In 1968, an Ad Hoc committee at the Harvard Medical School advanced new criteria for determining death. It proposed that patients in irreversible coma with no discernible central nervous system activity were actually dead. The committee paved the way for the “whole brain” definition of death, which has reached broad public acceptance and legal enactment in many countries. Despite this, the philosophical and ethical debate about the “whole brain” definition of death is far from being closed. This paper analyses the ongoing controversy and evaluates the recent revision of the Swiss Academy of Medical Sciences guidelines for determining death.
The term acute kidney injury (AKI) has been recently coined by a large panel of international experts in place of the former expression “acute renal failure”. This change has been motivated by a double intention: first it served to definitely find a conventional definition for acute changes of renal function, previously lacking in the medical community. In fact, any attempt to compare scientific papers and different centres experiences on AKI was essentially impossible. The second aim was to remark that this syndrome is characterised by a spectrum of progressive damage, from mild creatinine increase to renal injury to a more severe form, failure: this important concept should increase clinicians awareness to every form of renal dysfunction, even milder ones, in order to improve epidemiologic analyses, potentially preventing eventual AKI progression and finally helping standardisation of medical and supportive therapy. This review will describe such “new era” of critical care nephrology by presenting current literature (and its many controversies) about AKI diagnosis, physiopathology and management.
Allergy and asthma are complex diseases influenced by many genes and molecular mechanisms. Recently a number of genome-wide association studies (GWAS) have investigated asthma- and allergy-related phenotypes. Results suggest the existence of sub phenotypes of asthma and document a need to better define the disease. Genetics may also help to identify groups of patients susceptible for specific forms of treatment and those at risk for adverse effects of therapy. Thus, genetics may represent a key tool to achieve individualised medicine in asthma and allergy in the future.
Upon reaction with electrons, oxygen is transformed into reactive oxygen species (ROS). It has long been known that ROS can destroy bacteria and destroy human cells, but research in recent decades has highlighted new roles for ROS in health and disease. Indeed, while prolonged exposure to high ROS concentrations may lead to non-specific damage to proteins, lipids, and nucleic acids, low to intermediate ROS concentrations exert their effects rather through regulation of cell signalling cascades. Biological specificity is achieved through the amount, duration, and localisation of ROS production. ROS have crucial roles in normal physiological processes, such as through redox regulation of protein phosphorylation, ion channels, and transcription factors. ROS are also required for biosynthetic processes, including thyroid hormone production and crosslinking of extracellular matrix. There are multiple sources of ROS, including NADPH oxidase enzymes; similarly, there are a large number of ROS-degrading systems. ROS-related disease can be either due to a lack of ROS (e.g., chronic granulomatous disease, certain autoimmune disorders) or a surplus of ROS (e.g., cardiovascular and neurodegenerative diseases). For diseases caused by a surplus of ROS, antioxidant supplementation has proven largely ineffective in clinical studies, most probably because their action is too late, too little, and too non-specific. Specific inhibition of ROS-producing enzymes is an approach more promising of clinical efficacy.
Prior to the introduction of chemotherapy, tuberculosis management relied upon aerotherapy, heliotherapy and good nutrition. This “treatment”, exemplified by the regimen applied in Swiss and other European mountain resorts, is described by Thomas Mann in the book “The Magic Mountain”. Tuberculosis chemotherapy began in 1944 with the introduction of streptomycin and para-amino-salicylic acid, later augmented by isoniazid. Early experience taught physicians that treatment must be given with multiple drugs to prevent emergence of resistance and that prolonged treatment adherence for 18–24 months was needed for a permanent cure of tuberculosis. Between 1970 and 1980 rifampicin was introduced and with pyrazinamide it made “short-course” treatment possible. For 30 years, a 6-month directly observed treatment short-course (DOTS) based on the three compounds isoniazid, rifampicin and pyrazinamide was the foundation of tuberculosis control strategies world-wide, and in recent years this was supplemented with ethambutol in view of increasing rates of isoniazid resistance. However, even 6 months of treatment is too long to easily ensure the compliance necessary to permanently cure tuberculosis. The recent spread of the HIV/AIDS epidemic has placed tuberculosis programmes under severe pressure and is accompanied by an increase in drug-resistance making tuberculosis virtually untreatable in some instances. In 2004 the first of a new generation of anti-tuberculosis drugs entered clinical evaluation. A series of clinical trials, often conducted at sites in Cape Town, South Africa, has shown them to be efficacious and hold promise of being able to shorten tuberculosis treatment and treat drug-resistant tuberculosis. Development and assessment of these drugs is ongoing but there is renewed hope that these new drugs and regimens will assist in finally conquering tuberculosis, preventing a return to Magic Mountain where sunshine and fresh air was all that could be offered to patients.
BACKGROUND: Goitre recurrence is a common problem following subtotal thyroid gland resection for multinodular goitre disease. The aim of the present study was to evaluate morbidity rate in relation to the side of initial and redo-surgery for recurrent disease.
METHODS: A total of 1699 patients underwent consecutive thyroid gland surgery between 1997 and 2010 at our institution. One hundred and eighteen patients (6.9%) underwent redo-surgery for recurrent disease after subtotal resection. One hundred and nine patients with complete follow-up were included in the present study.
RESULTS: Recurrent disease was found in 79 patients (72.5%) in the ipsilateral lobe and in 30 patients (27.5%) in the contralateral lobe. The incidence of permanent recurrent laryngeal nerve palsy was significantly higher in patients undergoing redo-surgery on the ipsilateral lobe compared to patients undergoing initial operation (3.8% vs. 1.1%; p = 0.03), whereas no difference was found in patients with contralateral redo-surgery compared to patients undergoing initial operation (p = 1.0). Independent risk factors for contralateral recurrent disease were age at primary operation <37 years (OR 4.86; 95% CI 1.58–15.01) and time to recurrence <20 years (OR 6.53; 95% CI 2.23–19.01).
CONCLUSION: Morbidity rate for recurrent disease after subtotal resection was significantly higher for ipsilateral redo-surgery compared to initial surgery, whereas redo-surgery can be performed safely on the contralateral lobe. Young age at primary operation and short time to recurrence are independent risk factors for contralateral recurrent disease.
AIM: Sustained elevation of resting heart rate (RHR) is thought to promote the initiation and progression of coronary artery disease (CAD). The aim of this paper is to test the hypothesis whether elevated RHR correlates with the presence and the extent of CAD in patients evaluated for CAD.
METHODS AND RESULTS: The association between RHR and CAD findings and myocardial perfusion SPECT (MPS) was tested in 1,465 patients. Patients with atrial fibrillation, pacemaker rhythm and treatment with negative chonotropic drugs were excluded. Standard scores for MPS evaluation were used.
CAD findings of myocardial ischaemia or scar were present in 408 patients (28%). The prevalence of CAD finding at MPS was not higher among patients with RHR above the median value of 79 bpm compared to patients with lower RHR (28% vs 28%; p = 1.00). The extent of myocardial ischaemia and scar did not increase with higher quartiles of RHR. In contrast, the presence of other established cardiovascular risk factors such as diabetes, male gender, more advanced age and presence of CAD symptoms such as angina and dyspnoea were independent predictors of CAD findings (p <0.05 for all).
CONCLUSION: Elevated RHR is not associated with the presence and the extent of CAD in patients evaluated for suspected but previously unknown CAD, suggesting that the impact of a higher RHR on mortality may be linked with other factors than only CAD itself.
QUESTIONS UNDER STUDY: To perform a cost-of-illness study of acute coronary syndrome (ACS) in Switzerland from a societal perspective, evaluating direct costs, production losses and intangible costs in terms of quality adjusted life years (QALYs) lost.
METHODS: A bottom-up incidence-based approach was used. Data concerning patients with one or more ACS events were extracted from a national hospital database and from mortality statistics. Inpatient costs included acute care and rehabilitation. Outpatient costs included costs for ambulance, visits to GP and cardiologist, outpatient diagnostics, medication and rehabilitation. Production losses included absenteeism, permanent disability and premature death. Intangible costs were calculated on previously published QALY weights. Cost data were derived from official price lists, literature and experts. Future costs and QALYs lost were discounted.
RESULTS: In 2008 14,955 patients experienced a total of 16,815 ACS events; 2,752 died as a consequence of these. The resulting 19,064 hospital stays had an average across-hospital length of stay of 9.1 days per patient. Total direct costs of ACS amounted to 630 Mio Swiss Francs (CHF) for society and CHF 462 Mio for health insurers. Total direct costs were dominated by costs of myocardial infarction: ST-elevation 45.8%, non-ST-elevation 35.8%. Production losses were CHF 519 Mio and intangible costs resulted in 49,878 QALYs lost.
CONCLUSIONS: ACS causes considerable costs in terms of direct medical expenditures, lost production, suffering and premature death, even without taking into account costs for its chronic consequences such as congestive heart failure.
PRINCIPLES: Cancer is disease of aging that disproportionately affects older adults and often results in considerable public health consequences. This study evaluated gender-age-specific cancer mortality risk factors in older adults in Switzerland with attention to the most common types of cancer.
METHODS: The population included all individuals ≥65 years old based on 1990/2000 censuses linked to mortality records through end of 2008. Cancer mortality relative risk was assessed by gender-age-specific all-cancer and cancer-specific mortality hazard ratios (HR) with 95% confidence intervals (CI) from adjusted Cox proportional hazards regression models.
RESULTS: The risk profile of dying from cancer was similar in older men and women across most socio-demographic characteristics: higher cancer mortality risk with lower educational attainment (all-cancer men HR = 0.84 [95%CI 0.82, 0.85] tertiary, HR = 1.09 [95%CI 1.07, 1.10] compulsory, women all-cancer HR = 0.95 [95%CI 0.92, 0.98] tertiary, HR = 1.03 [95%CI 1.02, 1.05] compulsory) and unmarried marital status. Cancer mortality risk factors varied less than hypothesised across older age-groups. However, for outcomes and characteristics with age-specific variation the oldest (≥85 years) generally showed the lower cancer mortality relative risk (except for non-Swiss lung cancer risk).
CONCLUSION: These comprehensive epidemiological results indicate that in Switzerland (like other developed countries) age alone is not the only important cancer risk factor and risk is not necessarily the same across older age-groups; providing additional needed information about the aging-cancer nexus. However, additional studies especially with consideration of stage of disease, treatments received and comorbidity are needed.
BACKROUND: Serum markers of inflammation and platelet activation are related to cardiovascular risk. Cardiovascular risk reduction is a major treatment goal in patients with peripheral arterial disease (PAD). Although current guidelines recommend supervised exercise training (SET) for PAD patients with intermittent claudication, its contribution to risk reduction remains unclear. Aim of the present study was to assess the impact of SET on inflammation and platelet activation as surrogates for cardiovascular risk.
METHODS: 53 patients with intermittent claudication were randomly assigned to SET on top of best medical treatment (BMT) for 6 months (SET-group) or to BMT only (BMT-group). High sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and fibrinogen as well as soluble P-selectin (sP-sel), prothrombin fragment 1+2 (F1.2) and monocyte-platelet aggregates (MPA) were determined at study entry, after 3, 6 and 12 months.
RESULTS: While clinical improvement, reflected by an increase of walking capacity, was observed upon SET, no lasting changes of markers of inflammation and platelet activation were found within the SET-group during the training period. Compared to the BMT-group no improvements of these markers were observed in response to training at any time point (all p >0.05).
CONCLUSION: Regular SET added no further anti-inflammatory effect and had no effect on platelet activation when provided on top of BMT in PAD patients with intermittent claudication.
QUESTIONS UNDER STUDY: Research on alcohol use disorders among physicians has been scarce in Germany. The aim of our study was to identify possible risk factors for alcohol use disorders among general practitioners (GPs) working in the outpatient sector in the federal German state of Rhineland-Palatinate (RP).
METHODS: An anonymous survey was carried out between June and July 2009. 2,092 practice-based GPs in the federal German state of RP were asked to take part in the cross-sectional study via postal mail. The CAGE screening tool was used in its German version (CAGE-G) to screen for alcohol use disorders (AUD). Moreover, possible risk factors such as work stress (effort-reward imbalance), stress experienced in the leisure time and personality characteristics (Type D personality, resilience) were included in the questionnaire.
RESULTS: 808 GPs participated (response rate 38.6%), n = 790 were eligible for the analysis. The frequency of AUD according to the CAGE-G was 18.9% (n = 149). Moreover, nearly one in four general practitioners reported consuming alcohol on a daily basis (23.0%, n = 182). In the logistic regression analyses, stress experienced in the leisure time was positively related to the occurrence of AUD, whereas resilience was negatively associated.
CONCLUSIONS: AUD as screened for by the CAGE-G was frequent in our sample of German GPs. Approaches to reduce their occurrence could comprise actions helping physicians to relieve stress in their leisure time. Furthermore, measures to increase physicians’ resilience by improving coping strategies might prove useful.
QUESTIONS: Three- and four-digit International Classification of Diseases (ICD-10) is not a reliable classification system in primary care. The reliability of the International Classification of Primary Care (ICPC-2) as an alternative coding system has not yet been investigated in a German general practice setting.
METHODS: Cross-sectional data were collected during a one year period in a general practice setting. Participants: A total of 8,877 patients were randomly selected. Main outcome measures: The first of the reasons for encounter was taken into account on new and chronic managed problems. The ICPC-2 coding of each case was performed by two raters to investigate the inter-rater agreement. The degree of agreement between the raters was assessed by using Cohen’s kappa (κ ≥ 0.61 meaning high or satisfactory and κ ≤ 0.6 (incl. ≤ 0.000) meaning low or unsatisfactory).
RESULTS: The reliability was good to excellent at the chapter level, at the component level the reliability was moderate though good in the components 1-symptoms and 7-diseases. At single code level the agreement was only fair to moderate in both chapters and components. One third to half of the used codes showed good inter-rater agreement.
CONCLUSION: The ICPC-2 is an adequate and feasible instrument for routine use in general practice. The fair to moderate reliability on the single code level should be considered when designing studies and interpreting data that are based on the ICPC-2.
QUESTIONS UNDER STUDY: The prevalence of diabetes mellitus in the older population is high, but hardly any data are available on current diabetes care in the primary care setting. We aimed at investigating the diabetes management of older patients with type 2 diabetes (T2DM) in the primary care setting, including adherence to current guidelines, comparing patients aged 70–79 years to those aged 80 years and above.
METHODS: From November 2008 through March 2009 a total of 23 primary care physicians and one consultant in internal medicine consecutively enrolled 203 unselected patients with T2DM aged ≥70 years.
RESULTS: From the 203 study participants 66% were 70–79 years of age, and 34% were 80 years or older. Mean HbA1c and LDL-cholesterol were not significantly different between the older and the younger age group (7.6 ± 1.6 vs. 7.1 ± 0.9%; p = 0.080; and 122 ± 40 vs. 114 ± 34 mg/dl; p = 0.273), whereas BMI was lower (27.5 ± 5.0 vs. 29.6 ± 5.0 kg/m2, p = 0.010), and the prevalent rates of coronary heart disease (55.1 vs. 37.1%, p = 0.011) and of dementia (29% vs. 6.1%, p = 0.001) were higher in the older age group. LDL-cholesterol (77.6% vs. 66.7%, p = 0.012), creatinine clearance (34.6% vs. 30.9%, p = 0.049) but not HbA1c (74.6% vs.73.9; p = 0.520) were monitored significantly less often in the older than in the younger age group.
CONCLUSIONS: While glycaemic control on average appears strict, there may be ample room for improvement in reaching lipid targets and in the monitoring of lipid and renal function among older adults in primary care, in particular among individuals aged ≥80 years.
QUESTIONS UNDER STUDY: This study investigated the use among the Swiss adult population and regional dissemination of various methods of complementary medicine (CM) provided by physicians or therapists in Switzerland.
METHODS: Data of the Swiss Health Survey 2007 were used, which comprised a telephone interview followed by a written questionnaire (18,760 and 14,432 respondents, respectively) and included questions about people's state of health, health insurance and usage of health services. Users and non-users of CM were compared using logistic regression models.
RESULTS: The most popular CM methods were homeopathy, osteopathy, acupuncture and shiatsu/foot reflexology. 30.5% of women and 15.2% of men used at least one CM method in the 12 months preceding the survey. Lake Geneva region and central Switzerland had more CM users than the other regions. Women, people between 25 and 64 years of age and people with higher levels of education were more likely to use CM. 53.5% of the adult population had a supplemental health insurance for CM treatments. 32.9% of people with such an insurance used CM during the 12 months preceding the survey, and so did 12.0% of people without additional insurance.
CONCLUSIONS: Almost one fourth of the Swiss adult population had used CM within the past 12 months. User profiles were comparable to those in other countries. Despite a generally lower self-perceived health status, elderly people were less likely to use CM.
PRINCIPLES: It is crucial for aging societies to evaluate trends in cancer mortality rates of older adults. This study examined socio-demographic and regional characteristics specifically focused on the cancer mortality experience of older adults in Switzerland.
METHODS: This study included all individuals ≥65 years based on 1990/2000 censuses linked to mortality records to end of 2008 in the Swiss National Cohort. Gender-age-specific (<65, 65–74, 75–84, 85+ years) mortality rates were calculated as observed (cancer deaths/person years) and expected from Poisson models adjusted for changes in death record coding over follow-up.
RESULTS: Cancer mortality, except for lung cancer, increased with advancing age. Older men in all age groups had overall higher cancer mortality rates than older women and showed a consistent decline in all-cancer mortality (age 65–74 years 1991 rate ratio (RR) = 1.13 [95%CI 1.08, 1.19]; 2008 RR = 0.88 [95%CI 0.86, 0.90], compared to rates 2000). In contrast, older women in all age groups showed early declines with a levelling-off of all-cancer mortality beginning in 2000 (age 65–74 years 1991 RR = 1.20 [95%CI 1.14, 1.27]; 2008 RR = 0.96 [95%CI 0.93, 0.98], compared to rates 2000). For older men there appeared to be an education effect for all-cancer and lung cancer mortality; highest rates in older men with compulsory education. Younger old women living alone or in suburban areas had the most sharpest increase in lung cancer mortality rates.
CONCLUSION: This comprehensive epidemiological analysis of cancer mortality trends in older adults provides further evidence that in Switzerland (like other developed countries) cancer is a disease of aging with important gender-age-specific variations representing major public health challenges for aging societies.