The history of adoption of hepatic resection for metastatic colorectal cancer: 1984-95.

BACKGROUND: Liver resection for metastatic colorectal cancer became established without randomized trials. Proponents of surgical resection point out 5-year survival approaching 50% whilst critics question how much of the apparent effect is due to patient selection. METHOD: A 2006 systematic review of reported outcomes provided the starting point for citation analysis followed by thematic analysis of the texts of the most cited papers. RESULTS: 54 reports from 1988 to 2002 cited 709 unique publications a total of 1714 times. The 15 most cited papers were explored in detail, and showed clear examples of duplicate reporting and overlapping data sets. Textual analysis revealed proposals for a randomized controlled trial, but this was argued to be unethical by others, and no trial was undertaken. CONCLUSIONS: This critical review reveals how the case for this surgery was made, and examines the arguments that influenced acceptance and adoption of this surgery.

Automating the monitoring of surgical site infections using variable life-adjusted display charts.

We describe a software tool specifically developed to support the monitoring and reporting of the occurrence of surgical site infections (SSI) in hospitals. The tool uses data collected routinely by a London teaching hospital as part of its infection surveillance system, which includes post-discharge follow-up. Based on these data, the tool is used to generate graphs showing cumulative infections over time and variable life-adjusted display (VLAD) charts that account for the expected specialty average infection risk. The user can select, along with other options, the definition of infection used in the preparation of the graphs. Using an illustrative example of SSI monitoring in orthopaedic surgery, we demonstrate the tool and its intended use to trigger further scrutiny rather than draw firm conclusions. We show that the tool has the ability to generate departmental debate, which should ultimately lead to the increased safety of surgical patients. We recommend adopting the tool and VLAD charts wherever surgical site surveillance is continuous.

Clinical reports of pulmonary metastasectomy for colorectal cancer: a citation network analysis.

INTRODUCTION: Pulmonary metastasectomy for colorectal cancer is a commonly performed and well-established practice of ∼50 years standing. However, there have been no controlled studies, randomised or otherwise. We sought to investigate the evidence base that has been used in establishing its status as a standard of care. METHODS: Among 51 papers used in a recent systematic review and quantitative synthesis, a citation network analysis was performed. A total of 344 publications (the 51 index papers and a further 293 cited in them) constitute the citation network. RESULTS: The pattern of citation is that of a citation cascade. Specific analyses show the frequent use of historical or landmark papers, which add authority. Papers expressing an opposing viewpoint are rarely cited. CONCLUSIONS: The citation network for this common and well-established practice provides an example of selective citation. This pattern of citation tends to escalate belief in a clinical practice even when it lacks a high-quality evidence base and may create an impression of more authority than is warranted.

A simulation study of the winter bed crisis.

The winter bed crisis is a cyclical phenomenon which appears in British hospitals every year, two or three weeks after Christmas. The crisis is usually attributed to factors such as the bad weather, influenza, older people, geriatricians, lack of cash or nurse shortages. However, a possible alternative explanation could be that beds within the hospital are blocked because of lack of social services for discharge of hospital patients during the Christmas period. Adopting this explanation of why the bed crisis occurs, the problem was considered as a queuing system and discrete event simulation was employed to evaluate the model numerically. The model shows that stopping discharges of rehabilitating patients for 21 days accompanied by a cessation of planned patients for 14 days precipitate a bed crisis when the planned admissions recommence. The extensive "what-if" capabilities of such models could be proved to be crucial to the designing and implementation of possible solutions to the problem.

Antihypertensive drugs and the risk of idiopathic aplastic anaemia.

AIMS: A recent report has raised concern that nifedipine may be associated with an increased risk of aplastic anaemia. This large population-based study evaluated the risk of idiopathic aplastic anaemia in users of calcium channel blockers compared with that of other antihypertensive drugs. METHODS: The study was based on information derived from the General Practice Research Database. We conducted a follow-up study with a nested case-control analysis of 322 448 subjects who received antihypertensive drugs. Cases were people who had a first-time diagnosis of aplastic anaemia during January 1, 1988 through September 30, 1997. The risk estimate of aplastic anaemia was calculated for all antihypertensive drugs. For the nested case-control analysis, six controls were matched to each case on age, sex and general practice attended. Odds ratios compared the risk of idiopathic aplastic anaemia for all antihypertensive drugs relative to nonusers. RESULTS: There were 13 cases of newly diagnosed idiopathic aplastic anaemia. The estimated risk of aplastic anaemia per 100 000 users was 0.8 (95% CI 0.1, 4.7) for calcium channel blockers, 1.4 (95% CI 0.5, 4.1) for beta-adrenoceptor blockers, 2.3 (95% CI 0.6, 8.6) for angiotension-converting enzyme (ACE) inhibitors and 5.9 (95% CI 1.6, 21.5) for users of other antihypertensive drugs. In the case-control analysis of 13 cases and 77 controls, the odds ratio was 0.3 (95% CI 0.02, 3.3) for calcium channel blockers, 0.5 (95% CI 0.1, 2.5) for beta-adrenoceptor blockers, 0.7 (95% CI 0.1, 5.6) for ACE inhibitors, 1.2 (95% CI 0.1, 11.8) for users of other antihypertensive drugs and 0.7 (95% CI 0.1, 7.2) for users of multiple drugs with a calcium channel blocker compared with nonusers. CONCLUSIONS: The present study suggests that the use of calcium channel blockers is not associated with an increased risk of aplastic anaemia.

Measuring and modelling surgical bed usage.

Surgical departments treat two groups of inpatients--the simple and the complex--consequently a single average fails to describe the use being made of the occupied beds. Using decision support techniques, we show why indicators such as the average length, the average occupancy and the average admissions mislead. Furthermore, by analysing the fluctuating pattern of weekly admissions we show how weekends and the Christmas holiday periods impact on bed usage. Next, we demonstrate that flow process models can be used to describe how the in-patient workload concerns two groups of patients. On an average day, 71.4% of the beds contained patients who will have an average (exponential) stay of 4.8 days, and the other beds, 28.6%, contain patients who will have an average (exponential) stay of 22.8 days. The article concludes by demonstrating the short and long-term impact on daily admissions of a 10% change in four different parameters of the model. The data used come from a surgical department in Adelaide, as UK data sets report finished consultant episodes rather than completed in-patient spells.

Risk of idiopathic venous thromboembolism in users of progestagens alone.

Overall, there was a modest, non-significant, positive association between exposure to progestagens alone and venous thromboembolism (VTE). There was no effect with progestagens alone used for contraception, whereas there was a substantial association with the higher dose progestagens used for other reasons.

The risk of venous thromboembolism in users of postcoital contraceptive pills.

Postcoital contraceptive pills (PCP) have recently been approved for use as emergency contraception in the United States. The objective of this study was to assess the risk of idiopathic venous thromboembolism (VTE) in relation to exposure to PCP, and to better quantify the risk of idiopathic VTE associated with current oral contraceptive (OC) use and pregnancy. A population-based cohort study with a nested case-control analysis was conducted using women from the General Practice Research Database. There were no women with an outcome of idiopathic VTE with current exposure to PCP. The incidence rates for various exposures were 3.0/100,000 person-years for the unexposed, 5.3/100,000 person-years for second generation OC, 10.7/100,000 person-years for third generation OC, and 15.5/100,000 person-years in pregnant (or postpartum) women. The relative risk estimates were 1.7 (95% CI 0.3-10.5) for second generation OC, 4.4 (95% CI 1.0-18.7) for third generation OC, and 6.3 (95% CI 1.2-33.5) for pregnancy. Short-term use of PCP is not associated with a substantially increased risk for developing VTE.

PIP: A population-based cohort study with a nested case-control analysis was conducted to assess the risk of idiopathic venous thromboembolism (VTE) in relation to exposure to postcoital contraceptive pills (PCP) and to better quantify the risk of idiopathic VTE associated with current oral contraceptive (OC) use and pregnancy. The subjects were women less than 50 years of age who received PCP prescriptions at some time between January 1, 1989, and October 31, 1996. All subjects in the cohort of PCP users had a computer-recorded diagnosis from the General Practice Research Database. The results of the study indicate that there were no women currently exposed to PCP who had an outcome of idiopathic VTE. The incidence rates for various exposures were 3.0/100,000 person-years for those unexposed, 5.3/100,000 person-years for second-generation OCs, 10.7/100,000 person-years for third-generation OCs, and 15.5/100,000 person-years for pregnant (or postpartum) women. The relative risk estimates were 1.7 (95% CI, 0.3-10.5) for second-generation OCs and 4.4 (95% CI, 1.2-33.5) for pregnancy. Thus, the risk of VTE attributable to PCP is not substantially higher than it is for the risk for traditional OCs, despite the higher content of both estrogen and progesterone present in PCP.

Antibiotics and risk of subsequent first-time acute myocardial infarction.

CONTEXT: Increasing evidence supports the hypothesis of a causal association between certain bacterial infections and increased risk of developing acute myocardial infarction. If such a causal association exists, subjects who used antibiotics active against the bacteria, regardless of indication, might be at lower risk of developing acute myocardial infarction than nonusers. OBJECTIVE: To determine whether previous use of antibiotics decreases the risk of developing a first-time acute myocardial infarction. DESIGN: Population-based case-control analysis. SETTING: The United Kingdom-based General Practice Research Database comprising 350 general practices. PATIENTS: A total of 3315 case patients aged 75 years or younger with a diagnosis of first-time acute myocardial infarction between 1992 and 1997 and 13139 controls without myocardial infarction matched to cases for age, sex, general practice attended, and calendar time. MAIN OUTCOME MEASURES: Use of antibiotics among those who did or did not have a first-time acute myocardial infarction. RESULTS: Cases were significantly less likely to have used tetracycline antibiotics (adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.55-0.90) or quinolones (adjusted OR, 0.45; 95% CI, 0.21-0.95). No effect was found for previous use of macrolides (primarily erythromycin), sulfonamides, penicillins, or cephalosporins. CONCLUSIONS: The findings from this large case-control analysis provide further, albeit indirect, evidence for an association between bacterial infections with organisms susceptible to tetracycline or quinolone antibiotics and the risk of acute myocardial infarction. These results of preliminary nature should stimulate more research to further explore the role of infections in the etiology of acute myocardial infarction.

A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation.

BACKGROUND: Recent case reports suggest that a combination of the appetite suppressants fenfluramine and phentermine is associated with an increased risk of cardiac-valve regurgitation. There are also reports of valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for more than three months. METHODS: We conducted a population-based follow-up study and a nested case-control analysis of 6532 subjects who received dexfenfluramine, 2371 who received fenfluramine, and 862 who received phentermine to assess the risk of a subsequent clinical diagnosis of a valvular disorder of uncertain origin. For comparison, we identified a group of 9281 obese subjects who had not taken appetite suppressants who were matched to the treated subjects for age, sex, and weight. All subjects were free of diagnosed cardiovascular disease at the start of follow-up. The average duration of follow-up for all subjects was about four years. RESULTS: There were 11 cases of newly diagnosed idiopathic valvular disorders, 5 after the use of dexfenfluramine and 6 after the use of fenfluramine. There were six cases of aortic regurgitation, two cases of mitral regurgitation, and three cases of combined aortic and mitral regurgitation. There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only phentermine. The five-year cumulative incidence of idiopathic cardiac-valve disorders was 0 per 10,000 subjects among those who had not taken appetite suppressants (95 percent confidence interval, 0 to 15.4) and among those who took phentermine alone (95 percent confidence interval, 0 to 76.6), 7.1 per 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four months (95 percent confidence interval, 3.6 to 17.8; P=0.02 for the comparison with subjects who had not taken appetite suppressants), and 35.0 per 10,000 subjects among those who received either of these medications for four or more months (95 percent confidence interval, 16.4 to 76.2; P<0.001). CONCLUSIONS: The use of fenfluramine or dexfenfluramine, particularly for four months or longer, is associated with an increased risk of newly diagnosed cardiac-valve disorders, particularly aortic regurgitation.

The risk of seizures associated with tramadol.

We conducted a study of the risk of idiopathic incident seizures among users of tramadol derived from data present in the General Practice Research Database based in the United Kingdom for 1994-1996. We used a nested case-control study design, comparing risks of idiopathic incident seizures during exposed and unexposed times among patients who had ever taken tramadol using a 90-day follow-up. Among the 10,916 subjects, we identified 17 cases of idiopathic seizures, 11 of which were definite and 6 possible. None of the patients was exposed to tramadol alone in the prior 90 days. Eight patients were exposed to opiates, five to both tramadol and opiates, three to other analgesics, and one to no analgesics. We found no increased risk of idiopathic incident seizures associated with exposure to tramadol alone. Thus seizures seem rarely attributable to the agent.

Acute respiratory-tract infections and risk of first-time acute myocardial infarction.

BACKGROUND: There is growing interest in the role of infections in the aetiology of acute myocardial infarction (AMI). We undertook a large, population-based study to explore the association between risk of AMI and recent acute respiratory-tract infection. METHODS: We used data from general practices in the UK (General Practice Research Database). Potential cases were people aged 75 years or younger, with no history of clinical risk factors, who had a first-time diagnosis of AMI between Jan 1, 1994, and Oct 31, 1996. Four controls were matched to each case on age, sex, and the practice attended. The date of the AMI in the case was defined as the index date. For both cases and controls the date of the last respiratory-tract infection before the index date was identified. We also did a case-crossover analysis of cases who had an acute respiratory-tract infection either before the index date or before an arbitrarily chosen date (1 year before AMI). FINDINGS: In the case-control analysis of 1922 cases and 7649 matched controls, significantly more cases than controls had an acute respiratory-tract infection in the 10 days before the index date (54 [2.8%] vs 72 [0.9%]). The odds ratios, adjusted for smoking and body-mass index, for first-time AMI in association with an acute respiratory-tract infection 1-5, 6-10, 11-15, or 16-30 days before the index date (compared with participants who had no such infection during the preceding year) were 3.6 (95% CI 2.2-5.7), 2.3 (1.3-4.2), 1.8 (1.0-3.3), and 1.0 (0.7-1.6); (test for trend p<0.01). The case-crossover analysis showed a relative risk of 2.7 (1.6-4.7) for AMI in relation to an acute respiratory-tract infection in the 10 days before the index date. INTERPRETATION: Our findings suggest that in people without a history of clinical risk factors for AMI, acute respiratory-tract infections are associated with an increased risk of AMI for a period of about 2 weeks. We cannot, however, completely exclude the possibility of misdiagnosis bias, if prodromal symptoms of AMI were mistaken for respiratory-tract infection.

A study of the relation of exposure to quinolones and suicidal behaviour.

AIMS: To investigate the concern, raised by spontaneous reports received by the German regulatory authorities, that use of quinolone antibiotics may increase the risk for suicide and other suicidal behaviours. METHODS: We carried out a nested case-control study using the General Practice Research Database (GPRD). We compared the risk of suicidal behaviours among users of quinolones, other antibiotics and no antibiotics. RESULTS: From January 1, 1991 through April 30, 1995 we identified 348 cases of suicide, attempted suicide, or suicidal ideation and 808 controls. Compared with controls, cases who had received a prescription for a quinolone in the 30 days prior to the event had an adjusted relative risk (RR) estimate of 1.5 (95% CI 0.4-6.3) for any suicidal behaviour. Cases who had filled a prescription for a quinolone in the 31 to 180 days prior to their event had an adjusted RR estimate of 0.8 (95% CI 0.4-1.7) compared with controls. Cases who used other antibiotics in the 30 days prior to the event conferred an adjusted RR estimate of 1.1 (95% CI 0.6-2.2), and 0.9 (95% CI 0.6-1.3) for exposure in the 31 to 180 days prior to the event. The results were not materially different when suicide, suicide attempt, and suicidal ideation were analyzed separately. CONCLUSIONS: We conclude that there is no material increased risk of suicidal behaviours for use of quinolone antibiotics compared with non-use or use of other antibiotics.

A simulation modelling approach to evaluating length of stay, occupancy, emptiness and bed blocking in a hospital geriatric department.

The flow of patients through geriatric hospitals has been previously described in terms of acute (short-stay), rehabilitation (medium-stay), and long-stay states where the bed occupancy at a census point is modelled by a mixed exponential model using BOMPS (Bed Occupancy Modelling and Planning System). In this a patient is initially admitted to acute care. The majority of the patients are discharged within a few days into their own homes or through death. The rest are converted into medium-stay patients where they could stay for a few months and thereafter either leave the system or move on to a long-stay compartment where they could stay until they die. The model forecasts the average length of stay as well as the average number of patients in each state. The average length of stay in the acute compartment is artificially high if some would-be long-term patients are kept waiting in the short-stay compartment until beds become available in long-stay (residential and nursing homes). In this paper we consider the problem as a queueing system to assess the effect of blockage on the flow of patients in geriatric departments. What-if analysis is used to allow a greater understanding of bed requirements and effective utilisation of resources.

An analysis of admission, discharge and bed occupancy of stroke patients aged 65 and over in English hospitals.

Stroke illness is a common problem in the UK. Factors such as incidence, age, and ethnicity have already been shown to affect admission patterns and discharge outcomes. Our analysis of an English Hospital Episode Statistics database shows that weekends and public holidays also influence the admission and discharge patterns of elderly stroke patients. We discuss the possible reasons for this.

Antihypertensive drugs and fatal myocardial infarction in persons with uncomplicated hypertension.

We conducted a case-control study to evaluate the risk of fatal myocardial infarction in otherwise healthy treated hypertensive subjects according to the type of the antihypertensive drug used. The study encompassed 207 cases and 409 controls matched to cases on age, sex, and general practice. Compared with beta-blocker users, the matched relative risk estimates for fatal myocardial infarction, adjusted for recent blood pressure, body mass index, smoking, duration of hypertension, and prior use of other antihypertensive drugs, were 0.7 [95% confidence interval (CI) = 0.4-1.2] for angiotensin-converting enzyme inhibitor users, 0.9 (95% CI = 0.5-1.5) for calcium channel blocker users, and 0.7 (95% CI = 0.4-1.2) for diuretic users.