Influenza-attributable burden in United Kingdom primary care.

Influenza is rarely laboratory-confirmed and the outpatient influenza burden is rarely studied due to a lack of suitable data. We used the Clinical Practice Research Datalink (CPRD) and surveillance data from Public Health England in a linear regression model to assess the number of persons consulting UK general practitioners (GP episodes) for respiratory illness, otitis media and antibiotic prescriptions attributable to influenza during 14 seasons, 1995-2009. In CPRD we ascertained influenza vaccination status in each season and risk status (conditions associated with severe influenza outcomes). Seasonal mean estimates of influenza-attributable GP episodes in the UK were 857 996 for respiratory disease including 68 777 for otitis media, with wide inter-seasonal variability. In an average season, 2·4%/0·5% of children aged <5 years and 1·3%/0·1% of seniors aged ⩾75 years had a GP episode for respiratory illness attributed to influenza A/B. Two-thirds of influenza-attributable GP episodes were estimated to result in prescription of antibiotics. These estimates are substantially greater than those derived from clinically reported influenza-like illness in surveillance programmes. Because health service costs of influenza are largely borne in general practice, these are important findings for cost-benefit assessment of influenza vaccination programmes.

Risk of colorectal cancer in general practice patients presenting with rectal bleeding, change in bowel habit or anaemia.

The aim was to use data routinely collected in general practice to assess the absolute risk of colorectal cancer in patients newly presenting to their general practitioner (GP) with relevant symptoms. Three cohorts were identified from patients attending a sample of UK general practices. Patients with new symptoms of rectal bleeding, changes in bowel habit or anaemia were identified, and their incident rate for colorectal cancer and the positive predictive value (PPV) of each symptom in the following 12 months were calculated by age and gender. The total population over the age of 40 years was 2.8 million, and 9143 incident cases of colorectal cancer were identified. A total of 67,164 patients (28% men) were identified with anaemia, 27,524 (40% men) with changes in bowel habit and 44,741 (48% men) with rectal bleeding. For each cohort, the absolute risk rose with increasing age, and men were twice as likely to develop colorectal cancer. The PPV for developing colorectal cancer in the subsequent 12 months in those aged 60-69 years with anaemia was 3.02% for men, 1.38% for women; with changes in bowel habit 6.89% for men, 2.42% for women; and with rectal bleeding was 5.99% for men, 3.50% for women. A combination of any two signs and symptoms doubled the risk of an underlying cancer. In UK general practice, men are less likely to present with symptoms and signs of colorectal cancer compared with women, but after investigation are much more likely to have a colorectal cancer diagnosed. This should be taken into account in guidelines for referral.

Intra-vascular glucocorticoid metabolism as a modulator of vascular structure and function.

The ability of glucocorticoids to directly alter arterial function, structure and the inflammatory response to vascular injury may contribute to their well-established link with the development of cardiovascular disease. Recent studies have emphasised the importance of tissue-specific regulation of glucocorticoid availability by the 11 beta-hydroxysteroid dehydrogenase (11HSD) isozymes, which inter-convert active glucocorticoids and their inactive metabolites. The expression of both type 1 and type 2 11HSDs in the arterial wall suggests that prereceptor metabolism of glucocorticoids may have a direct impact on vascular physiology. Indeed there is evidence that 11HSDs influence glucocorticoid-mediated changes in vascular contractility, vascular structure, the inflammatory response to injury and the growth of new blood vessels. Hence, inhibition of 11HSD isozymes may provide a novel therapeutic target in vascular disease.

5-Alpha reductase inhibition provides superior benefits to alpha blockade by preventing AUR and BPH-related surgery.

OBJECTIVES: This analysis examines the relative effectiveness of current medical therapies for BPH in preventing AUR, AUR-related catheterisation and surgery in real-life clinical practice. METHODS: This is a retrospective analysis of observational data from the General Practice Research Database (UK) (GPRD). The cohort contains 4500 patients experiencing BPH or lower urinary tract symptoms strongly suggestive of BPH, aged over 50 years, who were prescribed a 5ARI (finasteride) or an alpha-blocker (alfuzosin, doxazosin, indoramin, prazosin, tamsulosin, terazosin) as their first BPH treatment between 1996 and 1999 inclusive. Cox regression and competing risks analyses, adjusted for age and year of first treatment, followed patients from the start of their first BPH treatment to AUR, catheterisation or surgery, or censoring. RESULTS: Patients prescribed an alpha-blocker were significantly more likely to experience AUR (hazard ratio 2.32, 95%CI 1.37, 3.94) or surgery (hazard ratio 1.78, 95%CI 1.30, 2.44) than patients prescribed a 5ARI. These differences were sustained with sensitivity analyses. CONCLUSION: Real-life clinical practice shows that significantly fewer BPH patients prescribed a 5ARI experienced serious complications associated with the progression of BPH compared with those prescribed an alpha-blocker.

Antibiotic failure in the treatment of urinary tract infections in young women.

Urinary tract infections (UTIs) are a common problem in young women. The aim of this study was to describe the pattern of antibiotic prescribing to young women presenting with new UTIs and to investigate the proportion who required further treatment if prescribed antibiotics. A secondary aim was to investigate whether the likelihood of treatment failure varied between different antibiotics and, in the case of trimethoprim (the antibiotic most frequently prescribed for UTIs) between prescriptions of different duration. The study included all women aged 15-44 years registered on the UK General Practice Research Database. All diagnoses of UTI or cystitis with an associated prescription for an antibiotic were identified. A further prescription of an antibiotic within 28 days was taken to indicate failure of the initial treatment. Overall, 14% of 75045 newly treated patients with UTI received a second antibiotic within 28 days. Older women, aged 35-44, pregnant patients and those with diabetes were significantly more likely to require further treatment. With trimethoprim as the reference antibiotic, after 28 days patients prescribed amoxicillin were significantly more likely to require a second course of antibiotics. Those prescribed co-trimoxazole were significantly less likely to require further treatment. In each case the difference in failure rate was small and may be of little clinical significance. There was no significant difference between trimethoprim and nitrofurantoin, norfloxacin, ciprofloxacin or the cephalosporins. Three-day prescriptions for trimethoprim appeared as effective as those for 5 or 7 days. This study gives some observational evidence of the effectiveness of antibiotic prescribing in young women with UTIs and shows that between 12% and 16% of patients will return within 28 days for further treatment, irrespective of the antibiotic prescribed initially.

A CCR5-dependent novel mechanism for type 1 HIV gp120 induced loss of macrophage cell surface CD4.

Type 1 HIV gp120 is especially effective in disrupting immune cell function because it is able to cause dysregulation of both infected and uninfected cells. We report a novel CCR5-dependent mechanism of gp120-induced CD4 loss from macrophages. An M-tropic gp120, using CCR5, is able to induce 70% loss of cell surface CD4 from macrophages within an hour. This cell surface CD4 loss is more substantial and rapid than the 20% loss observed with T-tropic gp120(IIIB) by 3 h. The rapid and substantial CD4 loss induced by M-tropic gp120 is not observed on macrophages homozygous for the ccr5Delta32 mutation, which fail to express cell surface CCR5. We have used confocal imaging to show that gp120 and CD4 are internalized together by a process resembling receptor-mediated endocytosis, and that both proteins enter HLA-DR containing compartments of the macrophage. We have also shown by semiquantitative RT-PCR that, in response to CD4 loss from the cell surface, mRNA for CD4 is up-regulated and the intracellular pool of CD4 increases. CCR5 mRNA levels are also increased. It is proposed that internalization of self and viral protein and increased pools of intracellular CD4 could modulate Ag presentation efficiencies and have implications for the induction and maintenance of both productive immune responses and self-tolerance.

Lower urinary tract symptoms suggestive of benign prostatic obstruction--Triumph: the role of general practice databases.

The Triumph project aims to document the current management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in general practice and to assess the effectiveness of the initial treatment options used. The first phase of the project will consider existing data sources in primary care. A patient's medical record will contain most, if not all, clinically relevant information, and databases combining the records from a network of computerised general practices can provide longitudinal data for complete populations, linking prescribing records to clinical information on disease progression and outcomes for individual patients. Database research can provide rapid information and offers the ability to conduct studies on a scale that would previously have been prohibited by both time and expense. Within the Triumph project, the THALES, General Practice Research Database (GPRD) and Integrated Primary Care Information (IPCI) databases are, or will be, used to examine the current management of LUTS/BPH in France, the UK and the Netherlands respectively. Preliminary results from the UK General Practice Research Database (GPRD) showed that LUTS/BPH incidence increased linearly from the ages of 45 to 85 years (r(2) = 0.992) and prevalence increased from 3.5% to 35% for men in their late 40s and 80s respectively. With treatment failure defined as a change to another medical therapy, catheterisation or prostatic surgery, and accounting for age and year variation, patients receiving the older alpha(1)-blockers (indoramin and prazosin) appeared to fail significantly earlier than those receiving finasteride. There was no significant difference between finasteride and the newer alpha(1)-blockers (tamsulosin, alfuzosin, terazosin and doxazosin). Patterns of changes between products from the THALES database in France were broadly similar to those seen in the UK.

How do symptoms indicative of BPH progress in real life practice? The UK experience.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are usually, but not exclusively associated with benign prostatic hyperplasia (BPH). Using a population identified from the UK General Practice Research Database (GPRD), we describe the changes in the management of LUTS/BPH and assess the effectiveness of medical therapy between 1992 and 1998. METHODS: 61,364 men with LUTS/BPH and without a record of prostatic cancer were identified on the database. 14,195 were treated with an alpha1-blocker or finasteride. Treatment failure was defined as prostatic surgery, catheterisation or a switch in medical therapy. RESULTS: LUTS/BPH incidence increased linearly from the age of 45 to 85 years (r2 = 0.992) and prevalence increased from 3.5% to 35% for men in their late 40s and 80s respectively. Prostatectomy rates increased linearly from the age of 50 to 80 years (r2 = 0.984). Between 1992 and 1998, total treated-patient time had increased 3-fold, patients have been medically treated earlier and have increasingly been prescribed the LUTS/BPH-specific treatments finasteride, tamsulosin and alfuzosin in comparison to older treatments (indoramin, prazosin). In parallel, there has been a progressive increase in the interval between first diagnosis and prostatic surgery, and this interval is significantly longer for medically treated patients than those receiving no medical therapy. The intervals between the start and failure of medical therapy were significantly shorter for patients receiving indoramin and prazosin than for those receiving specific LUTS/BPH treatments. CONCLUSIONS: Between 1992 and 1998 there has been a significant lengthening of the period between first diagnosis of LUTS/BPH and surgery. This postponement of surgery is associated with earlier treatment and the increased use of specific LUTS/BPH treatments that appear more effective than older products in delaying treatment failure.

Repeated use of hormonal emergency contraception by younger women in the UK.

A cohort of women aged 14-29 in 1993 was identified from the General Practice Research Database and followed up for a period of 4 years. Patient files were searched for evidence of use of emergency contraception and regular contraception. Of the 95 007 women, 15 105 (16%) had received emergency contraception during the study period (an average of 5% per annum). There was a small year on year increase in uptake of emergency contraception between 1994 and 1997. Only 4% of emergency contraception users received emergency contraception more than twice in any year. More than 70% of those who had no previous record of use of regular contraception had used regular contraception within 1 year of using emergency contraception. Teenagers were more likely than other age groups to use emergency contraception, to be repeat users of emergency contraception and to fail to start regular contraception after first use of emergency contraception until later in the study period. These results disprove the notion of widespread repeated use of emergency contraception. They show that provision of an emergency contraception service does not result in failure to initiate regular contraception or abandonment of regular contraception; rather they show many women using regular contraception for the first time after use of emergency contraception.

Patterns of prescription of PC4 by general practitioners in England and Wales.

OBJECTIVE: To study the pattern of general practitioner prescribing of PC4, the most commonly used method of hormonal emergency contraception, in England and Wales. METHOD: The UK General Practice Research Database was used to identify, from a total population of 4.2 million people on the lists of contributing practices, all women aged 10-44 years who were prescribed PC4. Rates of prescribing were calculated to produce rates over time by age group, by day of week and month of year, and by region. RESULTS: The rate for PC4 prescribing rose from about 1.5 per 1,000 women per month in 1992 to about 3.0 in 1995, then remained relatively constant until 1998. Rates were highest among 15-19-year-old women and next highest among those aged 20-24 years. Rates were higher in Wales than in each of the English regions. Excesses of prescribing took place in the summer months and between Saturdays and Mondays. CONCLUSION: Reasons for the increase in PC4 prescribing rates in the early years of the study are unclear, although increasing knowledge of the technique among the population may have contributed. There was no evidence of an increase in prescribing following the pill scare of October 1995, although there was an increase some months earlier. The concentration of requests at weekends suggests the need for weekend access to emergency contraception. The summer peak may also indicate a heightened need in holiday areas at that time.

Ultrasonic detection of parathyroid adenomas.

High-resolution real time sonography was used to evaluate patients with suspected primary hyperparathyroidism. A total of 12 consecutive patients was scanned pre-operatively. The sensitivity of the procedure was 92% and the specificity 97%. In our hospital sonography is the procedure of choice for localizing enlarged parathyroid glands prior to surgical exploration.

Technical training in surgery: the trainee's view.

A questionnaire designed to investigate the technical training of general surgical trainees was distributed throughout Scotland. A total of 222 questionnaires were sent out and 179 (81 per cent) were returned. Of the responders, 38 per cent felt that the overall operative workload was too small and the majority thought that there was too little emphasis on supervised operating. Two-thirds of trainees were generally satisfied with the amount of unsupervised operating, although a substantial proportion (21 per cent) sometimes felt out of their depth when performing delegated emergency operations. Few had attended craft workshops or travelled to other centres, but of those who had, most considered both activities to be very useful. Photographic atlases and videos were not generally felt to be of great value by those who had used them. The majority of trainees did not believe that research activity had interfered excessively with their technical training.

Endoscopic haemostasis in non-variceal upper gastrointestinal haemorrhage using adrenaline injection.

Fifteen patients found to have active arterial bleeding from non-variceal lesions at upper gastrointestinal endoscopy were treated with local injection of 1/10,000 adrenaline. Permanent haemostasis was obtained in 13 patients, and two required emergency surgery for rebleeding. Adrenaline injection is an effective, simple method of endoscopic haemostasis.