PLoS ONE  2012;7(3):e32821.
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.
doi:10.1371/journal.pone.0032821
PMCID: PMC3310819  PMID: 22457721
15.  Primary excision of cutaneous melanoma: does the location of excision matter 
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.
doi:10.3399/bjgp11X556272
PMCID: PMC3026152  PMID: 21276340
cancer; melanoma; primary health care; skin neoplasms; surgical procedures, minor
16.  Diabetic Retinopathy and Cognitive Decline in Older People With Type 2 Diabetes 
Diabetes  2010;59(11):2883-2889.
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.
doi:10.2337/db10-0752
PMCID: PMC2963547  PMID: 20798334
17.  A questionnaire to measure melanoma risk, knowledge and protective behaviour: Assessing content validity in a convenience sample of Scots and Australians 
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.
doi:10.1186/1471-2288-11-123
PMCID: PMC3236020  PMID: 21867531
18.  Impact of lifestyle in middle-aged women on mortality: evidence from the Royal College of General Practitioners' Oral Contraception Study 
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.
doi:10.3399/bjgp10X515052
PMCID: PMC2913736  PMID: 20822689
epidemiology; follow-up studies; lifestyle; mortality; women
19.  Effectiveness of inhaler types for real-world asthma management: retrospective observational study using the GPRD 
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.
doi:10.2147/JAA.S17709
PMCID: PMC3116791  PMID: 21698214
asthma control; dry powder inhaler; breath-actuated inhaler; metered-dose inhaler; primary care
20.  Morning Cortisol Levels and Cognitive Abilities in People With Type 2 Diabetes 
Diabetes Care  2010;33(4):714-720.
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.
doi:10.2337/dc09-1796
PMCID: PMC2845011  PMID: 20097784
21.  Association Between Raised Inflammatory Markers and Cognitive Decline in Elderly People With Type 2 Diabetes 
Diabetes  2009;59(3):710-713.
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.
doi:10.2337/db09-1163
PMCID: PMC2828661  PMID: 19959761
22.  Authors’ reply 
BMJ : British Medical Journal  2008;336(7635):60.
doi:10.1136/bmj.39450.650289.3A
PMCID: PMC2190231
23.  Cost-effectiveness analysis of corticosteroid inhaler devices in primary care asthma management: A real world observational study 
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.
PMCID: PMC3169968  PMID: 21935316
asthma control; breath-actuated inhaler; dry powder inhaler; metered dose inhaler; incremental cost-effectiveness ratio
24.  Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study 
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.
doi:10.1136/bmj.c927
PMCID: PMC2837145  PMID: 20223876
25.  An intercalated BSc degree is associated with higher marks in subsequent medical school examinations 
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.
doi:10.1186/1472-6920-9-24
PMCID: PMC2689211  PMID: 19454007

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