Frequent loss of the BLID gene in early-onset breast cancer.

The BH3-like motif-containing inducer of cell death (BLID) is an intronless gene localized on 11q24.1. Loss of that region has frequently been reported in early-onset breast cancer and is significantly associated with poor prognosis and reduced survival. Downregulation of BLID is associated with younger age, triple-negative phenotype, and reduced disease-free and overall survival of breast cancer patients. In this study, we investigated allelic loss of BLID in breast tumor specimens from 78 women with invasive breast cancer using 2 dinucleotide polymorphic markers closely linked to the BLID gene (no intragenic marker for BLID is available). Seventy-three cases were informative. Overall, loss of heterozygosity (LOH) at the BLID locus was detected in 32% of the informative cases (23/73). However, in patients 40 years old and younger, LOH was detected in 50% of the cases (9/18). Patients aged 40 years and younger were significantly more likely to experience LOH than those aged 41-55 years (p = 0.04). Specifically, the odds of BLID loss for patients aged 40 years and younger were 3.7 times the odds of loss for patients aged 41-55 years (95% CI, 1.1-13). Our findings suggest a tumor suppressor role of the BLID gene in early-onset breast cancer.

Uncontrolled bleeding in surgical patients: the role of recombinant activated factor VIIa.

Recombinant activated factor VII (rFVIIa), developed and effective in managing inhibitors in haemophilia patients, is being widely used off-label as a "panhaemostatic agent" with ongoing controversy as to its benefits and risks in terms of controlling critical haemorrhage and improving patient outcomes. Current insights into haemostatic mechanisms have resulted in a better understanding of the central role of FVII/FVIIa and tissue factor in the localization and initiation of haemostasis. There is a plethora of case reports and series published on the use of rFVIIa in critical life-threatening haemorrhage and in perioperative settings associated with significant blood loss or the potential for catastrophic haemorrhage. Additionally, the literature is replete with reviews for the use of rFVIIa in various clinical settings, but there is a dearth of good evidence from randomized controlled trials for efficacy. Safety, especially from the thrombogenicity perspective, has been a major issue, but turns out to be less of a concern with thrombotic potential needing to be weighed against the anticipated benefits. Although there is some clinical trial and observational data supporting efficacy it has been difficult to recommend clear clinical practice guidelines, especially as clinical outcome data in terms of morbidity and mortality is limited. Some of the best evidence relates to reduction in allogeneic blood transfusion requirements. This in itself is important and probably clinically relevant in view of the accumulating evidence that allogeneic blood transfusion is an independent risk factor for poorer clinical outcome. It is unlikely that there will be adequate randomized clinical trials to better answer the question of efficacy, thus making data from registries of greater importance. Indeed, the process of establishing efficacy, safety and regulation of a therapeutic that is increasingly used off-label is not without significant difficulties.

Results from the Scottish National HAI Prevalence Survey.

A national point prevalence survey was undertaken over the period of one calendar year in Scotland from October 2005 to October 2006. The prevalence of healthcare-associated infection (HAI) was 9.5% in acute hospitals and 7.3% in non-acute hospitals. The highest prevalence of HAI in acute hospital inpatients was found in the following specialties: care of the elderly (11.9%), surgery (11.2%), medicine (9.6%) and orthopaedics (9.2%). The lowest prevalence was found in obstetrics (0.9%). The most common types of HAI in acute hospital inpatients were: urinary tract infections (17.9% of all HAI), surgical site infections (15.9%) and gastrointestinal infections (15.4%). In non-acute hospitals one in ten inpatients in two specialties (combined) - medicine (11.4%) and care of the elderly (7.8%) - was found to have HAI, and one in 20 inpatients in psychiatry (5.0%) had HAI. In non-acute hospital patients, urinary tract infections were frequent (28.1% of all HAI) and similarly skin and soft tissue infection (26.8% of all HAI). When combined, these two HAI types affected 4% of all the inpatients in non-acute hospitals. This is the first survey of its kind in Scotland and describes the burden of HAI at a national level.

A study of telephone screening and direct observation of surgical wound infections after discharge from hospital.

Post-discharge surveillance of surgical site infection is necessary if accurate rates of infection following surgery are to be available. We undertook a prospective study of 376 knee and hip replacements in 366 patients in order to estimate the rate of orthopaedic surgical site infection in the community. The inpatient infection was 3.1% and the post-discharge infection rate was 2.1%. We concluded that the use of telephone interviews of patients to identify the group at highest risk of having a surgical site infection (those who think they have an infection) with rapid follow-up by a professional trained to diagnose infection according to agreed criteria is an effective method of identifying infection after discharge from hospital.

Clinician-led surgical site infection surveillance of orthopaedic procedures: a UK multi-centre pilot study.

The UK Department of Health established the Healthcare-associated Infection (HAI) Surveillance Steering Group in 2000 to develop a strategy for implementing a national programme for HAI surveillance in National Health Service trusts. A subgroup of this committee examined the surveillance of surgical site infections following orthopaedic surgery. This group oversaw a pilot scheme that was set up in 12 hospitals around the UK to explore the feasibility of implementing a system of surveillance that engaged clinical staff in its operation, provided a process for continuous data collection and could be maintained as part of routine hospital operation over time. A minimum data set was established by the subgroup, and Centers for Disease Control and Prevention (CDC) definitions of infection were used. By March 2003, the surveillance had been undertaken continuously in 11 sites for one to two years, depending on the date of implementation. Only one hospital had ceased data collection. The information was collected mainly by clinical staff, with support and co-ordination usually provided by infection control teams. Data on more than 5400 procedures were available for analysis for four core procedures: arthroplasty of the hip and knee; hemi-arthroplasty of the hip; and internal fixation of trochanteric fractures of the femur. The data set permitted the calculation of risk-adjusted rates, allowing comparisons between hospitals and within a hospital over time. The methodology enhanced clinical ownership of the surveillance process, re-inforced infection control as the responsibility of all staff, and provided timely feedback and local data analysis. The use of CDC definitions permitted international comparisons of the data.

Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data.

OBJECTIVE: To look for evidence of a relation between antibiotic resistance and prescribing by general practitioners by analysis of prescribing at both practice and individual patient level. DESIGN: Repeated cross-sectional study in 1995 and 1996. SETTING: 28 general practices in the Ninewells Hospital laboratory catchment area, Tayside, Scotland. SUBJECTS REVIEWED: 8833 patients registered with the 28 practices who submitted urine samples for analysis. MAIN OUTCOME MEASURES: Resistance to trimethoprim in bacteria isolated from urine samples at practice and individual level simultaneously in a multilevel model. RESULTS: Practices showed considerable variation in both the prevalence of trimethoprim resistance (26-50% of bacteria isolated) and trimethoprim prescribing (67-357 prescriptions per 100 practice patients). Although variation in prescribing showed no association with resistance at the practice level after adjustment for other factors (P = 0.101), in the multilevel model resistance to trimethoprim was significantly associated with age, sex, and individual-level exposure to trimethoprim (P < 0.001) or to other antibiotics (P = 0.002). The association with trimethoprim resistance was strongest for people recently exposed to trimethoprim, and there was no association for people with trimethoprim exposure more than six months before the date of the urine sample. DISCUSSION: Analysis of practice level data obscured important associations between antibiotic prescribing and resistance. The results support efforts to reduce unnecessary prescribing of antibiotics in the community and show the added value of individual patient data for research on the outcomes of prescribing.

Surgical site infection after groin hernia repair.

BACKGROUND: Post-discharge surveillance for 30 days is needed to determine the true incidence of surgical site infection (SSI). This study was undertaken to determine the incidence of, and risk factors for, SSI after hernia repair. METHODS: A total of 3150 patients who had undergone groin hernia repair in 32 Scottish hospitals were telephoned 10, 20 and 30 days after operation to screen for SSI. Patients who believed the wound to be infected were seen by a healthcare worker to confirm the diagnosis. Details of operations and risk factors were obtained by case-note review. RESULTS: One hundred and four patients (3.3 per cent) declined to give a contact telephone number, leaving 3046 patients who agreed to take part in the study. Some 108 patients (3.4 per cent) could not be contacted at any point, giving a response rate of 93.3 per cent. Complete data were available for 2665 patients (87.5 per cent); 140 (5.3 per cent) developed SSI and 57 (2.1 per cent) thought the wound infected but this was not confirmed by the healthcare worker. Patients given a prophylactic antibiotic had a lower incidence of SSI (P = 0.002), but neither increase in the American Society of Anesthesiologists grade of fitness for operation nor prolonged duration of operation was a significant risk factor for infection. CONCLUSION: SSI after hernia repair is common and large clinical trials are required to determine whether the use of prophylactic antibiotics reduces the incidence of infection.

Telephone call contact for post-discharge surveillance of surgical site infections. A pilot, methodological study.

Accurate determination of superficial surgical-site infection (SSI) requires post-discharge surveillance (PDS) for up to 30 days. To be useful for regional or national audit the method must be effective, inexpensive, and acceptable to patients. We assessed the role of telephone calls to patients in PDS of SSI in 3150 patients in 32 Scottish hospitals undergoing groin hernia repair during one year. Overall, 104 (3.3%) patients opted out of the audit by declining to give a contact telephone number, 96 (3.0%) could not provide a personal telephone contact number, and 12 could not be contacted, a compliance rate of 93.3%. Two thousand, nine hundred and thirty-eight patients were contacted at one or all of the call points, i.e. 10, 20, or 30 days postoperatively, from a single call centre by medical records clerks, working to a piloted protocol. Contact data, including contact at all three time points are available on 2665 (84.6%) patients. All patients who believed their wound to be infected were seen by a healthcare worker (HCW) to confirm or refute the diagnosis. Of the 2665 patients in whom complete data are available, 140 (5.3%) patients developed confirmed wound infection and a further 57 (2.1%) thought their wound was infected, but this was not confirmed by the HCW. Patients appeared to welcome the concept of telephone contact. Methods for identifying all patients eligible for surveillance need to be improved. However, we believe this method of patient contact could be appropriate for PDS in regional or national audit.

Harmonisation of national influenza surveillance morbidity data from EISS: a simple index.

The European Influenza Surveillance Scheme is a collaboration with 18 member countries (2001/02) which monitors the activity and impact of influenza by collecting morbidity and virological data in primary care facilities throughout the winter season each year. Despite being in principle similar in the surveillance concept, the indicators used and observations made are very different. Different healthcare systems and organisational needs (eg a certificate of illness for the employer) influence the consultation behaviour. Furthermore, and partly as a result of differences in the healthcare systems, the definitions used for the numerator and denominator when calculating morbidity rates are different. Thus comparative interpretation of participating countries' morbidity data is extremely difficult. Reporting 'harmonisation' by using equivalent numerators and denominators is one option but is difficult to achieve in the short term. Moreover, several additional issues would need to be considered, for example, the need for continuity of surveillance and whether such steps would indeed result in direct comparability etc. A simple index was tested, through which the impact of influenza morbidity in any one year is compared with what is considered a 'usual' epidemic in that country. The index in principle describes numerically the extent to which the influenza-attributable excess morbidity in the current epidemic in each country is within, exceeds, or is less than a range typical for an influenza epidemic. In this pilot study, the usefulness of such an index is explored with the example of eight countries for the seasons 1999/2000 and 2000/01. A fine tuning of the methods has not yet been performed.

Chlamydia trachomatis in primary care: knowledge and practice in Glasgow.

A recent Department of Health report recommended the establishment of a selective screening programme for Chlamydia trachomatis infection. We report a survey which suggests that primary care clinicians may not yet be prepared for this task.

The public health applications of unlinked anonymous seroprevalence monitoring for HIV in the United Kingdom.

BACKGROUND: In order to monitor the epidemiology of human immunodeficiency virus (HIV), integrated national programmes of unlinked anonymous (blinded) HIV sero-surveys have taken place in the UK since 1990. METHODS: The programmes comprise multi-centre surveys primarily using specimens gathered routinely for screening groups of patients. All specimens are irreversibly unlinked from patient identifiers before being tested. RESULTS: The surveys have met their prime aim of providing at low cost minimally biased estimates of current HIV prevalence and trends in sentinel populations. The surveys have remained acceptable to professionals and the public, being successfully implemented without breech of their founding principles. The findings have had major public health applications, have influenced HIV policy and funding, been used for monitoring the spread of HIV, for targeting and evaluating health promotion and improving projections of severe HIV disease. The surveys have detected substantial prevalence rises and under-diagnosis of HIV which would otherwise have been unrecognised. The programmes' value is being increased by sub-typing HIV-1 isolates, capturing additional demographic information to detect spread among minority groups. The same specimens are used for monitoring other infections (initially hepatitis A, B and C). CONCLUSIONS: Monitoring HIV and other infections through unlinked anonymous HIV surveillance has become an integral essential part of national HIV and AIDS surveillance. Although it has unique applications the value of unlinked anonymous surveillance is maximized when used in conjunction with behavioural data, information from HIV and AIDS reporting, and behavioural data and surveillance for other sexually transmitted infections.

Gastrointestinal infections presenting in general practice in Scotland.

OBJECTIVES: To determine the incidence of gastrointestinal infections (GII) presenting to general practitioners (GPs) in Scotland, To record the demographic and clinical characteristics of persons presenting with GII, To determine the proportion and characteristics of GII investigated in the laboratory, To report on the microbiological aetiology of the GII. DESIGN: Descriptive epidemiological study. SETTING: Twenty three general practices in Scotland serving a total practice population of 152,471. SUBJECTS: Patients consulting their GPs for a 'gastrointestinal infection' which met the study case definition. RESULTS: These are presented for the 3872 patient consultations for GII between April 1996 and December 31st 1997 which met the survey case definition. The crude annual rate of new consultations recorded was 1.7 per 100 person years. The crude monthly consultation rate for new cases ranged between 11 and 18 per 10,000 patients. GPs notified 9% of the cases as 'food poisoning'. A request for microbiological testing of samples at the local laboratory for clinical reasons was documented for 34% of cases with diarrhoea. The study laboratory received faecal samples by post from 66% of these cases. About one in five of the samples tested revealed evidence of infection with a common gastrointestinal pathogen. The pathogens most frequently reported were Campylobacter sp and Salmonella sp. CONCLUSION: The incidence of consultations for GII in Scotland is similar to that recorded in a recent survey in England. The very low notification rate by GPs means that statutory notification by telephone or post is a poor basis for early warning of outbreaks. It is recommended that a pilot study of electronic notification using the NHS net is set up.

Epidemiology and treatment outcome of infection with antibiotic resistant strains of Neisseria gonorrhoeae in Scotland.

Antibiotic resistance in Neisseria gonorrhoeae occurs worldwide and may limit the efficacy of treatment. This study reports the epidemiology and treatment outcome for 125 episodes of infection with antibiotic resistant gonococci diagnosed in Scotland in 1996. Infections with penicillinase producing N. gonorrhoeae (PPNG) and/or high level plasmid mediated tetracycline resistant N. gonorrhoeae (TRNG) and isolates showing reduced susceptibility to ciprofloxacin were more likely to belong to an unusual serovar and have been acquired abroad by heterosexual intercourse than isolates showing chromosomal resistance to penicillin or tetracycline, which were more likely to belong to a common serovar and to have been acquired in the United Kingdom by homosexual intercourse. Among the 88 episodes of infection whose outcome was known initial treatment with an antibiotic to which the isolate was resistant failed in nine out of 16 infections and in three out of the 72 infections treated with an antibiotic to which the organism was sensitive. In the case of high level plasmid mediated resistance, treatment with an inappropriate antibiotic always resulted in failure. Continuous monitoring of treatment outcome is essential to guide clinicians in prescribing the most appropriate antibiotic for individual patients.

Surveillance of sexually transmitted infections in Scotland.

Applications of the surveillance of sexually transmitted infections (STIs) include setting priorities for and planning preventive and treatment services, evaluating interventions, and shaping research hypotheses. In Scotland routine data on STIs, (other t

Survival of adults with AIDS in the United Kingdom.

Accurate estimates of expected survival times and survival rates of AIDS patients are important both for estimating the prognosis of individuals and for monitoring the progress of the HIV/AIDS epidemic as new treatments are introduced. They are also needed for projecting future numbers of AIDS cases. Data on reported AIDS cases held at the PHLS AIDS Centre at the Communicable Disease Surveillance Centre and the Scottish Centre for Infection and Environmental Health confirmed the time, age, and reporting delay effects identified in earlier analyses of the United Kingdom AIDS database. The duration of survival after AIDS is diagnosed has improved since the epidemic began--median survival was 10.6 months in cases diagnosed before 1987 and has been at least 18.4 months in cases diagnosed each year since then. People who are diagnosed younger live longer--median survival fell from 21.6 months at age 15 to 29 to 12.6 months at age 45 or over. Delay in reporting AIDS cases adversely affects survival estimates for cases reported in recent years. Survival was longer in cases reported over a year after diagnosis of AIDS--23.7 months compared with 16.9 months in those reported less than a year after diagnosis. The experience of the hospital, measured by its cumulative AIDS caseload, was an important factor in the survival of men who have sex with men presenting with Kaposi's sarcoma alone or 'other' diagnoses--survival was shorter for cases reported from smaller centres. Men who have sex with men with Pneumocystis carinii pneumonia alone or other opportunistic infections alone who were known to be HIV positive before being diagnosed with AIDS had a shorter survival after being diagnosed than those who were unaware of their HIV infection. This supports the hypothesis that treatment for HIV infection and prophylaxis may extend the period before AIDS develops but reduce the period between developing AIDS and dying.

The costs and effectiveness of surveillance of communicable disease: a case study of HIV and AIDS in England and Wales.

BACKGROUND: In England and Wales, surveillance of communicable disease is carried out and co-ordinated by the Public Health Laboratory Service (PHLS). The surveillance of HIV infection and AIDS is undertaken by the PHLS AIDS Centre at the Communicable Disease Surveillance Centre (CDSC). Epidemiological data derived from surveillance are not, however, a free good: they are a resource with an associated opportunity cost and should therefore be open to economic appraisal alongside other users of health care resources such as medical interventions. This paper assembles information on the current surveillance of HIV and AIDS in England and Wales, and explores methods for performing an economic evaluation of such activities. METHODS: An examination of the cost and effectiveness of the PHLS AIDS Centre's epidemiological surveillance mechanisms for HIV and AIDS in England and Wales was undertaken. The total costs of each component of surveillance of HIV and AIDS in England and Wales were calculated. Two categories of cost were estimated: peripheral costs incurred by reporters in reporting AIDS cases or HIV infections or by laboratories in collecting samples; and central costs incurred by the PHLS AIDS Centre in processing and analysing incoming data. Using these cost data and information from a cost-effectiveness register, the additional health gains that would have to be obtained from surveillance to make the programme broadly cost-effective in comparison with other accepted uses of health service resources were then estimated. RESULTS: In the financial year 1993-1994 the total costs of surveillance were estimated to be 1.4 million pounds. To avoid being considered relatively cost-ineffective at least 3.5 infections per annum need to be averted. To be considered favourably cost-effective, approximately 9.5 infections per annum need to be averted. CONCLUSIONS: In 1993-1994, expenditure on surveillance of HIV and AIDS accounted for less than 1 per cent of the total allocation of resources to the National Health Service for all HIV and AIDS activities. Given these cost estimates, the number of infections which surveillance would have to contribute towards preventing in order to be considered cost-effective is low.