The role of postoperative prophylactic antibiotics in the treatment of facial fractures: a randomised, double-blind, placebo-controlled pilot clinical study. Part 3: Le Fort and zygomatic fractures in 94 patients

The aim of this study was to evaluate the difference between the effect of a 5-day and a 1-day postoperative course of antibiotics on the incidence of infection after midfacial fractures. A total of 98 patients with displaced Le Fort or zygomatic fractures that required operation were randomly assigned into 2 groups, both of which were given amoxicillin/clavulanic acid 1.2g intravenously every 8h from the time of admission until 24h postoperatively. The 5-day group was then given amoxicillin/clavulanic acid 625mg orally 8-hourly for another 4 days. The 1-day group was given placebo orally at the same time points. Patients were followed up 1, 2, 4, 6, and 12 weeks, and 6 months, postoperatively. The development of an infection of the wound was the primary end point. Ninety-four of the 98 patients completed the study. Two of the 45 patients in the 5-day group (4%) and 2/49 in the 1-day group (4%) developed postoperative wound infections. One in each group had a purulent infection, while the others had only wound breakdown. Two patients of the 5-day group and one in the 1-day group developed rashes on the trunk. There were no significant differences in the incidence of infection or side effects between the groups. In midfacial fractures a 1-day course of antibiotics postoperatively is as effective in preventing infective complications as a 5-day regimen.

Cytomegalovirus Serology and Replication Remain Associated With Solid Organ Graft Rejection and Graft Loss in the Era of Prophylactic Treatment

BACKGROUND Cytomegalovirus (CMV) replication has been associated with more risk for solid organ graft rejection. We wondered whether this association still holds when patients at risk receive prophylactic treatment for CMV. METHODS We correlated CMV infection, biopsy-proven graft rejection, and graft loss in 1,414 patients receiving heart (n=97), kidney (n=917), liver (n=237), or lung (n=163) allografts reported to the Swiss Transplant Cohort Study. RESULTS Recipients of all organs were at an increased risk for biopsy-proven graft rejection within 4 weeks after detection of CMV replication (hazard ratio [HR] after heart transplantation, 2.60; 95% confidence interval [CI], 1.34-4.94, P<0.001; HR after kidney transplantation, 1.58; 95% CI, 1.16-2.16, P=0.02; HR after liver transplantation, 2.21; 95% CI, 1.53-3.17, P<0.001; HR after lung transplantation, 5.83; 95% CI, 3.12-10.9, P<0.001. Relative hazards were comparable in patients with asymptomatic or symptomatic CMV infection. The CMV donor or recipient serological constellation also predicted the incidence of graft rejection after liver and lung transplantation, with significantly higher rates of rejection in transplants in which donor or recipient were CMV seropositive (non-D-/R-), compared with D- transplant or R- transplant (HR, 3.05; P=0.002 for liver and HR, 2.42; P=0.01 for lung transplants). Finally, graft loss occurred more frequently in non-D- or non-R- compared with D- transplant or R- transplant in all organs analyzed. Valganciclovir prophylactic treatment seemed to delay, but not prevent, graft loss in non-D- or non-R- transplants. CONCLUSION Cytomegalovirus replication and donor or recipient seroconstellation remains associated with graft rejection and graft loss in the era of prophylactic CMV treatment.

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis

OBJECTIVES Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. METHODS We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. RESULTS Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. CONCLUSIONS Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.

Prophylactic use of bevacizumab to avoid anterior segment neovascularization following proton therapy for uveal melanoma.

PURPOSE To investigate whether the prophylactic use of bevacizumab reduces the rate of rubeosis after proton therapy for uveal melanoma and improves the possibility to treat ischemic, reapplicated retina with laser photocoagulation. DESIGN Comparative retrospective case series. METHODS Uveal melanoma patients with ischemic retinal detachment and treated with proton therapy were included in this institutional study. Twenty-four eyes received prophylactic intravitreal bevacizumab injections and were compared with a control group of 44 eyes without bevacizumab treatment. Bevacizumab injections were performed at the time of tantalum clip insertion and were repeated every 2 months during 6 months, and every 3 months thereafter. Ultra-widefield angiography allowed determination of the extent of retinal ischemia, which was treated with laser photocoagulation after retinal reapplication. Main outcome measures were the time to rubeosis, the time to retinal reattachment, and the time to laser photocoagulation of ischemic retina. RESULTS Baseline characteristics were balanced between the groups, except for thicker tumors and larger retinal detachments in the bevacizumab group, potentially to the disadvantage of the study group. Nevertheless, bevacizumab prophylaxis significantly reduced the rate of iris rubeosis from 36% to 4% (log-rank test P = .02) and tended to shorten the time to retinal reapplication until laser photocoagulation of the nonperfusion areas could be performed. CONCLUSIONS Prophylactic intravitreal bevacizumab in patients treated with proton therapy for uveal melanoma with ischemic retinal detachment prevented anterior segment neovascularization, until laser photocoagulation to the reapplied retina could be performed.

Prophylactic antibiotics or G(M)-CSF for the prevention of infections and improvement of survival in cancer patients receiving myelotoxic chemotherapy.

BACKGROUND Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (macrophage) colony-stimulating factors (G(M)-CSF) and antibiotics, frequently quinolones or cotrimoxazole. Current guidelines recommend the use of colony-stimulating factors when the risk of febrile neutropenia is above 20%, but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken. OBJECTIVES To compare the efficacy and safety of G(M)-CSF compared to antibiotics in cancer patients receiving myelotoxic chemotherapy. SEARCH METHODS We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to December 2015). We planned to include both full-text and abstract publications. Two review authors independently screened search results. SELECTION CRITERIA We included randomised controlled trials (RCTs) comparing prophylaxis with G(M)-CSF versus antibiotics for the prevention of infection in cancer patients of all ages receiving chemotherapy. All study arms had to receive identical chemotherapy regimes and other supportive care. We included full-text, abstracts, and unpublished data if sufficient information on study design, participant characteristics, interventions and outcomes was available. We excluded cross-over trials, quasi-randomised trials and post-hoc retrospective trials. DATA COLLECTION AND ANALYSIS Two review authors independently screened the results of the search strategies, extracted data, assessed risk of bias, and analysed data according to standard Cochrane methods. We did final interpretation together with an experienced clinician. MAIN RESULTS In this updated review, we included no new randomised controlled trials. We included two trials in the review, one with 40 breast cancer patients receiving high-dose chemotherapy and G-CSF compared to antibiotics, a second one evaluating 155 patients with small-cell lung cancer receiving GM-CSF or antibiotics.We judge the overall risk of bias as high in the G-CSF trial, as neither patients nor physicians were blinded and not all included patients were analysed as randomised (7 out of 40 patients). We considered the overall risk of bias in the GM-CSF to be moderate, because of the risk of performance bias (neither patients nor personnel were blinded), but low risk of selection and attrition bias.For the trial comparing G-CSF to antibiotics, all cause mortality was not reported. There was no evidence of a difference for infection-related mortality, with zero events in each arm. Microbiologically or clinically documented infections, severe infections, quality of life, and adverse events were not reported. There was no evidence of a difference in frequency of febrile neutropenia (risk ratio (RR) 1.22; 95% confidence interval (CI) 0.53 to 2.84). The quality of the evidence for the two reported outcomes, infection-related mortality and frequency of febrile neutropenia, was very low, due to the low number of patients evaluated (high imprecision) and the high risk of bias.There was no evidence of a difference in terms of median survival time in the trial comparing GM-CSF and antibiotics. Two-year survival times were 6% (0 to 12%) in both arms (high imprecision, low quality of evidence). There were four toxic deaths in the GM-CSF arm and three in the antibiotics arm (3.8%), without evidence of a difference (RR 1.32; 95% CI 0.30 to 5.69; P = 0.71; low quality of evidence). There were 28% grade III or IV infections in the GM-CSF arm and 18% in the antibiotics arm, without any evidence of a difference (RR 1.55; 95% CI 0.86 to 2.80; P = 0.15, low quality of evidence). There were 5 episodes out of 360 cycles of grade IV infections in the GM-CSF arm and 3 episodes out of 334 cycles in the cotrimoxazole arm (0.8%), with no evidence of a difference (RR 1.55; 95% CI 0.37 to 6.42; P = 0.55; low quality of evidence). There was no significant difference between the two arms for non-haematological toxicities like diarrhoea, stomatitis, infections, neurologic, respiratory, or cardiac adverse events. Grade III and IV thrombopenia occurred significantly more frequently in the GM-CSF arm (60.8%) compared to the antibiotics arm (28.9%); (RR 2.10; 95% CI 1.41 to 3.12; P = 0.0002; low quality of evidence). Neither infection-related mortality, incidence of febrile neutropenia, nor quality of life were reported in this trial. AUTHORS' CONCLUSIONS As we only found two small trials with 195 patients altogether, no conclusion for clinical practice is possible. More trials are necessary to assess the benefits and harms of G(M)-CSF compared to antibiotics for infection prevention in cancer patients receiving chemotherapy.

Total Thyroidectomy for Amiodarone-induced Thyrotoxicosis in the Hyperthyroid State.

Amiodarone is a potent antiarrhythmic agent, indicated for the treatment of refractory arrhythmias, which may lead to thyrotoxicosis. In these patients, thyroidectomy is a valid therapeutic option. Antithyroid therapy in the immediate preoperative setting and the subsequently accepted minimal delay until thyroidectomy have not been clearly defined yet. The aim of the present study was to show, that total thyroidectomy under general anaesthesia in patients with amiodarone-induced thyrotoxicosis (AIT) is safe without necessarily obtaining an euthyroid state preoperatively.We conducted a retrospective cohort study of prospectively gathered data on 11 patients undergoing total thyroidectomy under general anaesthesia between January 2008 and December 2013 for AIT at our University Hospital.All patients were preoperatively treated with carbimazole, steroids and β-receptor antagonists. Additionally, 3 patients received potassium perchlorate and in one patient carbimazole was changed to propylthiouracil. Plasmapheresis was performed in 3 patients. Only one patient was euthyroid at the time of operation. There were no significant intra- and postoperative complications, especially no signs of thyroid storm. One patient could postoperatively be removed from the cardiac transplant waiting list due to improved cardiac function.Improvements in the interdisciplinary surgical management for AIT between cardiologists, endocrinologists, anaesthetists and endocrine surgeons provide the basis of safe total thyroidectomy under general anaesthesia in hyperthyroid state. Early surgery without long delay for medical antithyroid treatment (with its potential negative side effects) is recommended.

Medicinal plants - prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review.

BACKGROUND Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves ≤ 35 %; piglets ≤ 50 %) and for respiratory diseases (calves ≤ 80 %; piglets ≤ 40 %). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as 'multi-target drugs'. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets. RESULTS Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20'000 peer-reviewed articles published in the last 20 years (1994-2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation. CONCLUSIONS Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies.

Permanent teeth with horizontal root fractures after dental trauma. A retrospective study

The purpose of the present retrospective study was to evaluate the post-traumatic healing of the pulp and periodontium of 32 permanent teeth with horizontal root fractures. Twenty-nine patients, 8-48 years old, who presented at our department with a root fracture between January 2001 and April 2007, participated in the study. Root-fractured teeth with a loosened or dislocated coronal fragment were repositioned and splinted for 14-49 days (average: 34 days). In cases of severe dislocation of the coronal fragment, prophylactic endodontic treatment was performed. Follow-up examinations were conducted routinely after 1,2,3,6, and 12 months. For this study, follow-up took place for up to 7 years post trauma. Of 32 root-fractured teeth, 29 (91%) survived. 10 teeth (31%) exhibited pulpal healing; 13 teeth (41%) were prophylactically endodontically treated within 2 weeks of injury. At the fracture line, interposition of calcified tissue was evident in 6 teeth (19%), and interposition of granulation tissue was observed in 8 teeth (25%). The prognosis of the root-fractured teeth was good, and one-third of the teeth with root fractures possessed a vital pulp at the final examination.

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem.

Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.

Immunohistochemical localization of osteoclastogenic cell mediators in feline tooth resorption and healthy teeth

Tooth resorption is among the most common and most challenging problems in feline dentistry It is a progressive disease eventually leading to tooth loss and often root replacement. The etiology of moth resorption remains obscure and to date no effective therapeutic approach is known. The present study is aimed at assessing the reliability of radiographic imaging and addressing the possible involvement of receptor activator of NF kappa B (RANK), its ligand (RANKL), and osteoprotegerin (OPG) in the process of tooth resorption. Teeth from 8 cats were investigated by means of radiographs and paraffin sections followed by immunolabeling. Six cats were diagnosed with tooth resorption based on histopathologic and radiographic findings. Samples were classified according to a four-stage diagnostic system. Radiologic assessment of tooth resorption correlated very strongly with histopathologic findings. Tooth resorption was accompanied by a strong staining with all three antibodies used, especially with anti-RANK and anti-RANKL antibodies. The presence of OPG and RANKL at the resorption site is indicative of repair attempts by fibroblasts and stromal cells. These findings should be extended by further investigations in order to elucidate the pathophysiologic processes underlying tooth resorption that might lead to prophylactic and/or therapeutic measures. J Vet Dent 27(2); 75 - 83, 2010

Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10

Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609?620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.

A nation-wide initiative against venous thromboembolism

There is a gap between knowledge and recommendations regarding venous thromboembolism (VTE) on the one hand and daily practice on the other. This fact has prompted a Swiss multidisciplinary group consisting of angiologists, haematologists, internists, and emergency medicine and pharmaceutical medicine specialists interested in VTE, the SAMEX group, to set up a series of surveys and studies that give useful insight into the situation in our country. Their projects encompassed prophylactic and therapeutic aspects of VTE, and enrolled over 7000 patients from five academic and 45 non-academic acute care hospitals and fifty-three private practices in Switzerland. This comprehensive Swiss Clinical Study Programme forms the largest database surveying current clinical patterns of VTE management in a representative sample of the Swiss patient population. Overall the programme shows a lack of thromboprophylaxis use in hospitalised at-risk medical patients, particularly in those with cancer, acute heart or respiratory failure and the elderly, as well as under-prescription of extended prophylaxis beyond hospital discharge in patients undergoing major cancer surgery. In regard to VTE treatment, planning of anticoagulation duration, administration of LMWH for cancer-associated thrombosis, and the use of compression therapy for prevention of post-thrombotic syndrome in patients with symptomatic proximal DVT require improvement. In conclusion, this programme highlights insufficient awareness of venous thromboembolic disease in Switzerland, underestimation of its burden and inconsistent application of international consensus statement guidelines regarding prophylaxis and treatment adopted by the Swiss Expert Group.

[Driving ability and daytime sleepiness]

Daytime sleepiness is a complaint of about 5-10% in a normal population. The consequences, such as impaired performance and accidents at the workplace and while driving, have major impact on the affected and on society. According to Swiss federal statistics only 1-3% of all motor vehicle accidents are due to excessive daytime sleepiness, which is in great contrast to a figure of 10 to 20% of all accidents derived from scientific studies. Due to the inadequate statistical representation of the problem, insufficient countermeasures have been realized, and the state of drivers breaching traffic regulations is not adequately investigated in this respect. The most prevalent cause of microsleep induced accidents is certainly lack of sleep due to social or professional reasons. A treating physician must also consider sedating drugs and various diseases. The typical characteristics of accidents due to falling asleep at the wheel and the risk factors involved are well established, so that informing the general public, taking prophylactic countermeasures and a targeted investigation in this respect of drivers who have breached the law are all feasible. Since symptoms of sleepiness can be recognized well before any impairment of performance occurs, the most important countermeasure is information of the drivers on the risk factors and on efficient countermeasures against sleepiness at the wheel. Besides correct diagnosis and treatment, the primary goal of physicians treating patients with pathological daytime sleepiness is to inform them at an early stage about the risks of sleepiness and the large responsibility they bear while driving. This information should be written down in the patients' records. Professional drivers suffering from daytime sleepiness, drivers who have already had an accident due to microsleep and unreasonable drivers should be referred to a centre of sleep disorders for objective measurements of sleepiness.