Chapter I: Definitions, epidemiology, clinical presentation and prognosis

The concept of chronic critical limb ischaemia (CLI) emerged late in the history of peripheral arterial occlusive disease (PAOD). The historical background and changing definitions of CLI over the last decades are important to know in order to understand why epidemiologic data are so difficult to compare between articles and over time. The prevalence of CLI is probably very high and largely underestimated, and significant differences exist between population studies and clinical series. The extremely high costs associated with management of these patients make CLI a real public health issue for the future. In the era of emerging vascular surgery in the 1950s, the initial classification of PAOD by Fontaine, with stages III and IV corresponding to CLI, was based only on clinical symptoms. Later, with increasing access to non-invasive haemodynamic measurements (ankle pressure, toe pressure), the need to prove a causal relationship between PAOD and clinical findings suggestive of CLI became a real concern, and the Rutherford classification published in 1986 included objective haemodynamic criteria. The first consensus document on CLI was published in 1991 and included clinical criteria associated with ankle and toe pressure and transcutaneous oxygen pressure (TcPO(2)) cut-off levels <50 mmHg, <30 mmHg and <10 mmHg respectively). This rigorous definition reflects an arterial insufficiency that is so severe as to cause microcirculatory changes and compromise tissue integrity, with a high rate of major amputation and mortality. The TASC I consensus document published in 2000 used less severe pressure cut-offs (≤ 50-70 mmHg, ≤ 30-50 mmHg and ≤ 30-50 mmHg respectively). The thresholds for toe pressure and especially TcPO(2) (which will be also included in TASC II consensus document) are however just below the lower limit of normality. It is therefore easy to infer that patients qualifying as CLI based on TASC criteria can suffer from far less severe disease than those qualifying as CLI in the initial 1991 consensus document. Furthermore, inclusion criteria of many recent interventional studies have even shifted further from the efforts of definition standardisation with objective criteria, by including patients as CLI based merely on Fontaine classification (stage III and IV) without haemodynamic criteria. The differences in the natural history of patients with CLI, including prognosis of the limb and the patient, are thus difficult to compare between studies in this context. Overall, CLI as defined by clinical and haemodynamic criteria remains a severe condition with poor prognosis, high medical costs and a major impact in terms of public health and patients' loss of functional capacity. The major progresses in best medical therapy of arterial disease and revascularisation procedures will certainly improve the outcome of CLI patients. In the future, an effort to apply a standardised definition with clinical and objective haemodynamic criteria will be needed to better demonstrate and compare the advances in management of these patients.

Tradeoffs or Synergies? Assessing Local and Regional Food Aid Procurement through Case Studies in Burkina Faso and Guatemala

We compare the impacts across a range of criteria of local and regional procurement (LRP) relative to transoceanic shipment of food aid in Burkina Faso and Guatemala. We find that neither instrument dominates the other across all criteria in either country, although LRP commonly performs at least as well as transoceanic shipment with respect to timeliness, cost, market price impacts, satisfying recipients' preferences, food quality and safety, and in benefiting smallholder suppliers. LRP is plainly a valuable food assistance tool, but its advantages and disadvantages must be carefully weighed, compared, and prioritized depending on the context and program objectives. (C) 2013 Elsevier Ltd. All rights reserved.

Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

Background Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. Objectives We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) comparing chemotherapy alone with CMT in patients with early stage Hodgkin lymphoma with respect to response rate, progression-free survival (alternatively tumour control) and overall survival (OS). Search methods We searched MEDLINE, EMBASE and CENTRAL as well as conference proceedings from January 1980 to November 2010 for randomised controlled trials comparing chemotherapy alone to the same chemotherapy regimen plus radiotherapy. Selection criteria Randomised controlled trials comparing chemotherapy alone with CMT in patients with early stage HL. Trials in which the chemotherapy differed between treatment arms were excluded. Trials with more than 20% of patients in advanced stage were also excluded. Data collection and analysis Effect measures used were hazard ratios (HR) for tumour control and OS as well as relative risks for response rates. Two review authors independently extracted data and assessed quality of trials. We contacted study authors to obtain missing information. Since none of the trials reported progression-free survival according to our definitions, all similar outcomes were evaluated as tumour control. Main results Five RCTs involving 1245 patients were included. The HR was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumour control and 0.40 (95% CI 0.27 to 0.61) for OS for patients receiving CMT compared to chemotherapy alone. Complete response rates were similar between treatment groups. In sensitivity analyses another six trials were included that did not fulfil the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. Authors' conclusions Adding radiotherapy to chemotherapy improves tumour control and overall survival in patients with early stage Hodgkin lymphoma.

Is the metabolic syndrome a new childhood disease?

Overweight and obesity in children and adolescents have become a major public health problem in recent years throughout the world. The medical consequences of obesity may manifest as an increase in the prevalence of the metabolic syndrome in children and adolescents putting them at increased risk for future cardiovascular diseases. Obesity can cause insulin resistance and might disturb glucose homeostasis eventually leading to type 2 diabetes in susceptible patients. Insulin resistance is also involved in the pathogenesis of dyslipidemia in obese children characteristically presenting as hypertriglyceridemia and low HDL cholesterol. Even elevated blood pressure might be present in obese kids. Here we present a 12-year-old boy diagnosed with the metabolic syndrome. The diagnostic criteria of the metabolic syndrome in children and adolescents are discussed. Thoughts about pathophysiology and therapeutic options are offered.

Internet based multicenter study for thoracolumbar injuries: a new concept and preliminary results

This article reports about the internet based, second multicenter study (MCS II) of the spine study group (AG WS) of the German trauma association (DGU). It represents a continuation of the first study conducted between the years 1994 and 1996 (MCS I). For the purpose of one common, centralised data capture methodology, a newly developed internet-based data collection system ( http://www.memdoc.org ) of the Institute for Evaluative Research in Orthopaedic Surgery of the University of Bern was used. The aim of this first publication on the MCS II was to describe in detail the new method of data collection and the structure of the developed data base system, via internet. The goal of the study was the assessment of the current state of treatment for fresh traumatic injuries of the thoracolumbar spine in the German speaking part of Europe. For that reason, we intended to collect large number of cases and representative, valid information about the radiographic, clinical and subjective treatment outcomes. Thanks to the new study design of MCS II, not only the common surgical treatment concepts, but also the new and constantly broadening spectrum of spine surgery, i.e. vertebro-/kyphoplasty, computer assisted surgery and navigation, minimal-invasive, and endoscopic techniques, documented and evaluated. We present a first statistical overview and preliminary analysis of 18 centers from Germany and Austria that participated in MCS II. A real time data capture at source was made possible by the constant availability of the data collection system via internet access. Following the principle of an application service provider, software, questionnaires and validation routines are located on a central server, which is accessed from the periphery (hospitals) by means of standard Internet browsers. By that, costly and time consuming software installation and maintenance of local data repositories are avoided and, more importantly, cumbersome migration of data into one integrated database becomes obsolete. Finally, this set-up also replaces traditional systems wherein paper questionnaires were mailed to the central study office and entered by hand whereby incomplete or incorrect forms always represent a resource consuming problem and source of error. With the new study concept and the expanded inclusion criteria of MCS II 1, 251 case histories with admission and surgical data were collected. This remarkable number of interventions documented during 24 months represents an increase of 183% compared to the previously conducted MCS I. The concept and technical feasibility of the MEMdoc data collection system was proven, as the participants of the MCS II succeeded in collecting data ever published on the largest series of patients with spinal injuries treated within a 2 year period.

Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study

BACKGROUND: Chronic idiopathic urticaria (CIU) is defined by the almost daily presence of urticaria for at least 6 weeks without an identifiable cause. Symptoms include short-lived wheals, itching, and erythema. CIU impedes significantly a patient's quality of life (QoL). Levocetirizine is an antihistamine from the latest generation approved for CIU. AIM: To investigate the efficacy of levocetirizine, 5 mg, and placebo for the symptoms and signs of CIU, as well as for the QoL and productivity. METHODS: The primary criteria of evaluation were the pruritus severity scores over 1 week of treatment and over 4 weeks. The QoL was assessed via the Dermatology Life Quality Index (DLQI). RESULTS: Baseline pruritus severity scores were comparable in the two treatment groups (2.06+/-0.58). After 1 week, levocetirizine was superior to placebo and demonstrated a considerable efficacy (difference=0.78, P<0.001). This efficacy was maintained over the entire study period (4 weeks, P<0.001). The number and size of wheals were considerably reduced compared with placebo over 1 week and over the total treatment period (P

Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study (SPR Study): recruitment list evaluation. Study report no. 2

BACKGROUND: Accompanying the patient recruitment within the "Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment multicentre trial (SPR)", all patients with primary rhegmatogenous retinal detachment (RRD) had to be documented in a detailed recruitment list. The main goal of this analysis was to estimate the prevalence of "medium-severe" RRD (SPR Study eligible) as defined by the SPR Study inclusion criteria. In addition, the detailed anatomical situation of medium-severe RRD is investigated. METHODS: SPR Study recruitment was evaluated via a standardised questionnaire, which contained a coloured fundus drawing and information regarding possible reasons for exclusion from the SPR Study in each case. A team of three experienced vitreoretinal surgeons evaluated all fundus drawings from a 1-year period. The review led to a decision on SPR Study eligibility on the pure basis of anatomical assessment. The main outcome measures were assessment of feasible inclusion into the SPR Study by the evaluation team based on the fundus drawing and anatomical details. RESULTS: A total of 1,115 patients with RRD from 13 European centres were prospectively enrolled in the year 2000. The quality of the drawings sufficed for assessment in 1,107 cases (99.3%). Three hundred and twelve fundus drawings (28.2%) met the anatomic inclusion criteria of the SPR Study. RRD of medium severity is characterised by an average number of 2.6 (SD 2.4) retinal breaks, 5.8 (SD 2.8) clock hours of detached retina, unclear hole situation in 15.1% of cases (n=47), attached macula in 42.9% (n=134), bullous detachment in 15.1% (n=47) and vitreous haemorrhage/opacity in 7.7% (n=24). CONCLUSIONS: In the recruitment lists of the SPR Study of the year 2000, RRD of medium severity was present in nearly one third of the patients with primary RRD. These findings emphasise the clinical relevance of the SPR Study.

Allergic bronchopulmonary aspergillosis: the hunt for a diagnostic serological marker in cystic fibrosis patients

The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis patients remains challenging, mainly owing to overlapping symptoms of the underlying lung disease with clinical symptoms of ABPA. In addition, a varying mixture of diagnostic criteria, including clinical status, radiological findings and immunological measurements, has led to confusion and differing recommendations. In order to help simplify as well as standardize the diagnostic criteria for ABPA, different serological markers have been evaluated in the last 20 years and their usefulness has been assessed in many clinical studies. This review presents current diagnostic criteria of ABPA, with a special focus on serum markers supporting the diagnosis and explains why the hunt for a serological marker for ABPA is still ongoing.

Low serum alpha-tocopherol and selenium are associated with accelerated apoptosis in severe sepsis

During sepsis, a severe systemic disorder, micronutrients often are decreased. Apoptosis is regarded as an important mechanism in the development of often significant immunosuppression in the course of the disease. This study aimed to investigate alpha-tocopherol and selenium in reference to apoptosis in patients with sepsis. 16 patients were enrolled as soon as they fulfilled the criteria of severe sepsis. 10 intensive care patients without sepsis and 11 healthy volunteers served as controls. alpha-Tocopherol, selenium and nucleosomes were measured in serum. Phosphatidylserine externalization and Bcl-2 expression were analyzed in T-cells by flow cytometry. Serum alpha-tocopherol and selenium were decreased in severe sepsis but not in non-septic critically ill patients (p < 0.05). Conversely, markers of apoptosis were increased in sepsis but not in critically ill control patients: Nucleosomes were found to be elevated 3 fold in serum (p < 0.05) and phosphatidylserine was externalized on an expanded subpopulation of T-cells (p < 0.05) while Bcl-2 was expressed at lower levels (p < 0.05). The decrease of micronutrients correlated with markers of accelerated apoptosis. Accelerated apoptosis in sepsis is associated with low alpha-tocopherol and selenium. The results support the investigation of micronutrient supplementation strategies in severe sepsis.

WATER ACCESS AND MAINTENANCE IN KARONGA, MALAWI

This report is a case study of how Mwangalala community accesses water and how that access is maintained. Mwangalala community is located in the northern tip of Karonga district in Malawi, Africa. The case study evaluates how close the community is to meeting target 10 of the Millennium Development Goals, sustainable access to safe drinking water, and evaluates the current water system through Human Centered Design’s criteria of desirability, feasibility, and viability. It also makes recommendations to improve water security in Mwangalala community. Data was collected through two years of immersive observation, interviews with 30 families, and observing two wells on three separate occasions. The 30 interviews provided a sample size of over 10% of the community’s population. Participants were initially self-selected and then invited to participate in the research. I walked along community pathways and accepted invitations to join casual conversations in family compounds. After conversing I asked the family members if they would be willing to participate in my research by talking with me about water. Data collected from the interviews and the observations of two wells were compared and analyzed for common themes. Shallow wells or open wells represented the primary water source for 93% of interview participants. Boreholes were also present in the community, but produced unpalatable water due to high concentrations of dissolved iron and were not used as primary water sources. During observations 75% of community members who used the shallow well, primarily used for consumptive uses like cooking or dinking, were females. Boreholes were primarily used for non-consumptive uses such as watering crops or bathing and 77% of the users were male. Shallow wells could remain in disrepair for two months because the repairman was a volunteer, who was not compensated for the skilled labor required to repair the wells. Community members thought the maintenance fee went towards his salary, so did not compensate the repairman when he performed work. This miscommunication provided no incentive for the repairman to make well repairs a priority, and left community members frustrated with untimely repairs. Shallow wells with functional pumps failed to provide water when the water table levels drop during dry season, forcing community members to seek secondary or tertiary water sources. Open wells, converted from shallow wells after community members did not pay for repairs to the pump, represented 44% of the wells originally installed with Mark V hand pumps. These wells whose pumps were not repaired were located in fields and one beside a church. The functional wells were all located on school grounds or in family compounds, where responsibility for the well’s maintenance is clearly defined. Mwangalala community fails to meet Millennium Development goals because the wells used by the community do not provide sustainable access to safe drinking water. Open wells, used by half the participants in the study, lack a top covering to prevent contamination from debris and wildlife. Shallow well repair times are unsustainable, taking longer than two weeks to be repaired, primarily because the repair persons are expected to provide skilled labor to repair the wells without compensation. Improving water security for Mwangalala can be achieved by improving repair times on shallow wells and making water from boreholes palatable. There are no incentives for a volunteer repair person to fix wells in a timely manner. Repair times can be improved by reducing the number of wells a repair person is responsible for and compensating the person for the skilled labor provided. Water security would be further improved by removing iron particulates from borehole water, thus rendering it palatable. This is possible through point of use filtration utilizing ceramic candles; this would make pumped water available year-round.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

Zur Versicherbarkeit von zukünftigen Katastrophen

Natur- und Man-made-Katastrophen nehmen quantitativ an Bedeutung zu. Im vorliegenden Beitrag diskutieren wir Katastrophen aus der Perspektive der Zukunftsforschung und überprüfen das Vorliegen der Versicherungskriterien. Die Versicherbarkeit ist als problematisch einzustufen. Richtungsweisende privatwirtschaftliche Lösungsansätze sind nicht zu erkennen, sodass eine Substitution durch den Staat eruiert wird.

Wissenschaftliche Validität als Qualitätsmerkmal der Zukunftsforschung

Zukunftsforschung beansprucht, wissenschaftlichen Kriterien zu genügen. Anders als in anderen Disziplinen trifft man jedoch in diesem Fachgebiet auf besondere Herausforderungen hinsichtlich der Kriterien wissenschaftlicher Validität und an die Verfahren ihrer Prüfung, da übliche Ansätze wie die empirische Bewährung oder logische Ableitung in der Zukunftsforschung nicht anwendbar sind. Stattdessen können, so die hier vertretene These, strukturelle Überlegungen aus der Kohärenztheorie der Wahrheit übertragen werden, um die wissenschaftliche Qualität von Zukunftsaussagen konzeptuell zu begreifen und mit Kriterien zur Validierung zu operationalisieren. Entscheidend ist, dass Aussagen der Zukunftsforschung transparent in ihre Bestandteile zerlegt werden und dass sowohl für die Bestandteile als auch für die Art und Weise der Zusammenfügung der Bestandteile belastbare Argumente angeführt werden können. Der Beitrag schließt mit Überlegungen, was von einer explizit wissenschaftlichen Validierung von Zukunftsüberlegungen erwartet werden kann und was nicht.

Acetabulum injuries in infancy and childhood

In this article, the anatomical and morphological features of the acetabulum in infancy and childhood are presented. The pathology and treatment of older children and adolescents is deliberately not covered, because the fracture morphology and treatment of patients aged 13 to 15 years is based on the criteria of adult medicine. Especially in the younger child, the anatomical differences are of particular importance. The younger the child is, the more difficult the diagnosis. Therefore today, MRI examinations should be generous used, even if anesthesia is necessary. If the injured child is hemodynamic stable, anesthesia can be electively used for a more complex diagnosis. Acetabular fractures are particularly problematic in infancy because even with optimal treatment and perfect reduction growth disturbances can occur. These manifest as so-called secondary dysplasia. During treatment, care should be taken to ensure that a surgical team having experience with the infant and juvenile skeleton is available and that appropriate implants are available.

[Mastitis management in Swiss dairy farms with udder health problems]

The objective of this study was to describe the udder health management in Swiss dairy herds with udder health problems. One hundred dairy herds with a yield-corrected somatic cell count of 200'000 to 300'000 cells/ml during 2010 were selected. Data concerning farm structure, housing system, milking technique, milking procedures, dry-cow and mastitis management were collected during farm visits between September and December 2011. In addition, quarter milk samples were collected for bacteriological culturing from cows with a composite somatic cell count ≥ 150'000 cells/ml. The highest quarter level prevalence was 12.3 % for C. bovis. Eighty-two percent of the pipeline milking machines in tie-stalls and 88 % of the milking parlours fulfilled the criteria for the vacuum drop, and only 74 % of the pipeline milking machines met the criteria of the 10-l-water test. Eighty-five percent of the farms changed their milk liners too late. The correct order of teat preparation before cluster attachment was carried out by 37 % of the farmers only. With these results, Swiss dairy farmers and herd health veterinarians can be directed to common mistakes in mastitis management. The data will be used for future information campaigns to improve udder health in Swiss dairy farms.