Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication.

BACKGROUND: Intermittent claudication is a disabling symptom of peripheral arterial disease for which few medical treatments are available. This study investigated the effect of caffeine on physical capacity in patients with intermittent claudication. METHODS: This randomized double-blind placebo-controlled crossover study included 88 patients recruited by surgeons from outpatient clinics. The participants abstained from caffeine for 48 h before each test and then received either a placebo or oral caffeine (6 mg/kg). After 75 min, pain-free and maximal walking distance on a treadmill, perceived pain, reaction times, postural stability, maximal isometric knee extension strength, submaximal knee extension endurance and cognitive function were measured. The analysis was by intention to treat. RESULTS: Caffeine increased the pain-free walking distance by 20.0 (95 per cent confidence interval 3.7 to 38.8) per cent (P = 0.014), maximal walking distance by 26.6 (12.1 to 43.0) per cent (P < 0.001), muscle strength by 9.8 (3.0 to 17.0) per cent (P = 0.005) and endurance by 21.4 (1.2 to 45.7) per cent (P = 0.004). However, postural stability was reduced significantly, by 22.1 (11.7 to 33.4) per cent with eyes open (P < 0.001) and by 21.8 (7.6 to 37.8) per cent with eyes closed (P = 0.002). Neither reaction time nor cognition was affected. CONCLUSION: In patients with moderate intermittent claudication, caffeine increased walking distance, maximal strength and endurance, but affected balance adversely.

Drug therapy for improving walking distance in intermittent claudication: a systematic review and meta-analysis of robust randomised controlled studies.

OBJECTIVES: To evaluate the efficacy of pharmacological interventions in improving walking capacity and health-related quality of life for people with intermittent claudication. DATASOURCES: We searched Medline, EMBASE, Cochrane library and relevant websites for studies published from the start of the databases to February 2009. In addition, reference lists were manually searched. REVIEW METHODS: Based upon a power calculation, only robust (n>56), peer-reviewed, double-blinded, randomised and placebo-controlled trials were included. The main outcomes evaluated were maximal walking distance (MWD) and pain-free walking distance on a treadmill. Random models were used in the statistical analysis, and chi-square test were used to test for heterogeneity. RESULTS: Among 220 trials, only 43 trials fulfilled the quality criteria. Treatment periods, follow-up and treadmill protocols varied substantially. Vasodilator agents and phosphodiesterase inhibitors show robust significant results compared to placebo, but the improvements in MWD are modest. The highest benefit was caused by lipid-lowering agents, which in mean gained above 160 m in MWD, while the other agents only improved MWD about 50 m. CONCLUSION: Several drugs have shown to improve MWD, but with limited benefits. Statins seem to be the most efficient drug at the moment.

Nationwide population-based cohort study to assess risk of surgery for adhesive small bowel obstruction following open or laparoscopic rectal cancer resection.

BACKGROUND: Laparoscopic surgery has been reported to reduce the formation of adhesions following colorectal surgery. The aim of this nationwide cohort study was to investigate the risk of surgery for adhesive small bowel obstruction (SBO) following open and laparoscopic rectal cancer resection. METHODS: Patients undergoing rectal cancer resection between 2005 and 2013 were identified in the Danish Colorectal Cancer Group database. The primary outcome of surgery for adhesive SBO was identified in the Danish National Patient Registry. The risk of surgery for adhesive SBO was estimated as the cumulative incidence proportion, treating death as a competing risk. Cox proportional hazards regression analysis with multivariable adjustment was used to compute hazard ratios (HRs). The secondary outcome was 30-day mortality after surgery for adhesive SBO. RESULTS: Of 7657 patients, 340 (4·4 per cent) underwent surgery for adhesive SBO. The 5-year risk of surgery for adhesive SBO was 4·5 per cent among 4472 patients undergoing open resection and 3·0 per cent among 3185 patients having a laparoscopic resection. Laparoscopic rectal resection was associated with a lower risk of subsequent operation for adhesive SBO (adjusted HR 0·65, 95 per cent c.i. 0·50 to 0·86; P = 0·002). The adjusted HR of mortality after adhesive SBO was 0·84 (0·37 to 1·91; P = 0·671) comparing patients with previous laparoscopic and open resection. CONCLUSION: Laparoscopic rectal cancer resection was associated with a decreased risk of surgery for adhesive SBO. There was a substantial difference in 30-day mortality after surgery for adhesive SBO based on the surgical approach used at the time of rectal resection.

Effect of darbepoetin alfa on physical function in patients undergoing surgery for colorectal cancer. A randomized, double-blind, placebo-controlled study.

OBJECTIVE: To study whether perioperative treatment with darbepoetin alfa (DA) improves physical performance following colorectal cancer surgery. METHODS: Patients admitted for planned colorectal cancer surgery were randomized to receive either weekly placebo or DA 300 or 150 microg depending on the hemoglobin (Hb) concentration. Patients were assessed 10 days before, as well as 7 and 30 days after surgery for work capacity, postural sway, muscle strength, fatigue and quality of life (QoL). The primary outcome measure were the changes in patients' physical performance from preoperative to postoperative day 7. RESULTS: Of 221 included patients, 151 were evaluable. Baseline characteristics were similar in the 2 groups. Patients receiving DA had a significantly better working capacity on day 7 (p = 0.03) and day 30 (p = 0.03) compared with the placebo group. There were no statistically significant differences between the 2 groups on days 7 or 30 for fatigue, postural sway and QoL. DA treatment significantly (p < 0.01) reduced the decrease in Hb concentrations on day 7 and resulted in an earlier return (p < 0.01) to the preoperative Hb concentration compared to placebo treatment. CONCLUSION: Perioperative DA treatment improved postoperative work capacity and Hb concentrations, but had no effect on postoperative fatigue, postural sway, QoL and muscle strength.

Caffeine improves endurance in 75-yr-old citizens: a randomized, double-blind, placebo-controlled, crossover study.

This study investigated the effect of caffeine on physical performance in healthy citizens aged > or =70 yr. The randomized, double-blind, placebo-controlled, crossover study was conducted in 15 men and 15 women recruited by their general practitioner. Participants abstained from caffeine for 48 h and were randomized to receive one capsule of placebo and then caffeine (6 mg/kg) or caffeine and then placebo with 1 wk in between. One hour after intervention, we measured reaction and movement times, postural stability, walking speed, cycling at 65% of expected maximal heart rate, perceived effort during cycling, maximal isometric arm flexion strength, and endurance. Analysis was by intention to treat, and P < 0.05 was regarded as significant. Caffeine increased cycling endurance by 25% [95% confidence interval (CI): 13-38; P = 0.0001] and isometric arm flexion endurance by 54% (95% CI: 29-83; P = 0.0001). Caffeine also reduced the rating of perceived exertion after 5 min of cycling by 11% (95% CI: 5-17; P = 0.002) and postural stability with eyes open by 25% (95% CI: 2-53; P = 0.03). Caffeine ingestion did not affect muscle strength, walking speed, reaction, and movement times. At the end of the study, 46% of participants correctly identified when they received caffeine and placebo. Caffeine increased exercise endurance in healthy citizens aged > or =70 yr, but the participants' reasons for stopping the test may have varied between subjects, as the cycling test was done at approximately 55% of maximal oxygen consumption. Further studies are required to investigate whether caffeine can be utilized to improve the physical performance of elderly citizens.

[Laparatomy in patients aged 80 years and older. A prospective analysis of morbidity during 1 year in the county of Ringkøbing]. / Laparotomi på patienter over 80 år gamle. En prospektiv analyse of morbiditet og mortalitet gennem et år i Ringkøbing Amt.

All patients aged 80 years or more admitted to the departments of general surgery in Ringkøbing county, Denmark, during one year were studied prospectively in order to investigate morbidity and mortality following laparotomy in this patient group. A laparotomy was performed in 94 patients (67% women), in 73% as emergency cases. More than half of the patients had important coexisting diseases, and in half of the patients the cause of laparotomy was malignant disease, mostly colorectal cancer, while perforated or bleeding ulcer, cholecystitis, appendicitis, diverticulitis and incarcerated hernias were the most common benign causes of laparotomy. Postoperative complications were seen in 43% of the patients with a total mortality rate of 22%, mostly due to cardiac problems. Coexisting disease and emergency operation significantly increased both morbidity and mortality, which varied from respectively 8% and 0% after elective laparotomy in patients without coexisting diseases to respectively 71% and 39% after emergency operations in patients with coexisting diseases. In conclusion, laparotomy carries a high risk in elderly patients, particularly in the emergency situation. Efforts must be made in these patients to correct and treat any coexisting medical disorder prior to surgery, and when possible to perform early surgery before an elective operation turns into an emergency problem. Also, the development of new surgical procedures with lower morbidity must be encouraged.

[Parenchymal surgery in patients aged 80 and over--a coming crisis? An analysis of current status and results and an attempt to illuminate future needs]. / Parenkymkirurgi på patienter over 80 år--kommende krise? En analyse of nuvaerende aktivitet og resultater og et forsøg på at belyse fremtidigt behov.

This study reviews 594 admissions of 434 patients aged 80 years or more to the departments of general surgery in Ringkobing County, Denmark, during one year. Half of the patients were admitted as emergencies, and 60% underwent surgery. The overall mortality was 9%, the postoperative mortality 8%. The number of postoperative complications and the postoperative mortality rate increased in emergency cases and in patients with complicating medical diseases. 72% of all admissions were uncomplicated and 69% of the patients were discharged directly home. Generally, these patients do not block beds, but are discharged as soon as medical care is no longer indicated. During this decade it is expected that the number of admissions of patients aged 80 years or older will increase by about 25%, and unless additional resources are provided, new standards must be considered for the distribution of resources and of indications for surgery in both young and old. Also, the development of less traumatic methods of operative surgery with lower morbidity rates, earlier recovery and reduced hospital stay must be encouraged.

[Surgical treatment of goiter at a central hospital. A consecutive adjustment after changes in the organization, strategy and surgical techniques]. / Kirurgisk behandling af struma på et centralsygehus. En konsekutiv opgørelse efter aendringer i organisation, strategi og kirurgisk teknik.

The aim of the study was to analyze the frequency of complications following thyroid gland surgery in a surgical department of a district hospital. Since the results of the department were last evaluated in 1988, changes in surgical strategy and operative techniques have been introduced. Hemithyroidectomy with resection of the glandular isthmus is now the least comprehensive operation performed, and at all operations the recurrent laryngeal nerve is identified and exposed. One hundred and twenty-five operations were carried out over a five years period. Half of the patients were operated for non-toxic nodular goitre, and 24 patients for thyrotoxicosis. Of 23 patients with a scintigraphically "cold" nodule, four turned out to have carcinoma. The frequency of permanent complications were 0.8% (hypoparathyroidism in one patient). Transient hypoparathyroidism was seen in 2%, and in four patients (3%) transient unilateral nerve palsy developed. No cases of permanent or bilateral vocal cord paralysis were found. Remaining complications were haemorrhage (2%) and one patient with a complication not related to surgery (0.8%). The departments results have improved significantly since 1988, and it is concluded that uncomplicated thyroid gland surgery may safely be performed at a district hospital.

[Pre-therapeutic assessment of resectability in patients with upper gastrointestinal cancer. Combined use of endoscopic ultrasonography and laparoscopy]. / Praeterapeutisk resektabilitetsvurdering af patienter med øvre gastrointestinal cancer. Kombination af endoskopisk ultralydskanning og laparoskopi.

The combined use of endoscopic ultrasonography (EUS) and laparoscopy for the assessment of resectability in patients with upper GI tract cancer was prospectively evaluated in 57 patients. Laparoscopy was able to fill the informational gap in all the patients (n = 6) where EUS failed to give a complete assessment of resectability. This study suggests that the combination of EUS and laparoscopy can reduce the need for "necessary" laparoscopies to about 10%.

[Preoperative laparoscopic evaluation of patients with upper gastrointestinal cancer]. / Laparoskopisk operabilitetsvurdering af patienter med øvre gastrointestinal cancer.

Nineteen consecutive patients with adenocarcinoma of the stomach or pancreas, in whom preoperative ultrasonography and computed tomography were unable to assess the possibility of surgical resection, had a diagnostic laparoscopy performed. In 16 cases the operability could be established from the findings at laparoscopy. All laparoscopies were carried out without major morbidity and with a short postoperative hospital stay. It is concluded that patients belonging to this category should have a diagnostic laparoscopy performed in order to avoid futile laparotomies, which in cases that are unsuitable for surgical treatment are associated with emotional stress, physical morbidity and a prolonged hospital stay.

[Non-surgical treatment of bleeding gastric ulcer. A follow-up after 5-8 years]. / Ikkeoperativ behandling af blødende ulcus ventriculi. Opfølgning efter 5-8 år.

UNLABELLED: Gastric ulcer haemorrhage is associated with a high immediate mortality, but few data exist on the late prognosis of these patients. The aim of this study was to determine the long-term recurrence rate and late outcome in patients with gastric ulcer complicated by bleeding. In a prospective follow-up study 90 consecutive patients with a bleeding gastric ulcer discharged after non-operative treatment (bleeding controlled by endoscopic electrocoagulation or ceased spontaneously) were followed up once every year for five to eight years (median 6.5 years). Recurrent ulcer was seen in 17 patients, repeat haemorrhage being the presenting symptom in 13. The estimated cumulative recurrence rate after two, five and eight years was 10%, 19% and 33%, respectively. Recurrence rate was unaffected by sex, complicating disease, and NSAID ingestion before and after the index bleeding episode. The recurrence rate of patients with a history of ulcer before the index bleeding episode did not differ from that of patients with no previous ulcer history. A significantly increased risk of recurrence was seen in patients with previous bleed as opposed to patients with previous non-bleeding ulcer (p < 0.05). The cumulative survival rate was significantly reduced compared to the expected survival rate of the sex- and age-matched background population (p < 0.01), primarily due to diseases not related to the ulcer disease. CONCLUSION: Bleeding gastric ulcer is associated with a relatively low long-term recurrence rate, except in a few patients with a history of previous bleeding ulcer, who have an increased risk of recurrence. Patients with bleeding gastric ulcer have an excess mortality not related to the ulcer disease.

[Laparoscopic ultrasonography. A review and authors' own experiences]. / Laparoskopisk ultralydskanning. Oversigt og egne erfaringer.

Laparoscopic ultrasound scanning has long been available, but interest in and reports of the technique have until the last few years been sporadic. The rapid development and growing interest in laparoscopic surgery as well as the advent of commercially available systems designed for laparoscopic ultrasound have resulted in renewed interest in the technique. The available published reports lack prospective, controlled clinical studies with respect to where and when laparoscopic ultrasound would be indicated. A favourable picture is given as concerns the use of laparoscopic ultrasound in the diagnosis and evaluation of primary liver and pancreas tumours as well as liver metastases. Laparoscopic ultrasound is also mentioned as a reliable alternative to cholangiography in laparoscopic cholecystectomy. Our own preliminary experiences with two laparoscopic ultrasound systems and a simple system using an ultrasound finger-probe are described. A laparoscopic ultrasound scanning system consisting of a stiff instrument with a convex (linear) transducer mounted on a flexible support and with the possibility of ultrasound-guided biopsy and colour-Doppler seems optimal. Prospective studies are being carried out to identify areas of utilization and limitations of laparoscopic ultrasound.

[Anastomotic leakage after low anterior resection for rectal cancer]. / Anastomoselaekage efter lav anterior resektion for cancer recti.

A series of 377 consecutive patients were operated upon with low anterior resection for rectal cancer in the nine Danish departments of surgical gastroenterology during 1992-1993. A retrospective analysis was carried out to calculate the frequency of anastomotic leakage and to evaluate factors of potential influence on the development of leakage according to the literature. Sixty-three patients (17%) developed leakage, which was followed by an increased mortality within the first three postoperative months. Only two variables significantly influenced the leakage rate: male gender was associated with a higher leakage rate (p = 0.02), whereas departments with a low number of rectal cancer surgeons had a low rate of anastomotic leakage (p = 0.02). In conclusion, the rather high frequency of anastomotic leakage calls for further clinical and pathogenetic research in this field. Until then, we recommend the routine use of a peroperative leakage test and selective use of prophylactic ostomy in cases of unsatisfactory anastomosis. Furthermore, it is recommended that low anterior resection for rectal cancer is limited to few surgeons in each department in order to ensure a uniform quality and hopefully also thereby reduce the rate of anastomotic leakage.

Trends in colorectal cancer survival in northern Denmark: 1985-2004.

OBJECTIVE: The prognosis for colorectal cancer (CRC) is less favourable in Denmark than in neighbouring countries. To improve cancer treatment in Denmark, a National Cancer Plan was proposed in 2000. We conducted this population-based study to monitor recent trends in CRC survival and mortality in four Danish counties. METHOD: We used hospital discharge registry data for the period January 1985-March 2004 in the counties of north Jutland, Ringkjøbing, Viborg and Aarhus. We computed crude survival and used Cox proportional hazards regression analysis to compare mortality over time, adjusted for age and gender. A total of 19,515 CRC patients were identified and linked with the Central Office of Civil Registration to ascertain survival through January 2005. RESULTS: From 1985 to 2004, 1-year and 5-year survival improved both for patients with colon and rectal cancer. From 1995-1999 to 2000-2004, overall 1-year survival of 65% for colon cancer did not improve, and some age groups experienced a decreasing 1-year survival probability. For rectal cancer, overall 1-year survival increased from 71% in 1995-1999 to 74% in 2000-2004. Using 1985-1989 as reference period, 30-day mortality did not decrease after implementation of the National Cancer Plan in 2000, neither for patients with colon nor rectal cancer. However, 1-year mortality for patients with rectal cancer did decline after its implementation. CONCLUSION: Survival and mortality from colon and rectal cancer improved before the National Cancer Plan was proposed; after its implementation, however, improvement has been observed for rectal cancer only.

Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study.

OBJECTIVE: Whereas caffeine has been demonstrated to impact substantially on the metabolic response to exercise in healthy young subjects, this issue remains to be addressed in healthy elderly subjects. DESIGN AND PATIENTS: The metabolic response to caffeine ingestion (6 mg/kg) and exercise in healthy elderly citizens at 70 years was examined in a randomized, double-blind, placebo-controlled, cross-over study. We included 30 subjects attending for driver license renewal at their general practitioner. Participants abstained from caffeinated drinks and food for 48 h and were randomized to receive placebo-caffeine or caffeine-placebo with 1 week between sessions. MEASUREMENTS: A cycling endurance test at 65% of the expected maximal heart rate was performed 1 h after intervention. Blood samples were taken before intervention, before cycling, after 5 min of cycling, and at exhaustion. Analysis was by intention-to-treat and P < 0.05 was regarded as significant. RESULTS: Caffeine significantly increased the concentration of plasma epinephrine (by 42%, 39%, and 49%), serum-free fatty acids (by 53%, 44%, and 50%), and plasma lactate (by 46%, 36%, and 48%), and insulin resistance (homeostasis model assessment-IR) (by 21%, 26%, and 23%) during rest, after 5 min of cycling, and at exhaustion. At exhaustion, the concentration plasma norepinephrine was elevated by 29%. A decrease was seen with caffeine treatment in blood potassium after 5 min of cycling and at exhaustion (by 3% and 2%, respectively). CONCLUSIONS: Caffeine treatment increased epinephrine, fatty acids, lactate and norepinephrine at different times during test session and led to insulin-resistance. Hence, caffeine ingestion elicits a similar metabolic response in elderly participants at 70 years old to that seen in younger subjects.