Clinical picture of peptic ulceration diagnosed endoscopically

Clinical features and laboratory data are presented for 100 patients with benign gastric ulceration and 150 patients with duodenal ulceration confirmed endoscopically in a district general hospital unit. Abdominal pain was the commonest indication for endoscopy, but one third of examinations were performed for acute gastrointestinal haemorrhage. Although the patients were selected by referral for endoscopy their clinical presentation, age, and sex distribution were similar to those reported in previous general surveys. There were no clinical features which clearly distinguished gastric from duodenal ulceration. However, of those with gastric ulceration younger patients more often had distal ulcers and presented with pain, while elderly subjects tended to have high lesser curve involvement and presented with haemorrhage. Moreover, all females presenting with haemorrhage were aged over 50 years, while 6% of males bleeding from gastric ulceration and 40% of males bleeding from duodenal ulceration were under this age. Anaemia when present, except in two premenopausal females, indicated either a recent acute gastrointestinal haemorrhage or a coexistent second diagnosis.     

Treatment of acute apoplexy at a medical department with a specialized rehabilitation unit

The aim of this retrospective study was to describe the occurrence of acute stroke and the effect of treatment measured as mortality, length of hospital stay and discharge to the home in a medical department with a specialized rehabilitation unit. During the period 1.9.1992-31.5.1995 110 patients were discharged to their own home after transient cerebral ischaemia, 23 after subarachnoid haemorrhage, 62 after documented intracerebral haemorrhage and 574 after acute stroke due to infarction or unknown cause. The 636 patients in the last two groups had an in hospital mortality of 18%, a 30-day mortality 18% and a six month mortality of 25%. In the same group the length of hospital stay was 25.6 days and 68% were discharged to their own home. In conclusion the results of treatment of acute stroke in a medical department with a specialized rehabilitation unit were similar to those reported from acute stroke units in Denmark and abroad, but the patients admitted to our department were younger and fewer were single, which may itself reduce mortality and length of hospital stay.     

Risk factors of persistent or recurrent bleeding and mortality in peptic ulcer hemorrhage

The mortality rate of peptic ulcer haemorrhage has remained unchanged, mainly attributed to rebleeding in an increasingly elderly population with more coexisting systemic diseases. The value of clinical factors and endoscopic findings in predicting in-hospital further haemorrhage and death are analysed. Over a 2-year period, 157 consecutive patients were admitted with bleeding from peptic ulcer, 19 died and 37 had further bleeding. The predictive value of each factor was determined by the chi 2 test with a Yates-correction (significant, p < 0.05). Significant predictive factors of further bleeding were shock, a transfusion requirement > 4 units during the first 48 hours and endoscopic stigmata of recent haemorrhage. The combination of these factors was not of better predictive value than shock alone. The number of coexisting illnesses per patient was strongly related to fatality rate. Other significant factors indicative of an increased mortality included steroid, onset of bleeding during a hospital stay, alcohol, further bleeding, and > 4 units transfused over the first 48 hours. Shock remains the most valuable sign in predicting further bleeding and is superior to endoscopic stigmata. The close relationship between the mortality rate and coexisting illnesses underlines the fact that the majority of deaths result from non peptic ulcer disease.     

Patterns of increased in vivo fundus autofluorescence in the junctional zone of geographic atrophy of the retinal pigment epithelium associated with age-related macular degeneration

BACKGROUND: The impact of upper endoscopy in patients with upper gastrointestinal hemorrhage treated in community practice is unknown. Thus we examined the effectiveness of endoscopy performed within 24 hours of admission (early endoscopy). METHODS: Medical records of 909 consecutive hospitalized patients with upper gastrointestinal hemorrhage who underwent endoscopy at 13 hospitals in a large metropolitan area were reviewed. We evaluated unadjusted and severity-adjusted associations of early endoscopy with recurrent bleeding or surgery to control hemorrhage, length of hospital stay, and associations of endoscopic therapy in patients with bleeding ulcers or varices. RESULTS: Early endoscopy was performed in 64% of patients and compared with delayed endoscopy and was associated with clinically significant reductions in adjusted risk of recurrent bleeding or surgery (odds ratio [OR] 0.70: 95% CI [0.44, 1.13]) and a 31% decrease in adjusted length of stay (95% CI: [24%, 37%]). In patients at high risk for recurrent bleeding, the use of early endoscopic therapy to control hemorrhage was associated with reductions in recurrent bleeding or surgery (OR 0.21: 95% CI [0.10, 0.47]) and length of stay (-31%: 95% CI [-44%, -14%). CONCLUSION: In this study of community-based practice, the routine use of endoscopy, and in selected cases endoscopic therapy, performed early in the clinical course of patients with upper gastrointestinal hemorrhage was associated with reductions in length of stay and, possibly, the risk of recurrent bleeding and surgery.     

Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study

OBJECTIVES: To determine the incidence and case fatality of acute upper gastrointestinal haemorrhage in the west of Scotland and to identify associated factors. DESIGN: Case ascertainment study. SETTING: All hospitals treating adults with acute upper gastrointestinal haemorrhage in the west of Scotland. SUBJECTS: 1882 patients aged 15 years and over treated in hospitals for acute upper gastrointestinal haemorrhage during a six month period. MAIN OUTCOME MEASURES: Incidence of acute upper gastrointestinal haemorrhage per 100,000 population per year, and case fatality. RESULTS: The annual incidence was 172 per 100,000 people aged 15 and over. The annual population mortality was 14.0 per 100,000. Both were higher among elderly people, men, and patients resident in areas of greater social deprivation. Overall case fatality was 8.2%. This was higher among those who bled as inpatients after admission for other reasons (42%) and those admitted as tertiary referrals (16%). Factors associated with increased case fatality were age, uraemia, pre-existing malignancy, hepatic failure, hypotension, cardiac failure, and frank haematemesis or a history of syncope at presentation. Social deprivation, sex, and anaemia were not associated with increased case fatality after adjustment for other factors. CONCLUSIONS: The incidence of acute upper gastrointestinal haemorrhage was 67% greater than the highest previously reported incidence in the United Kingdom, which may be partially attributable to the greater social deprivation in the west of Scotland and may be related to the increased prevalence of Helicobacter pylori. Fatality after acute upper gastrointestinal haemorrhage was associated with age, comorbidity, hypotension, and raised blood urea concentrations on admission. Although deprivation was associated with increased incidence, it was not related to the risk of fatality.     

Complex posttraumatic stress disorder: evidence from the primary care setting

The efficacies of somatostatin and octreotide have been widely studied in the control of bleeding from oesophageal varices. It has also been suggested that these drugs may be useful for the control of non-variceal upper gastrointestinal (UGI) bleeding, including that from peptic ulcers. In approximately 80% of patients presenting with non-variceal UGI bleeding, haemorrhage ceases spontaneously and does not recur. However, the remaining 20% of patients require active treatment. Results from recent studies have indicated that somatostatin is an effective treatment for the control of non-variceal UGI bleeding in high-risk patients, i.e. those in whom haemorrhage does not cease spontaneously or is likely to recur. In contrast there is no good evidence available at present to support a role for octreotide in this indication. The efficacy of somatostatin in controlling bleeding in patients with non-variceal UGI bleeding at high risk of mortality upon admission, or rebleeding following endoscopy, coupled with an excellent safety and tolerability profile, suggests that it may be a valuable therapeutic option in the management of non-variceal bleeding.     

Treatment of acute upper gastrointestinal bleeding: a retrospective study of the results in a surgical clinic

OBJECTIVE: To review our results of the treatment of acute upper gastrointestinal bleeding since 1990. DESIGN: Retrospective study. SETTING: District hospital. SUBJECTS: 226 patients who presented with acute upper gastrointestinal bleeding between January 1990 and April 1992. INTERVENTIONS: Upper gastrointestinal endoscopy and, in 15 cases, emergency laparotomy. MAIN OUTCOME MEASURES: Morbidity and mortality, and the incidence of emergency operations. RESULTS: There were 5 deaths (4%) and 11 emergency operations (10%) in 1990, compared with one death (1%) and 4 operations (4%) during the subsequent 16 months. Duration of hospital stay was reduced from a mean of 7 days to a mean of 6 days and the amount of blood transfused from a mean of 3.4 units to a mean of 2.4 (p < 0.02) over the same period. 149 patients (66%) were over the age of 65 years, 82 (36%) were taking potentially dangerous drugs, and 129 (57%) had serious coexistent diseases. CONCLUSION: We conclude that the natural history of acute upper gastrointestinal bleeding may be changing, and that our "one team" approach comprising immediate resuscitation, urgent endoscopy, emergency operation when indicated, and intensive nursing, is responsible for the improvement in our results over the period of time studied.     

Perioperative TNF alpha and IL-6 concentrations correlate with septic state, organ function, and APACHE II scores in intra-abdominal infection

BACKGROUND: Routine diagnostic endoscopy is commonly obtained for low-risk patients with acute upper gastrointestinal bleeding despite evidence from controlled trials that it does not improve patient outcome. OBJECTIVE: To determine whether endoscopy is being overutilized for these patients or whether considerations not addressed in the trials could justify its widespread use. METHODS: Twenty-five patients recovering from a recent hemorrhage and 22 primary care physicians used the analytic hierarchy process to perform an individualized analysis regarding the diagnostic management of acute upper gastrointestinal bleeding. The results were used to determine whether routine endoscopy was consistent with each subject's interpretation of relevant data and judgments regarding the relative importance of five management goals. The authors then compared the proportion of subjects in each group who preferred endoscopy over two non-endoscopy strategies (upper gastrointestinal series and no routine diagnostic test) with 85%, the current rate of endoscopy at the authors' hospital. RESULTS: Endoscopy was preferred by 92% (97.5% CI: 70%-98%) of the patients and 55% (97.5% CI: 31%-77%) of the physicians. The patients ranked identifying the cause of bleeding the second most important management goal after avoiding a poor outcome from the acute bleeding episode. CONCLUSIONS: The current rate of diagnostic endoscopy is higher than would be expected based on physicians' preferences but quite consistent with patients' preferences. Patients regard knowledge of the bleeding site as important, even if this information will not affect management or prognosis. Attempts to assess the use of diagnostic endoscopy and other diagnostic tests should take both patient preferences and the pure value of diagnostic information into account.     

Hyperplasia and tumor promotion

Ninety-five (24 per cent) of 389 admissions with acute upper gastrointestinal haemorrhage had further haemorrhage. An analysis of factors leading to further haemorrhage was undertaken by considering patients' clinical history, physical state on admission and endoscopic findings. The risk of further haemorrhage was significantly greater in patients bleeding from oesophageal varices or peptic ulcer and in those patients who were sober, shocked or anaemic on admission. Overall, those over 60 years of age were more likely to rebleed, but this difference was not apparent in relation to endoscopic source of blood loss.     

The effectiveness of early endoscopy for upper gastrointestinal hemorrhage: a community-based analysis

OBJECTIVES: The effectiveness of upper endoscopy in unselected patients with upper gastrointestinal hemorrhage has not been well studied. This study was undertaken to identify factors associated with the performance of early endoscopy (ie, within 1 day of hospitalization) and, after adjusting for these factors, to determine associations between early endoscopy and in-hospital mortality, length of stay, and performance of surgery. METHODS: Subjects in this observational cohort study were 3,801 consecutive admissions with upper gastrointestinal hemorrhage to 30 hospitals in a large metropolitan region. Demographic and clinical data were abstracted from hospital records. A multivariable model based on factors that potentially could relate to the decision to perform endoscopy was developed to determine the propensity (0 to 100%) for early endoscopy in each patient. RESULTS: Early endoscopy was performed in 2,240 patients (59%), and although it was not associated with mortality after adjusting for severity of illness among all patients, it was associated with a higher risk of death for patients in the lowest propensity group. Early endoscopy was associated with a lower likelihood of upper gastrointestinal surgery in all patients and in the two highest propensity groups and with a shorter length of stay in the entire cohort and in all subgroups. CONCLUSIONS: In the absence of specific contraindications, early endoscopy should be considered because of associated reductions in length of stay and surgical intervention. Further studies are needed to identify subgroups in whom the procedure may be associated with adverse effects on survival.     

Does HIV status influence the outcome of patients admitted to a surgical intensive care unit? A prospective double blind study

OBJECTIVES: (a) To assess the impact of HIV status (HIV negative, HIV positive, AIDS) on the outcome of patients admitted to intensive care units for diseases unrelated to HIV; (b) to decide whether a positive test result for HIV should be a criterion for excluding patients from intensive care for diseases unrelated to HIV. DESIGN: A prospective double blind study of all admissions over six months. HIV status was determined in all patients by enzyme linked immunosorbent assay (ELISA), immunofluorescence assay, western blotting, and flow cytometry. The ethics committee considered the clinical implications of the study important enough to waive patients' right to informed consent. Staff and patients were blinded to HIV results. On discharge patients could be advised of their HIV status if they wished. SETTING: A 16 bed surgical intensive care unit. SUBJECTS: All 267 men and 135 women admitted to the unit during the study period. INTERVENTIONS: None. MAIN OUTCOME MEASURES: APACHE II score (acute physiological, age, and chronic health evaluation), organ failure, septic shock, durations of intensive care unit and hospital stay, and intensive care unit and hospital mortality. RESULTS: No patient had AIDS. 52 patients were tested positive for HIV and 350 patients were tested negative. The two groups were similar in sex distribution but differed significantly in age, incidence of organ failure (37 (71%) v 171 (49%) patients), and incidence of septic shock (20 (38%) v 54 (15%)). After adjustment for age there were no differences in intensive care unit or hospital mortality or in the durations of stay in the intensive care unit or hospital. CONCLUSIONS: Morbidity was higher in HIV positive patients but there was no difference in mortality. In this patient population a positive HIV test result should not be a criterion for excluding a patient from intensive care.     

Subarachnoid hemorrhage in Vestfold county. Occurrence and prognosis

This prospective study comprises all patients treated for spontaneous non-traumatic subarachnoid haemorrhage between May 1991 and December 1995 in the county of Vestfold, Norway. A total of 76 patients was recorded, giving an incidence of 8.1 per 100 000 per year. Mean age at time of bleeding was 52.7 years. In 36 patients the cause of the bleeding was an intracranial aneurysm; most of the aneurysms were localized to the anterior communicating artery and middle cerebral artery. In seven patients the cause was arteriovenous malformation. 23 patients (30%) died because of their subarachnoid haemorrhage; 15 from the primary bleeding and eight because of re-bleeding. The mortality for patients aged over 60 years was 48%, and for patients younger than 60 years 19%. There was a strict correlation between the initial clinical condition (Hunt & Hess scale) and the final outcome (Glasgow Outcome Scale).     

Emergency fibroendoscopy. Basic exploration in the diagnosis of upper digestive bleeding (experience in 200 cases)

Prognosis in upper gastrointestinal hemorrage (UGIH) depends mostly upon an early diagnosis. The addition of an around the clock endoscopist on duty in the hospital was decided upon to provide inmediate evaluation of all UGIH. The team performed 200 endoscopies, many within the first 12 hours and all of them before 24 hours of bleeding. Endoscopy was unsuccessful in 5 out of 205 attempts. The usefulness of the method was demonstrated as in 94.55% of the patients the cause of the bleeding was established. Peptic ulcers was the cause in 51.5% of the patients and acute inflammatory disease in 14.5%. Esophageal varices were found in 10%, but it is important that we observed 12 patients with non-bleeding varices in which the bleeding was in relation to associated pathologies.     

Mediation of deet repellency in mosquitoes (Diptera: Culicidae) by species, age, and parity

Diabetes insipidus (DI) is an uncommon but important complication in the neurosurgical population. This retrospective study aimed to determine the incidence, profile and outcome of patients admitted to an 18-bedded neurosurgical intensive care unit who developed DI. The overall incidence was 3.7% (29/792 admissions). Aetiologies included subarachnoid haemorrhage (12/29), severe head injury (11/29), post-surgical excision of craniopharyngioma or pituitary adenoma (5/29) and acute haemorrhagic stroke (1/29). All patients were treated with a regime of fluid replacement, electrolyte correction, parenteral or intranasal desmopressin (DDAVP), or parenteral pitressin. Overall mortality was 72.4%. There were no deaths in the patients who underwent excision of tumours. Complications included acute pulmonary oedema, hypernatremia and hypokalaemia. The development of DI was found to be associated with impending brain death and mortality in the majority of patients with subarachnoid haemorrhage and severe head injury. However, careful diagnosis and management of DI after hypothalamo-neurohypophyseal surgery did not result in any permanent neurological sequelae.     

Lions and tigers and bears, oh my!

OBJECTIVE: To examine the use of thrombolytic treatment in acute myocardial infarction when faced with perceived contraindications to treatment and to explore the justification for withholding treatment in such clinical situations. METHODS: Interview survey of all doctors responsible administering thrombolysis to patients with acute myocardial infarction at a teaching hospital in the UK from March to May 1997. RESULTS: 20 doctors were interviewed and asked whether they would give or withhold thrombolysis in a series of 19 clinical situations. These included patients presenting with both an acute myocardial infarction and one of the following associated conditions: a confirmed gastrointestinal haemorrhage, a suspected gastrointestinal haemorrhage, a peptic ulcer, an abdominal aortic aneurysm, a recent cerebrovascular accident, a known intracranial aneurysm, a known intracranial tumour, a recent dental extraction, recent surgery, severe hypertension, proliferative diabetic retinopathy, a history of bleeding diathesis, coma, recent cardiopulmonary resuscitation, pregnancy, menstruation, and a recent central venous puncture. In all but one of the clinical situations (definite current gastrointestinal haemorrhage) there was wide variation in response as to what constitutes a contraindication to thrombolytic treatment. Overall, a substantial proportion of doctors (35%-95%) would withhold treatment on account of any one of these clinical histories. CONCLUSION: Clinicians may be withholding thrombolysis in acute myocardial infarction on account of perceived contraindications for which there is little or no evidence of increased haemorrhagic risk. An effective treatment for acute myocardial infarction is probably being underused.     

Cognitive impairments and mood disturbances in growth hormone deficient men

PURPOSE: Physicians lack objective outcome data to define the medically appropriate length of stay (LOS) for patients hospitalized with acute upper gastrointestinal hemorrhage (UGIH), resulting in wide variations in resource utilization and quality of care. A clinical practice guideline with the ability to assign relative risk for adverse events is proposed. METHODS: A comprehensive scoring system was derived from the literature by using four variables; hemodynamics, time from bleeding, comorbidity, and esophagoduodenoscopy findings. The discriminatory ability, potential safety, and impact on resource utilization of the clinical practice guideline was measured in a retrospective, observational study. RESULTS: Seventy percent of UGIH patients (349 of 500) achieved low-risk status according to the guideline, and, were therefore potentially suitable for early discharge from the hospital. If low-risk patients were discharged based upon the guideline, mean (+/- SD) hospital LOS would have been decreased from 4.8 +/- 2.4 days to 2.7 +/- 1.4 days; mean reduction was 2.1 bed-days per patient (95% CI 1.8 to 2.3, P <0.001). LOS would have increased in 4% of cases. Adopting the guideline's recommendation of early discharge would have resulted in a 0.6% (95% CI 0.07 to 2.1) complication rate, with no worsening of quality of care, as judged by implicit review. CONCLUSIONS: The proposed clinical practice guideline may safely reduce hospital LOS for selected low-risk patients with acute UGIH. Moreover, it also may reduce premature discharge of high-risk patients prone to life-threatening events.     

Definitive emergency treatment of perforated duodenal ulcer

A retrospective survey was made of all patients with a proved diagnosis of perforated duodenal ulcer admitted to a regional hospital during a recent six year period. The over-all mortality from this condition in the 192 patients was 11.4 per cent and mortality after operation, 6.3 per cent. One hundred and seventy-six patients were treated surgically. Seventy-seven patients underwent simple suture only with a mortality of 13 per cent and are compared with 99 patients treated by emergency vagotomy and pyloroplasty procedures with a 1 per cent mortality. Emergency definitive operations were performed without increased morbidity, mortality or hospital stay by junior surgeons with greatly improved long term results compared with simple suture. At the present time, emergency vagotomy and pyloroplasty procedures are the treatment of choice for a perforated duodenal ulcer.     

Safety, efficacy, and cost of pancreaticoduodenal resection in a specialized center based at a community hospital

OBJECTIVE: To determine whether pancreaticoduodenal resection (PDR) for benign and malignant disease can be performed safely, efficiently, and economically at a 50-bed community hospital. DESIGN: Retrospective review of 39 consecutive PDRs performed in an 18-month period. Indications for surgery, length of hospital stay, complications, and patient charges were analyzed. SETTING: A suburban 50-bed community hospital. PATIENTS: Thirty-nine patients (15 male and 24 female) referred for PDR for benign and malignant disease. MAIN OUTCOME MEASURES: Mortality and morbidity rates, length of hospital stay, care, and cost. RESULTS: Of 39 patients who underwent PDRs, 1 patient (2.6%) died of myocardial infarct. Intraoperative blood transfusions were required by 3 patients (8%). The mean postoperative hospital stay was 11 days. Twenty-four patients (62%) were discharged by day 11. Fifteen patients (38%) were hospitalized 11 to 24 days. Complications in 10 patients (28%) included pancreatic or biliary fistula (n = 6), upper gastrointestinal tract bleeding (n = 1), partial wound dehiscence (n = 1), bacteremia (n = 1), and pneumonia (n = 1). No patient required reoperation. Three patients were rehospitalized within 1 month. Mean patient charges were $21,864, and mean reimbursements were $19,669. CONCLUSIONS: Pancreaticoduodenal resection can be accomplished with low morbidity and mortality rates and a short stay at a community hospital. Thorough preoperative investigations to exclude unresectable lesions must precede every PDR for malignant disease. Mortality and morbidity rates in this series were similar to those for patients with similar diagnoses who were operated on in academic centers. Cost for and length of hospital stay of these 39 patients were significantly lower than those in other reported series.     

Outreach education to improve quality of rural ICU care. Results of a randomized trial

This study tests whether an outreach educational program tailored to institutional specific patient care practices would improve the quality of care delivered to mechanically ventilated intensive care unit (ICU) patients in rural hospitals. The study was conducted as a randomized control trial using 20 rural Iowa hospitals as the unit of analysis. Twelve randomly selected hospitals received an outreach educational program. After review of the medical records of eligible patients, a multidisciplinary team of intensive care unit specialists from an academic medical center delivered an educational program with content specific to the findings and capacity of the hospital. The outcome measures included patient care processes, patient morbidity and mortality outcomes, and resource use. Results indicated that the outreach program significantly improved many patient care processes (lab work, nursing, dietary management, ventilator management, ventilator weaning). The program marginally reduced hospital ventilator days. Both total length of stay and ICU length of stay fell markedly in the intervention group (by an average of 3.2 and 2.1 d, respectively), while the control group fell only 0.6 and 0.3 d, respectively. However, these effects did not reach statistical significance. Unfortunately, the program had no detectable effects on the clinical outcomes of mortality or nosocomial events. We conclude that an outreach program of this type can effectively improve processes of care in rural ICUs. However, improving processes of care may not always translate into improvement of specific outcomes.     

Treatment costs in a medical intensive care unit: a comparison of 1992 and 1997

BACKGROUND AND OBJECTIVE: Treatment in an intensive care unit (ICU) is very expensive. Aim of this study was to determine the exact composition of costs and to analyse what factors are responsible for the rise in costs over the last 5 years. METHODS: In a prospective investigation all 790 patients who had been treated at the ICU of the Medical Department of Frankfurt University during 1992 were included, findings being compared with data on all 208 patients treated in the ICU in May and June 1997. All important diagnostic and therapeutic measures were quantitatively determined each day. RESULTS: The mean age of the ICU patients rose in the 5 years from 55 to 59 years (P < 0.001). Mean period of stay in the ICU remained unchanged (4.1 days), total duration of hospital stay (15 and 12 days, respectively), and treatment intensity (sum of points according to the "Therapeutic Intervention Scoring System" per ICU stay: 96 and 77, respectively). The mortality rate in the ICU fell from 16.3% to 10.6% (P = 0.02), hospital mortality rate from 23% to 14% (P = 0.01). Total cost rose from DM 797,860 to DM 1,148,945 per 100 patients (+44%). Of this total, personnel costs were DM 286,885 in 1992 and 356,091 in 1997 (+24%), costs for apparatus-based diagnostic and therapeutic tests were DM 169,743 and 245,156, respectively (+44%), DM 98,496 and 129,222 for drugs (+31%), and DM 60,399 and 186,671 (+209%) for blood and clotting products (in each category per 100 patients). Per case costs rose from DM 7970 to 11,489, per day costs from DM 1943 to 2831. 90% of cost increases were due to new strategies in the treatment of patients with myocardial infractions and those with severe clotting disorders and a rise in personnel costs. CONCLUSION: The costs of a stay in the ICU has greatly increased over the last 5 years, the main causes being a change to new forms of treatment, especially in patients with myocardial infarction and those with haemophilia.