The origin of the European Medieval Warm Period"

Proxy records and results of a three dimensional climate model show that European summer temperatures roughly a millennium ago were comparable to those of the last 25 years of the 20th century, supporting the existence of a summer "Medieval Warm Period" in Europe. Those two relatively mild periods were separated by a rather cold era, often referred to as the "Little Ice Age". Our modelling results suggest that the warm summer conditions during the early second millennium compared to the climate background state of the 13th–18th century are due to a large extent to the long term cooling induced by changes in land-use in Europe. During the last 200 years, the effect of increasing greenhouse gas concentrations, which was partly levelled off by that of sulphate aerosols, has dominated the climate history over Europe in summer. This induces a clear warming during the last 200 years, allowing summer temperature during the last 25 years to reach back the values simulated for the early second millennium. Volcanic and solar forcing plays a weaker role in this comparison between the last 25 years of the 20th century and the early second millennium. Our hypothesis appears consistent with proxy records but modelling results have to be weighted against the existing uncertainties in the external forcing factors, in particular related to land-use changes, and against the uncertainty of the regional climate sensitivity. Evidence for winter is more equivocal than for summer. The forced response in the model displays a clear temperature maximum at the end of the 20th century. However, the uncertainties are too large to state that this period is the warmest of the past millennium in Europe during winter.

ABO histo-blood group antigen expression on the graft endothelium long term after ABO-compatible, non-identical heart transplantation

We recently reported a complete change in the endothelial ABO histo-blood group phenotype of a cardiac allograft long term after B to O mismatched transplantation. In the context of the current controversy on graft recolonization with recipient endothelial cells and its importance in the development of immunological unresponsiveness, we monitored the expression of endothelial ABH histo-blood group antigens of 10 ABO-compatible, non-identical cardiac allografts over an observation period of at least 30 months. ABH antigens as well as markers for endothelial cells, erythrocytes and thrombocytes were investigated retrospectively by immunohistochemistry using monoclonal antibodies on sections of formalin-fixed, paraffin-embedded biopsies and were evaluated semi-quantitatively by microscopy. In contrast to our earlier finding of the change in the endothelial ABO histo-blood group phenotype long term after ABO- mismatched transplantation, we could not confirm this change in 10 compatible but non-identical cases.

Short- and long-term skeletal relapse after mandibular advancement surgery

This study analyzes short- and long-term skeletal relapse after mandibular advancement surgery and determines its contributing factors. Thirty-two consecutive patients were treated for skeletal Class II malocclusion during the period between 1986 and 1989. They all had combined orthodontic and surgical treatment with BSSO and rigid fixation excluding other surgery. Of these, 15 patients (47%) were available for a long-term cephalography in 2000. The measurement was performed based on the serial cephalograms taken preoperatively; 1 week, 6 months and 14 months postoperatively; and at the final evaluation after an average of 12 years. Mean mandibular advancement was 4.1 mm at B-point and 4.9 mm at pogonion. Representing surgical mandibular ramus displacement, gonion moved downwards 2 mm immediately after surgery. During the short-term postoperative period, mandibular corpus length decreased only 0.5 mm, indicating that there was no osteotomy slippage. After the first year of observation, skeletal relapse was 1.3 mm at B-point and pogonion. The relapse continued, reaching a total of 2.3 mm after 12 years, corresponding to 50% of the mandibular advancement. Mandibular ramus length continuously decreased 1 mm during the same observation period, indicating progressive condylar resorption. No significant relationship between the amount of initial surgical advancement and skeletal relapse was found. Preoperative high mandibulo-nasal plane (ML-NL) angle appears to be associated with long-term skeletal relapse.

High-dose intravenous immunoglobulin pulse therapy in patients with progressive immunoglobulin A nephropathy: a long-term follow-up

In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from -1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P = 0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN.

Are there accurate predictors of long-term vital and functional outcomes in cardiac surgical patients requiring prolonged intensive care?

BACKGROUND AND OBJECTIVE: The decision to maintain intensive treatment in cardiac surgical patients with poor initial outcome is mostly based on individual experience. The risk scoring systems used in cardiac surgery have no prognostic value for individuals. This study aims to assess (a) factors possibly related to poor survival and functional outcomes in cardiac surgery patients requiring prolonged (> or = 5 days) intensive care unit (ICU) treatment, (b) conditions in which treatment withdrawal might be justified, and (c) the patient's perception of the benefits and drawbacks of long intensive treatments. METHODS: The computerized data prospectively recorded for every patient in the intensive care unit over a 3-year period were reviewed and analyzed (n=1859). Survival and quality of life (QOL) outcomes were determined in all patients having required > or =5 consecutive days of intensive treatment (n=194/10.4%). Long-term survivors were interviewed at yearly intervals in a standardized manner and quality of life was assessed using the dependency score of Karnofsky. No interventions or treatments were given, withhold, or withdrawn as part of this study. RESULTS: In-hospital, 1-, and 3-year cumulative survival rates reached 91.3%, 85.6%, and 75.1%, respectively. Quality of life assessed 1 year postoperatively by the score of Karnofsky was good in 119/165 patients, fair in 32 and poor in 14. Multivariate logistic regression analysis of 19 potential predictors of poor outcome identified dialysis as the sole factor significantly (p=0.027) - albeit moderately - reducing long-term survival, and sustained neurological deficit as an inconstant predictor of poor functional outcome (p=0.028). One year postoperatively 0.63% of patients still reminded of severe suffering in the intensive station and 20% of discomfort. Only 7.7% of patients would definitely refuse redo surgery. CONCLUSIONS: This study of cardiac surgical patients requiring > or =5 days of intensive treatment did not identify factors unequivocally justifying early treatment limitation in individuals. It found that 1-year mortality and disability rates can be maintained at a low level in this subset of patients, and that severe suffering in the ICU is infrequent.

Long-term outcome after structural failure of rotator cuff repairs

BACKGROUND: In a previous study, twenty consecutive patients with a rerupture of the rotator cuff, as documented with magnetic resonance imaging, were found to have significantly less pain and better function and strength, compared with the preoperative state, at 3.2 years postoperatively. It was the purpose of this study to determine the clinical and structural outcomes of these reruptures in the same twenty patients after a longer period of follow-up. METHODS: At a mean of 7.6 years postoperatively, the twenty patients were reexamined clinically and with standard radiographs and magnetic resonance imaging with use of the same clinical, radiographic, and magnetic resonance imaging criteria as were utilized in the review at 3.2 years. The mean age at the time of final follow-up was sixty-six years. RESULTS: Nineteen of the twenty patients continued to be either very satisfied or satisfied with the outcome. The relative Constant score averaged 88% and was not significantly different from the score at 3.2 years, which averaged 83%. The mean scores for pain, function, and strength also had not changed significantly. Overall, the twenty reruptures had not increased in size, and eight of them had healed structurally at the time of the 7.6-year follow-up. Seven of these eight reruptures had been of the supraspinatus tendon only, and seven had been smaller than 400 mm(2) at 3.2 years. Twelve reruptures persisted, and five were larger than the preoperative tear. Fatty infiltration of the infraspinatus muscle progressed significantly (p = 0.015) and the acromiohumeral distance decreased significantly (p = 0.006) between the two follow-up periods. Neither fatty infiltration of the supraspinatus and subscapularis muscles nor glenohumeral osteoarthritis progressed significantly. CONCLUSIONS: At an average of 7.6 years, the clinical outcomes after structural failure of rotator cuff repairs remained significantly improved over the preoperative state in terms of pain, function, strength, and patient satisfaction. Overall, the reruptures that had been present at 3.2 years did not increase in size. We also found that reruptures of the supraspinatus that had been smaller than 400 mm(2) had the potential to heal.

[Influence of local anaesthesia on short- and long-term pain induced in calves by three bloodless castration methods]

Behavioural and cortisol responses of calves were used as indicators of pain to assess short- and long-term effects of three bloodless castration methods with and without local anaesthesia. Eighty calves, aged 21 to 28 days, were control handled (20) or castrated by Burdizzo (25), rubber ring (25), or crushing technique (10). Either a total volume of 10 ml of Lidocaine or NaCl was distributed in both spermatic cords and the scrotal neck. The plasma cortisol response was monitored for 72 hours, and behavioural and clinical traits over a three-month period. Castration success was assessed by degree of atrophy and histological tissue examination. The crushing technique cannot be recommended due to incomplete castration success, and the evaluation was stopped after 10 animals. Local anaesthesia reduced the level of indicators of acute pain after Burdizzo and rubber ring technique. It did, however, not result in a totally painless castration. When castration is performed at the age of 3 to 4 weeks, the rubber ring but not the Burdizzo method showed evidence of chronic pain lasting for several weeks.

Effect of local anaesthesia on short- and long-term pain induced by two bloodless castration methods in calves

Behavioural and cortisol responses of calves were used as indicators of pain to assess short- and long-term effects of bloodless castration methods with and without local anaesthesia. Seventy calves, aged 21-28 days, were control handled (20) or castrated using the Burdizzo (25) or rubber ring technique (25). Either 10 mL lidocaine or NaCl were distributed in both spermatic cords and the scrotal neck. The plasma cortisol response was recorded for 72 h, and behavioural and clinical traits monitored over a three month period. Local anaesthesia reduced the level of indicators of acute pain after both the Burdizzo and rubber ring techniques. It did not, however, result in a totally painless castration. As there was evidence of chronic pain lasting for several weeks after rubber ring castration, the Burdizzo method is judged to be preferable to the rubber ring technique.

A systematic review of the survival and complication rates of resin-bonded bridges after an observation period of at least 5 years

OBJECTIVES: The objectives of this systematic review were to assess the 5-year survival of resin-bonded bridges (RBBs) and to describe the incidence of technical and biological complications. METHODS: An electronic Medline search complemented by manual searching was conducted to identify prospective and retrospective cohort studies on RBBs with a mean follow-up time of at least 5 years. Patients had to have been examined clinically at the follow-up visit. Assessment of the identified studies and data extraction were performed independently by two reviewers. Failure and complication rates were analyzed using random-effects Poissons regression models to obtain summary estimates of 5-year proportions. RESULTS: The search provided 6110 titles and 214 abstracts. Full-text analysis was performed for 93 articles, resulting in 17 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated survival of RBBs of 87.7% (95% confidence interval (CI): 81.6-91.9%) after 5 years. The most frequent complication was debonding (loss of retention), which occurred in 19.2% (95% CI: 13.8-26.3%) of RBBs over an observation period of 5 years. The annual debonding rate for RBBs placed on posterior teeth (5.03%) tended to be higher than that for anterior-placed RBBs (3.05%). This difference, however, did not reach statistical significance (P=0.157). Biological complications, like caries on abutments and RBBs lost due to periodontitis, occurred in 1.5% of abutments and 2.1% of RBBs, respectively. CONCLUSION: Despite the high survival rate of RBBs, technical complications like debonding are frequent. This in turn means that a substantial amount of extra chair time may be needed following the incorporation of RBBs. There is thus an urgent need for studies with a follow-up time of 10 years or more, to evaluate the long-term outcomes.

Patient self-management of long-term oral anticoagulation in Switzerland

Indications for oral anticoagulation (OAC) have increased in recent years. OAC requires frequent monitoring of the prothrombin time to keep the intensity within the therapeutic range and to minimise the risk for complications. Patient self-management (PSM) has been found to improve the quality of OAC. The present study aimed to investigate the first 330 patients performing PSM in Switzerland. A questionnaire was sent to all patients who followed a teaching program for PSM of OAC between 1998 and 2003. Moreover, family physicians were contacted and/or discharge letters were obtained from the hospitals or the treating physicians. During the study period 13 patients died. Out of the 300 patients providing information 254 (85%) still perform PSM. At least one INR determination per two weeks was done by 74% of the patients and 25% performed at least one INR measurement every 15-30 days. The median time spent within the individual INR target range was 72%. No thromboembolic complications occurred, however, among the 13 patients who died, 1 had myocardial infarction and 6 died of heart failure. When counting these events as arterial thromboembolic complications the frequency was 0.6 (95% CI: 0.3-1.3) per 100 patient-years. The frequency of major bleeding was 0.6 (95% CI: 0.2-1.3) per 100 patient-years. We conclude from this study investigating a real-world patient collective that PSM is suitable and safe for the patients identified by their family physicians and successfully trained by our training centre.

Transient apical ballooning syndrome--clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population

BACKGROUND: Transient apical ballooning syndrome (TABS) or Takotsubo cardiomyopathy mimics acute ST-elevation myocardial infarction, but is considered to have a good prognosis with only moderate elevation of myocardial enzymes and full recovery of left ventricular function. Although it is increasingly reported, its exact incidence, clinical presentation, and prognosis in non-Asian populations remain largely unknown. OBJECTIVE: To describe the clinical characteristics and long-term follow-up of patients who presented with TABS at our institution over a 3 year-period. METHODS: Patients were retrospectively retrieved from our local database. Patient charts were carefully reviewed and the diagnosis of TABS was based on the Mayo Clinic diagnostic criteria. Moreover, psychosocial stress or gastrointestinal disease was recorded. RESULTS: During the study period, 13,715 coronary angiographies were performed at our institution, including 2459 patients presenting with an acute coronary syndrome (ACS). Forty-one TABS were diagnosed, which represents an incidence of 1.7% of ACS-patients and 0.3% of all coronary angiographies performed, respectively. Mean age was 65 years, with 85% women. Clinical presentations included chest pain, dyspnoea, and cardiogenic shock. A preceding psychological or physical condition perceived as "stress" was reported in 61%. At a mean follow-up of 675+/-288 days, none of the patients died of cardiac causes, but two patients had a recurrence of symptoms. CONCLUSIONS: This is the largest cohort of TABS patients reported out of Europe so far. The good overall prognosis and low likelihood of recurrence were confirmed.

Obesity in long-term survivors of childhood acute lymphoblastic leukemia

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates reaching 80% emphasizes the necessity to determine treatment related long-term effects. The present study examines the prevalence of and the risk factors for overweight and obesity in a cohort of ALL survivors treated and living in the French speaking part of Switzerland. METHODS: In this retrospective two-center study, height and weight of 54 patients diagnosed with ALL in first complete remission and treated with chemotherapy only were recorded at specified time points during treatment and off-therapy. Body mass index (BMI) and its age- and gender-adjusted standard deviation score (BMI-SDS) were calculated for the patients and their parents separately. Overweight and obesity were defined by a threshold of BMI-SDS >1.645 and BMI-SDS >1.96, respectively. RESULTS: At last follow-up, 16 (30%) of the 54 survivors were overweight and 10 (18%) were obese. The off-treatment period was most at risk with 11 of the 16 becoming overweight and 9 of the 10 becoming obese during that period. Overweight/obesity at diagnosis and abnormal maternal BMI were significantly associated with abnormal weight at follow-up, while age at diagnosis, gender, cumulative dose of steroids and paternal BMI showed no association. CONCLUSIONS: Consistent with published evidence from other regions of the developed and developing world, there is a significant prevalence of obesity in young ALL survivors in the French speaking part of Switzerland. Factors significantly associated with this late effect were mostly related to the familial background rather than to the treatment components.

Fluctuation analysis of lung function as a predictor of long-term response to beta2-agonists

The response to beta(2)-agonists differs between asthmatics and has been linked to subsequent adverse events, even death. Possible determinants include beta(2)-adrenoceptor genotype at position 16, lung function and airway hyperresponsiveness. Fluctuation analysis provides a simple parameter alpha measuring the complex correlation properties of day-to-day peak expiratory flow. The present study investigated whether alpha predicts clinical response to beta(2)-agonist treatment, taking into account other conventional predictors. Analysis was performed on previously published twice-daily peak expiratory flow measurements in 66 asthmatic adults over three 6-month randomised order treatment periods: placebo, salbutamol and salmeterol. Multiple linear regression was used to determine the association between alpha during the placebo period and response to treatment (change in the number of days with symptoms), taking into account other predictors namely beta(2)-adrenoceptor genotype, lung function and its variability, and airway hyperresponsiveness. The current authors found that alpha measured during the placebo period considerably improved the prediction of response to salmeterol treatment, taking into account genotype, lung function or its variability, or airway hyperresponsiveness. The present study provides further evidence that response to beta(2)-agonists is related to the time correlation properties of lung function in asthma. The current authors conclude that fluctuation analysis of lung function offers a novel predictor to identify patients who may respond well or poorly to treatment.

A new instrument for pain assessment in the immediate postoperative period

Perceptual-cognitive impairment after general anaesthesia may affect the ability to reliably report pain severity with the standard visual analog scale (VAS). To minimise these limitations, we developed 'PAULA the PAIN-METER' (PAULA): it has five coloured emoticon faces on the forefront, it is twice as long as a standard VAS scale, and patients use a slider to mark their pain experience. Forty-eight postoperative patients rated descriptive pain terms on PAULA and on a standard VAS immediately after admission and before discharge from the postanaesthesia care unit. Visual acuity was determined before both assessments. The values obtained with PAULA showed less variance than those obtained with the standard VAS, even at the first assessment, where only 23% of the patients had regained their visual acuity. Furthermore, the deviations of the absolute VAS values in individual patients for each descriptive pain term were significantly smaller with PAULA than with the standard VAS.

SEARCH FOR LONG-LIVED WEAKLY INTERACTING PARTICLES USING THE PIERRE AUGER OBSERVATORY

Data collected with the surface detector array of the Pierre Auger Observatory during the period from January 1, 2004 to March 17, 2015 was examined for evidence of production of long-lived weakly interacting particles in interactions of ultra high energy cosmic rays in the atmosphere. The search was performed using extensive air showers with primary energies more than 10 EeV and arrival directions in the range of 57.5◦ to 77.5◦. There was no evidence of significant production of such particles. An upper limit on the fraction of extensive air showers in which such particles are produced was set.