Linköping University Hospital

Many different methods of evaluating disability after knee ligament injury exist. Most of them differ in design. Some are based on only patients' symptoms. Other include patients' symptoms, activity grading, performance in a test, and clinical findings. The rating in these evaluating systems can be either numerical, as in a score, or binary, with yes/no answers. Comparison between a symptom-related score and a score of more complex design showed that the symptom-related score gave a more differentiated picture of the disability. It was also shown that the binary rating system gave less detailed information than a score and that differences in a binary rating can depend on at what level the symptoms are regarded as "significant." A new activity grading scale, where work and sport activities were graded numerically, was constructed as complement to the functional score. When evaluating knee ligament injuries, stability testing, functional knee score, performance test, and activity grading are all important. However, the relative importance varies during the course of treatment, and therefore they should not all be included in one and the same score.

We have designed a scoring scale for knee ligament surgery follow-up emphasizing evaluation of symptoms of instability. Instability is defined as "giving way" during activity. Our scoring scale was compared to a slightly modified Larson scale in patients with anteromedial and/or anterolateral instability, posterolateral and straight posterior instability, chondromalacia patellae, and meniscus lesion. The two scales gave basically the same results in patients with meniscus rupture. In patients with unstable knees, the new scale gave a significantly lower total score. Thus, the new scale evaluates functional impairment due to clinical instability better than the modified Larson scale. The total score, with the new scoring scale, corresponded to the patients' own opinion of function and to the presence or absence of signs of instability.

BACKGROUND: Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS: In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS: Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS: Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).

BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. METHODS: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. RESULTS: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). CONCLUSIONS: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).

Available standard intrauterine growth curves based on birthweights underestimate foetal growth in preterm period. New growth curves are presented based on data from four Scandinavian centres for 759 ultrasonically estimated foetal weights in 86 uncomplicated pregnancies. Mean weight of boys exceeded that of girls by 2-3%. A uniform SD value of 12% of the mean weight was adopted for the standard curves as the true SD varied non-systematically between 9.1 and 12.4%. Applied to an unselected population of 8663 singleton births, before 210 days of gestation, 32% of birthweights were classified as small-for-gestational age (SGA; i.e. below mean - 2 SD); the corresponding figures were 11.1% for gestational ages between 210 and 258 days, and 2.6% for ages of 259 days or longer. The new growth curves reveal better the true distribution of SGA foetuses and neonates, and are suggested for use in perinatological practice.

OBJECTIVE: To assess in diabetic patients with coronary heart disease (CHD) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events. RESEARCH DESIGN AND METHODS: A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infarction or angina pectoris, serum total cholesterol 5.5-8.0 mmol/l, and serum triglycerides < or = 2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S). Participants in the 4S were randomly assigned to double-blind treatment with simvastatin, 20 mg daily, with blinded dosage titration up to 40 mg daily, according to cholesterol response during the first 6-18 weeks, or placebo. Endpoints were 1) total mortality, 2) major CHD events (CHD death or nonfatal myocardial infarction), 3) other acute atherosclerotic events, 4) myocardial revascularization procedures. RESULTS: Over the 5.4-year median follow-up period, simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients. The relative risks (RRs) of main endpoints in simvastatin-treated diabetic patients were as follows: total mortality 0.57 (95% CI, 0.30-1.08; P = 0.087), major CHD events 0.45 (95% CI, 0.27-0.74; P = 0.002), and any atherosclerotic event 0.63 (95% CI, 0.43-0.92; P = 0.018). The corresponding RRs in nondiabetic patients were the following: 0.71 (95% CI, 0.58-0.87; P = 0.001), 0.68 (95% CI, 0.60-0.77; P < 0.0001), and 0.74 (95% CI, 0.68-0.82; P < 0.0001). CONCLUSIONS: The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD. The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events.

Cardiovascular disease (CVD) and depression are common. Patients with CVD have more depression than the general population. Persons with depression are more likely to eventually develop CVD and also have a higher mortality rate than the general population. Patients with CVD, who are also depressed, have a worse outcome than those patients who are not depressed. There is a graded relationship: the more severe the depression, the higher the subsequent risk of mortality and other cardiovascular events. It is possible that depression is only a marker for more severe CVD which so far cannot be detected using our currently available investigations. However, given the increased prevalence of depression in patients with CVD, a causal relationship with either CVD causing more depression or depression causing more CVD and a worse prognosis for CVD is probable. There are many possible pathogenetic mechanisms that have been described, which are plausible and that might well be important. However, whether or not there is a causal relationship, depression is the main driver of quality of life and requires prevention, detection, and management in its own right. Depression after an acute cardiac event is commonly an adjustment disorder than can improve spontaneously with comprehensive cardiac management. Additional management strategies for depressed cardiac patients include cardiac rehabilitation and exercise programmes, general support, cognitive behavioural therapy, antidepressant medication, combined approaches, and probably disease management programmes.

BACKGROUND: Recent reports have indicated that there may be an increased risk of late stent thrombosis with the use of drug-eluting stents, as compared with bare-metal stents. METHODS: We evaluated 6033 patients treated with drug-eluting stents and 13,738 patients treated with bare-metal stents in 2003 and 2004, using data from the Swedish Coronary Angiography and Angioplasty Registry. The outcome analysis covering a period of up to 3 years was based on 1424 deaths and 2463 myocardial infarctions and was adjusted for differences in baseline characteristics. RESULTS: The two study groups did not differ significantly in the composite of death and myocardial infarction during 3 years of follow-up. At 6 months, there was a trend toward a lower unadjusted event rate in patients with drug-eluting stents than in those with bare-metal stents, with 13.4 fewer such events per 1000 patients. However, after 6 months, patients with drug-eluting stents had a significantly higher event rate, with 12.7 more events per 1000 patients per year (adjusted relative risk, 1.20; 95% confidence interval [CI], 1.05 to 1.37). At 3 years, mortality was significantly higher in patients with drug-eluting stents (adjusted relative risk, 1.18; 95% CI, 1.04 to 1.35), and from 6 months to 3 years, the adjusted relative risk for death in this group was 1.32 (95% CI, 1.11 to 1.57). CONCLUSIONS: Drug-eluting stents were associated with an increased rate of death, as compared with bare-metal stents. This trend appeared after 6 months, when the risk of death was 0.5 percentage point higher and a composite of death or myocardial infarction was 0.5 to 1.0 percentage point higher per year. The long-term safety of drug-eluting stents needs to be ascertained in large, randomized trials.

BACKGROUND: The use of iodinated contrast medium can result in nephropathy. Whether iso-osmolar contrast medium is less nephrotoxic than low-osmolar contrast medium in high-risk patients is uncertain. METHODS: We conducted a randomized, double-blind, prospective, multicenter study comparing the nephrotoxic effects of an iso-osmolar, dimeric, nonionic contrast medium, iodixanol, with those of a low-osmolar, nonionic, monomeric contrast medium, iohexol. The study involved 129 patients with diabetes with serum creatinine concentrations of 1.5 to 3.5 mg per deciliter who underwent coronary or aortofemoral angiography. The primary end point was the peak increase from base line in the creatinine concentration during the three days after angiography. Other end points were an increase in the creatinine concentration of 0.5 mg per deciliter or more, an increase of 1.0 mg per deciliter or more, and a change in the creatinine concentration from day 0 to day 7. RESULTS: The creatinine concentration increased significantly less in patients who received iodixanol. From day 0 to day 3, the mean peak increase in creatinine was 0.13 mg per deciliter in the iodixanol group and 0.55 mg per deciliter in the iohexol group (P=0.001; the increase with iodixanol minus the increase with iohexol, -0.42 mg per deciliter [95 percent confidence interval, -0.73 to -0.22]). Two of the 64 patients in the iodixanol group (3 percent) had an increase in the creatinine concentration of 0.5 mg per deciliter or more, as compared with 17 of the 65 patients in the iohexol group (26 percent) (P=0.002; odds ratio for such an increase in the iodixanol group, 0.09 [95 percent confidence interval, 0.02 to 0.41]). No patient receiving iodixanol had an increase of 1.0 mg per deciliter or more, but 10 patients in the iohexol group (15 percent) did. The mean change in the creatinine concentration from day 0 to day 7 was 0.07 mg per deciliter in the iodixanol group and 0.24 mg per deciliter in the iohexol group (P=0.003; value in the iodixanol group minus the value in the iohexol group, -0.17 mg per deciliter [95 percent confidence interval, -0.34 to -0.07]). CONCLUSIONS: Nephropathy induced by contrast medium may be less likely to develop in high-risk patients when iodixanol is used rather than a low-osmolar, nonionic contrast medium.

In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results.

Acute myeloid leukemia (AML) is most common in the elderly, and most elderly are thought to be unfit for intensive treatment because of the risk of fatal toxicity. The Swedish Acute Leukemia Registry covers 98% of all patients with AML (nonacute promyelocytic leukemia) diagnosed in 1997 to 2005 (n = 2767), with a median follow-up of 5 years, and reports eligibility for intensive therapy, performance status (PS), complete remission rates, and survival. Outcomes were strongly age and PS dependent. Early death rates were always lower with intensive therapy than with palliation only. Long-term survivors were found among elderly given intensive treatment despite poor initial PS. Total survival of elderly AML patients was better in the geographic regions where most of them were given standard intensive therapy. This analysis provides unique real world data from a large, complete, and unselected AML population, both treated and untreated, and gives background to treatment decisions for the elderly. Standard intensive treatment improves early death rates and long-term survival compared with palliation. Most AML patients up to 80 years of age should be considered fit for intensive therapy, and new therapies must be compared with standard induction.

BACKGROUND: Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. METHODS: Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. RESULTS: During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). CONCLUSIONS: Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.).

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).

BACKGROUND: Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes. METHODS: In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes. RESULTS: After five years, the change in the glomerular filtration rate was -17.5 ml per minute per 1.73 m2 (where the minus sign denotes a decrement) in the telmisartan-treated subjects, as compared with -15.0 ml per minute per 1.73 m2 in the enalapril-treated subjects; the treatment difference was thus -2.6 ml per minute per 1.73 m2 (95 percent confidence interval, -7.1 to 2.0 ml per minute per 1.73 m2)[corrected] The lower boundary of the confidence interval, in favor of enalapril, was greater than the predefined margin of -10.0 ml per minute per 1.73 m2, indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years. CONCLUSIONS: Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events.

Deciding when to return to sport after injury is complex and multifactorial-an exercise in risk management. Return to sport decisions are made every day by clinicians, athletes and coaches, ideally in a collaborative way. The purpose of this consensus statement was to present and synthesise current evidence to make recommendations for return to sport decision-making, clinical practice and future research directions related to returning athletes to sport. A half day meeting was held in Bern, Switzerland, after the First World Congress in Sports Physical Therapy. 17 expert clinicians participated. 4 main sections were initially agreed upon, then participants elected to join 1 of the 4 groups-each group focused on 1 section of the consensus statement. Participants in each group discussed and summarised the key issues for their section before the 17-member group met again for discussion to reach consensus on the content of the 4 sections. Return to sport is not a decision taken in isolation at the end of the recovery and rehabilitation process. Instead, return to sport should be viewed as a continuum, paralleled with recovery and rehabilitation. Biopsychosocial models may help the clinician make sense of individual factors that may influence the athlete's return to sport, and the Strategic Assessment of Risk and Risk Tolerance framework may help decision-makers synthesise information to make an optimal return to sport decision. Research evidence to support return to sport decisions in clinical practice is scarce. Future research should focus on a standardised approach to defining, measuring and reporting return to sport outcomes, and identifying valuable prognostic factors for returning to sport.

Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians: 1) NP levels are quantitative plasma biomarkers of heart failure (HF). 2) NP levels are accurate in the diagnosis of HF. 3) NP levels may help risk stratify emergency department (ED) patients with regard to the need for hospital admission or direct ED discharge. 4) NP levels help improve patient management and reduce total treatment costs in patients with acute dyspnoea. 5) NP levels at the time of admission are powerful predictors of outcome in predicting death and re-hospitalisation in HF patients. 6) NP levels at discharge aid in risk stratification of the HF patient. 7) NP-guided therapy may improve morbidity and/or mortality in chronic HF. 8) The combination of NP levels together with symptoms, signs and weight gain assists in the assessment of clinical decompensation in HF. 9) NP levels can accelerate accurate diagnosis of heart failure presenting in primary care. 10) NP levels may be helpful to screen for asymptomatic left ventricular dysfunction in high-risk patients.

BACKGROUND: Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. METHODS: From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression. RESULTS: During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96). CONCLUSIONS: In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.

Islet amyloid polypeptide (IAPP), a putative polypeptide hormone, is a product of pancreatic beta-cells and the major constituent of the amyloid deposits seen mainly in islets of type 2 diabetic humans and diabetic cats. The connection between IAPP amyloid formation and diabetes is unknown, but a limited segment of the IAPP molecule, positions 20-29, seems responsible for the aggregation to fibrils. Differences in the amino acid sequence of this region probably determine whether or not islet amyloid can develop in a particular species. Amyloid fibril formation can be mimicked in vitro with the aid of synthetic peptides. With this technique we show that peptides corresponding to IAPP positions 20-29 of human and cat, species that develop IAPP-derived islet amyloid, form amyloid-like fibrils in vitro. The corresponding IAPP segment from three rodent species that do not develop IAPP-derived amyloid did not give rise to fibrils. Substitution of the human IAPP-(20-29) decapeptide with one or two amino acid residues from species without islet amyloid generally reduced the capacity to form fibrils. We conclude that the sequence Ala-Ile-Leu-Ser-Ser, corresponding to positions 25-29 of human IAPP, is strongly amyloidogenic and that a proline-for-serine substitution in position 28, as in several rodents, almost completely inhibits formation of amyloid fibrils.

AIMS: The ESC-HF Pilot survey was aimed to describe clinical epidemiology and 1-year outcomes of outpatients and inpatients with heart failure (HF). The pilot phase was also specifically aimed at validating structure, performance, and quality of the data set for continuing the survey into a permanent Registry. METHODS: The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 Cardiology Centres in 12 European countries selected to represent the different health systems across Europe. All outpatients with HF and patients admitted for acute HF on 1 day per week for eight consecutive months were included. From October 2009 to May 2010, 5118 patients were included: 1892 (37%) admitted for acute HF and 3226 (63%) patients with chronic HF. The all-cause mortality rate at 1 year was 17.4% in acute HF and 7.2% in chronic stable HF. One-year hospitalization rates were 43.9% and 31.9%, respectively, in hospitalized acute and chronic HF patients. Major regional differences in 1-year mortality were observed that could be explained by differences in characteristics and treatment of the patients. CONCLUSION: The ESC-HF Pilot survey confirmed that acute HF is still associated with a very poor medium-term prognosis, while the widespread adoption of evidence-based treatments in patients with chronic HF seems to have improved their outcome profile. Differences across countries may be due to different local medical practice as well to differences in healthcare systems. This pilot study also offered the opportunity to refine the organizational structure for a long-term extended European network.

PURPOSE: To estimate the long-term (29-year) effect of mammographic screening on breast cancer mortality in terms of both relative and absolute effects. MATERIALS AND METHODS: This study was carried out under the auspices of the Swedish National Board of Health and Welfare. The board determined that, because randomization was at a community level and was to invitation to screening, informed verbal consent could be given by the participants when they attended the screening examination. A total of 133 065 women aged 40-74 years residing in two Swedish counties were randomized into a group invited to mammographic screening and a control group receiving usual care. Case status and cause of death were determined by the local trial end point committees and, independently, by an external committee. Mortality analysis was performed by using negative binomial regression. RESULTS: There was a highly significant reduction in breast cancer mortality in women invited to screening according to both local end point committee data (relative risk [RR] = 0.69; 95% confidence interval: 0.56, 0.84; P < .0001) and consensus data (RR = 0.73; 95% confidence interval: 0.59, 0.89; P = .002). At 29 years of follow-up, the number of women needed to undergo screening for 7 years to prevent one breast cancer death was 414 according to local data and 519 according to consensus data. Most prevented breast cancer deaths would have occurred (in the absence of screening) after the first 10 years of follow-up. CONCLUSION: Invitation to mammographic screening results in a highly significant decrease in breast cancer-specific mortality. Evaluation of the full impact of screening, in particular estimates of absolute benefit and number needed to screen, requires follow-up times exceeding 20 years because the observed number of breast cancer deaths prevented increases with increasing time of follow-up.