Science, practice and patient needs: the work of the Plinius Maior Society.

The Plinius Maior Society is a European multinational, multidisciplinary group of clinicians and researchers in the alcoholism field, which strives for a comprehensive care concept in the management of alcoholism and alcohol-related problems. The Society, using evidence-based medicine, has developed a set of protocols, in the forms of guidelines, flow-charts, leaflets and booklets, for use as tools in research on and treatment of alcohol dependence, with a view to standardize clinical research procedures and to bridge the gap between the alcoholism researcher, practitioner and patient. These protocols or tools have been subjected to a review process during their preparation, and further comments on their validity will be integrated in their updates. Seven protocols have so far been developed, two of which, 'Guidelines on Evaluation of Treatment of Alcohol Dependence' and 'Detection and Management of Patients with Psychiatric and Alcohol Use Disorders', are aimed at the clinical researcher and specialists, whereas three others [in the form of decision trees (flow-charts)] are aimed at the general practitioner and other primary health care providers. These are entitled 'Alcohol Risk Assessment and Intervention in Primary Care', 'Withdrawal from Alcohol at Home' and 'Brief Intervention in Patients with Alcohol-Related Problems'. The remaining two tools are booklets aimed at the patient, one to support initiatives for detection of drinking problems and primary intervention, namely 'Do you have this Problem? Discuss it with your Doctor!', and the other to assist the patient in relapse prevention after the early stages of treatment, namely 'On the Way to Recovery'. The protocols for the general practitioners and patients have so far been produced in seven European languages, and, as with the Guidelines, feedback from target users will be collected and incorporated in future updates. The Society continually seeks to consider areas of clinical importance for its work and, as it enters the new millennium, it hopes to address and make a significant contribution to the most pressing problem in the management of alcohol dependence, namely relapse.

Pour une chirurgie définitive d'emblée dans les ulcères gastro-duodénaux compliqués [Definitive surgery in complicated gastroduodenal ulcers].

Indications for surgical therapy in uncomplicated peptic ulcer disease have decreased considerably since the introduction of H2-receptor blocking drugs and more recently omeprazole. On the other side, the number of acute complications such as perforation or hemorrhage has remained nearly constant. The recent literature seems to indicate that the pattern of patients presenting with complications has changed and that the number of acute ulcers has increased. In a review of 283 patients, we found 150 perforated ulcers (PU) and 133 bleeding ulcers (BU). Almost all the patients with PU and 70% of the patients with BU have been treated operatively. The mortality is 14.3% and 12.5%, respectively. The vast majority of our patients have chronic ulcers, and only 7% have acute or subacute lesions confirmed by histologic examination. Based on our experience and the literature, we propose a therapeutic algorythm for these two conditions.

Les règles n'ont plus la cote: une question de contraception ou de choix [To bleed or not--a new dogma or a real choice in contraception?]

On en parle ! Il est question de la suppression des règles par l'administration de contraceptifs oestro-progestatifs (pilule, patch ou anneau vaginal) en cycles longs (cycles prolongés ; cycles étendus ; extended cycles) entraînant des périodes d'aménorrhée, rythmées par des intervalles libres de sept jours sans administration hormonale. L'indication à ce mode de prescription est presque unanimement reconnue pour le traitement des pathologies bénéficiant de la suppression des règles et des fluctuations hormonales inhérentes à l'activité ovarienne. Ce traitement suscite cependant également de l'intérêt pour une indication du type mode de vie. Les modalités thérapeutiques, les avantages et inconvénients sont examinés à la lumière de l'attente des femmes et de leur droit au choix éclairé et libre. Let's talk about it ! Suppression of menstruation, by extending the duration of contraceptives containing estro-progestins (oral contraception, patch or vaginal ring) to long cycles, is a new approach in the field of contraception. These extended cycles aim at obtaining prolonged amenorrhea, interrupted periodically by a free interval of 7 days without hormone intake and thus causing breakthrough bleeding. Pathologies, which are supposed to get some benefit from the suppression of menstruation and of hormone level variations related to ovarian activity, are widely recognized as an indication. Some interest is also coming up for so called life style indications. Treatment issues, advantages and disadvantages are examined in the light of women's expectations and right to access to informed consent and independent choice.

Acute intussusception: a classic clinical picture?

57 patients with acute intussusception were admitted to the Children's Hospital Zurich between 1972 and 1979. All were treated surgically. One died, 7 needed a bowel resection, 9 intussusceptions were difficult and 32 easy to reduce. The retrospectively reviewed data show that the classic symptomatology, beginning suddenly in a healthy male (60%) under 3 years of age (91%) with attacks of colicky pain (81%), vomiting (93%), a palpable abdominal mass (72%) and rectal bleeding (72%), appears during the course of illness or may not be present at all. This leads to misdiagnosis, wrong treatment and worsening of the pathology. Blood per rectum, the most typical symptom, was present in the first hours of illness in only 5%, vomiting in 44% and colicky pain in 33% of the patients. A high degree of awareness is therefore necessary to diagnose intussusception during the first hours of illness, and particular stress must be laid on the accuracy of the diagnosis because reducibility and resection rate depend directly on the duration of the symptoms.

Identifying psychotic defenses in a clinical interview.

The Defense Mechanisms Rating Scales (DMRS), one of the most widely used and validated instruments in the study of defense mechanisms, does not include psychotic defenses. The Psychotic-DMRS (P-DMRS) has been developed to include 6 psychotic defense mechanisms: psychotic denial, autistic withdrawal, distortion, delusional projection, fragmentation, and concretization. We discuss psychotic defenses, including the difference between psychotic defenses and psychotic symptoms. Six clinical illustrations demonstrate how the 6 P-DMRS defenses can be identified in patients' narratives selected from the transcripts of dynamic interviews. Implications with respect to patient evaluation and treatment are discussed.

Recovery of postoperative visual loss following treatment of severe anaemia.

A 29-year-old pregnant woman noted acute visual loss following emergent Caesarean section complicated by excessive uterine bleeding. Postoperative visual acuity was count fingers in both eyes. Funduscopic changes were consistent with a diagnosis of anaemia-associated ischaemic optic neuropathy and retinopathy. One month later, because of persistent anaemia and poor visual recovery, blood transfusion was given. Following transfusion, the patient's vision improved over the next 6 months. In an otherwise healthy patient, visual loss associated with postoperative blood loss may still be partially reversible with correction of the anaemia, even after a delayed period of time.

Oral and intravenous methadone use: some clinical and pharmacokinetic aspects.

A sample of 15 patients participating in an injectable methadone trial and of 15 patients in an oral methadone maintenance treatment, who admitted injecting part or all of their methadone take-home doses, were compared to 20 patients in maintenance treatment who use methadone exclusively by mouth. The present study confirms the poorer general health, the higher levels of emotional, psychological or psychiatric problems, the higher use of illicit drugs, and the higher number of problems related to employment and support associated with the use of the intravenous mode of administration of methadone. As expected, due to the shunt of metabolism in the gut wall and of the liver first-pass effect, higher concentration to dose ratios of (R)-methadone, which is the active enantiomer, were measured in the intravenous group (23% increase). This difference reached an almost statistically significant value (P = 0.054). This raises the question whether the effect of a higher methadone dose could be unconsciously sought by some of the intravenous methadone users.

Le sevrage ultra-rapide sous anesthésie générale: l'expérience de l'Hôpital de St-Loup [Ultrafast opiate detoxification under general anesthesia: the St. Loup Hospital experience]

Rapid antagonist induction under anesthesia is a method that has been increasingly used to detoxify opiate addicts. These procedures are useful to reduce the duration and the discomfort of withdrawal. However, the high risk and the cost of these methods require randomized clinical trial to evaluate safety and clinical effectiveness. The University Substance Abuse Division of Lausanne and the Intensive Care Unit of the St-Loup Hospital work on a randomized clinical trial comparing anesthesia-assisted versus traditional clonidine detoxification combined with an additional psychosocial week. This paper describes the technique of anesthesia used in our study. Our clinical experience suggests that, integrating this technique in a multidisciplinary network, with a strong emphasis on post-anesthetic follow-up, is a viable and safe option in the treatment of opiate dependence.

Managing the crises : How do Swiss municipalities react to the crisis and what explains the differences ?

Swiss municipalities are to an import ant extent responsible for their own resources. Since these resources primarily depend on income and property tax from individuals and enterprises, their budgets are likely to be directly affected by the actual crisis of the financial sector and the economy. This paper investigates how the municipalities perceive this threat and how they reacted to it or plan to do so. In a nationwide survey conducted at the end of 2009 in all 2596 Swiss municipalities, we asked the local secretaries which measures they launch in order to cope with expected losses in tax income and a possible increase of welfare spending. Do the municipalities rather rely on Keynesian measures increasing public spending and accepting greater deficits, or do they try to avoid further deficits by austerity measures and a withdrawal of planned investments? The paper shows that only a few municipalities - mainly the bigger ones - expect to be strongly hit by the crisis. Their reactions, however, do not reveal the clear patterns theory lets to expect. Preferences for austerity measures and deficit spending become visible but many municipalities take measures from both theories. The strongest explaining factor whether municipalities react is the affectedness by the crisis followed by the fact that the municipality belongs to the French speaking part of the country. Size also has an effect whereas the strength of the Social Democrats is negligible. More difficult is it, to explain what kind of measures municipalities are likely to take.

Risk of falls and major bleeds in patients on oral anticoagulation therapy.

BACKGROUND: The risk of falls is the most commonly cited reason for not providing oral anticoagulation, although the risk of bleeding associated with falls on oral anticoagulants is still debated. We aimed to evaluate whether patients on oral anticoagulation with high falls risk have an increased risk of major bleeding. METHODS: We prospectively studied consecutive adult medical patients who were discharged on oral anticoagulants. The outcome was the time to a first major bleed within a 12-month follow-up period adjusted for age, sex, alcohol abuse, number of drugs, concomitant treatment with antiplatelet agents, and history of stroke or transient ischemic attack. RESULTS: Among the 515 enrolled patients, 35 patients had a first major bleed during follow-up (incidence rate: 7.5 per 100 patient-years). Overall, 308 patients (59.8%) were at high risk of falls, and these patients had a nonsignificantly higher crude incidence rate of major bleeding than patients at low risk of falls (8.0 vs 6.8 per 100 patient-years, P=.64). In multivariate analysis, a high falls risk was not statistically significantly associated with the risk of a major bleed (hazard ratio 1.09; 95% confidence interval, 0.54-2.21). Overall, only 3 major bleeds occurred directly after a fall (incidence rate: 0.6 per 100 patient-years). CONCLUSIONS: In this prospective cohort, patients on oral anticoagulants at high risk of falls did not have a significantly increased risk of major bleeds. These findings suggest that being at risk of falls is not a valid reason to avoid oral anticoagulants in medical patients.

Clinical characteristics and outcome of inpatients versus outpatients with venous thromboembolism: findings from the RIETE Registry.

BACKGROUND: Patients with venous thromboembolism (VTE) treated with anticoagulants are at risk of death from pulmonary embolism (PE) and/or bleeding. However, whether patients who develop VTE in hospital have a higher complication rate than those who develop VTE in an outpatient setting is unclear. PATIENTS AND METHODS: RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We compared the 3-month incidence of fatal PE and fatal bleeding in patients in whom the VTE had developed while in hospital for another medical condition (inpatients) with those who presented to the emergency ward because of VTE (outpatients). RESULTS: Up to April 2008, 22,133 patients with acute VTE were enrolled: 10,461 (47%) presented with PE, 11,672 with deep vein thrombosis. Overall, 6445 (29%) were inpatients. During the study period, those who developed VTE as inpatients had a significantly higher incidence of fatal PE (2.1% vs. 1.5%; odds ratio: 1.4; 95% CI: 1.1-1.7), overall death (7.0% vs. 5.4%; odds ratio: 1.3; 95% CI: 1.2-1.5), and major bleeding (2.9% vs. 2.1%; odds ratio: 1.4; 95% CI: 1.1-1.6) than outpatients. The incidence of fatal bleeding was not significantly increased (0.7% vs. 0.5%; odds ratio: 1.2; 95% CI: 0.9-1.8). In multivariable analysis, inpatient status was significantly associated with a higher risk for fatal PE (odds ratio: 1.3; 95% CI: 1.1-1.7). CONCLUSIONS: VTE occurring in hospitalized patients carries a significantly higher risk for death of PE than in outpatients, underscoring the importance of VTE prevention strategies in the hospital setting.

Home versus in-hospital treatment of outpatients with acute deep venous thrombosis of the lower limbs.

BACKGROUND: Some physicians are still concerned about the safety of treatment at home of patients with acute deep venous thrombosis (DVT). METHODS: We used data from the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry to compare the outcomes in consecutive outpatients with acute lower limb DVT according to initial treatment at home or in the hospital. A propensity score-matching analysis was carried out with a logistic regression model. RESULTS: As of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were treated at home. Patients treated at home were more likely to be male and younger and to weigh more; they were less likely than those treated in the hospital to have chronic heart failure, lung disease, renal insufficiency, anemia, recent bleeding, immobilization, or cancer. During the first week of anticoagulation, 27 patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and 51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled, and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis, patients treated at home had a similar rate of venous thromboembolism recurrences and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1-1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the first week compared with those treated in the hospital. CONCLUSIONS: In outpatients with DVT, home treatment was associated with a better outcome than treatment in the hospital. These data may help safely treat more DVT patients at home.

16-OR: Investigation of Sharp Trauma and Gunshot Cases Using Post-mortem CT-Angiography

Investigation of violent death, especially cases of sharp trauma and gunshot, is an important part of medico-legal investigations. Beside the execution of a conventional autopsy, the performance of a post-mortem Multi-Detector Computed Tomography (MDCT)-scan has become a highly appreciated tool. In order to investigate also the vascular system, post-mortem CT-angiography has been introduced. The most studied and widespread technique is the Multi-phase post-mortem CT-angiography (MPMCTA). Its sensitivity to detect vascular lesions is even superior to conventional autopsy. The application of MPMCTA for cases of gunshot and sharp-trauma is therefore an obvious choice, as vascular lesions are common in such victims. In most cases of sharp trauma and in several cases of gunshots, death can be attributed to exsanguinations. MPMCTA is able to detect the exact source of bleeding and also to visualize trajectories, which are of most importance in these cases. The reconstructed images allow to clearly visualizing the trajectory in a way that is easily comprehensible for not medically trained legal professionals. The sensitivity of MPMCTA for soft tissue and organ lesions approximately matches the sensitivity of conventional autopsy. However, special care, experience and effective use of the imaging software is necessary for performing the reconstructions of the trajectory. Large volume consuming haemorrhages and shift of inner organs are sources of errors and misinterpretations. This presentation shall give an overview about the advantages and limitations of the use of MPMCTA for investigating cases of gunshot and sharp-trauma.

Insight in protein S deficiency from mouse models

Protein S (ProS) is an important negative regulator of blood coagulation. Its physiological importance is evident in purpura fulminans and other life-threatening thrombotic disorders typical of ProS deficient patients. Our previous characterization of ProS deficiency in mouse models has shown similarities with the human phenotypes: heterozygous ProS-deficient mice (Pros+/-) had increased thrombotic risk whereas homozygous deficiency in ProS (Pros-/-) was incompatible with life (Blood 2009; 114:2307-2314). In tissues, ProS exerts cellular functions by binding to and activating tyrosine kinase receptors of the Tyro3 family (TAM) on the cell surface.To extend the analysis of coagulation defects beyond the Pros-/- phenotype and add new insights into the sites of synthesis ProS and its action, we generated mice with inactivated ProS in hepatocytes (Proslox/loxAlbCre+) as well as in endothelial and hematopoietic cells (Proslox/loxTie2Cre+). Both models resulted in significant reduction of circulating ProS levels and in a remarkable increased thrombotic risk in vivo. In a model of tissue factor (TF)-induced venous thromboembolism (VTE), only 17% of Proslox/loxAlbCre+ mice (n=12) and only 13% of Proslox/loxTie2Cre+ mice (n=14) survived, compared with 86% of Proslox/lox mice (n=14; P<0.001).To mimic a severe acquired ProS deficiency, ProS gene was inactivated at the adult stage using the polyI:C-inducible Mx1-Cre system (Proslox/loxMx1Cre+). Ten days after polyI:C treatment, Proslox/loxMx1Cre+ mice developed disseminated intravascular coagulation with extensive lung and liver thrombosis.It is worth noting that no skin lesions compatible with purpura fulminans were observed in any of the above-described models of partial ProS deficiency. In order to shed light on the pathogenesis of purpura fulminans, we exposed the different ProS-deficient mice to warfarin (0.2 mg/day). We observed that Pros+/-, Proslox/loxAlbCre+ and Proslox/loxTie2Cre+ mice developed retiform purpura (characterized by erythematous and necrotic lesions of the genital region and extremities) and died after 3 to 5 days after the first warfarin administration.In human, ProS is also synthesized by megakaryocytes and hence stored at high concentrations in circulating platelets (pProS). The role of pProS has been investigated by generating megakaryocyte ProS-deficient model using the PF4 promoter as Cre driver (Proslox/loxPf4Cre+). In the TF-induced VTE model, Proslox/loxPf4Cre+ (n=15) mice showed a significant increased risk of thrombosis compared to Proslox/lox controls (n=14; survival rate 47% and 86%, respectively; P<0.05). Furthermore, preliminary results suggest survival to be associated with higher circulating ProS levels. In order to evaluate the potential role of pProS in thrombus formation, we investigated the thrombotic response to intravenous injection of collagen-epinephrine in vivo and platelet function in vitro. Both in vivo and in vitro experiments showed similar results between Proslox/loxPf4Cre+ and Proslox/lox, indicating that platelet reactivity was not influenced by the absence of pProS. These data suggest that pProS is delivered at the site of thrombosis to inhibit thrombin generation.We further investigated the ability of ProS to function as a ligand of TAM receptors, by using homozygous and heterozygous deficient mice for both the TAM ligands ProS and Gas6. Gas6-/-Pros-/- mice died in utero and showed comparable dramatic bleeding and thrombotic phenotype as described for Pros-/- embryos.In conclusion, like complete ProS deficiency, double deficiency in ProS and Gas6 was lethal, whereas partial ProS deficiency was not. Mice partially deficient in ProS displayed a prothrombotic phenotype, including those with only deficiency in pProS. Purpura fulminans did not occur spontaneously in mice with partial Pros deficiency but developed upon warfarin administration.Thus, the use of different mice models of ProS deficiency can be instrumental in the study of its highly variable thrombotic phenotype and in the investigation of additional roles of ProS in inflammation and autoimmunity through TAM signaling.

Predictors of the Indefinite Duration Anticoagulation Treatment Strategy In Patients with Cancer Associated Thrombosis

Background: In patients with cancer and acute venous thromboembolism (VTE), current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved.Methods and results: Among 1'247 patients with acute VTE enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER) from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, and 83 (26%) tumor surgery within 6 months. Patients with cancer were older (66±14 vs. 60±19 years, p<0.001), more often hospitalized at the time of VTE diagnosis (46% vs. 36%, p=0.001), immobile for >3 days (25% vs. 16%, p<0.001), and more often had thrombocytopenia (6% vs. 1%, p<0.001) than patients without cancer. The 30-day rate of VTE-related death or recurrent VTE was 9% in cancer patients vs. 4% in patients without cancer (p<0.001), and the rates of bleeding requiring medical attention were 5% in both groups (p=0.57). Cancer patients received indefinite-duration anticoagulation treatment more often than patients without cancer (47% vs. 19%, p<0.001), and LMWH mono-therapy during the initial 3 months was prescribed to 45% vs. 8%, p<0.001, respectively. Among patients with cancer, prior VTE (OR 4.0, 95%CI 2.0-8.0), metastatic disease (OR 3.0, 95%CI 1.7-5.2), outpatient status at the time of VTE diagnosis (OR 3.8, 95%CI 1.9-7.6), and inpatient treatment (OR 4.4, 95%CI 2.1-9.2) were independently associated with the prescription of indefinite-duration anticoagulation treatment.Conclusions: Less than half of the cancer patients with acute VTE received a prescription for indefinite-duration anticoagulation treatment. Recurrent VTE, metastatic cancer, outpatient VTE diagnosis, and VTE requiring hospitalization were associated with an increased use of this strategy.