A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe.

BACKGROUND: To update and compare mortality from primary liver cancer (PLC) and intrahepatic cholangiocarcinoma (ICC) in Europe in 1990-2010. MATERIALS AND METHODS: We used data from the World Health Organization (WHO) to compute age-standardized (world population) mortality rates, and used joinpoint analysis to identify substantial changes. RESULTS: Between 2002 and 2007, PLC rates in the European Union (EU) declined from 3.9 to 3.6/100,000 men. Around 2007, the highest male rates were in France (6.2/100,000), Spain (4.9), and Italy (4.0), while the lowest ones were in Sweden (1.1), the Netherlands (1.2), and the UK (1.8). In women, mortality was lower (0.8/100,000 in 2007 in the EU), and showed more favourable trends, with a decline of over 2% per year over the last two decades as compared with 0.4% in men, in the EU. In contrast, the EU mortality from ICC increased by around 9% in both sexes from 1990 to 2008, reaching rates of 1.1/100,000 men and 0.75/100,000 women. The highest rates were in UK, Germany, and France (1.2-1.5/100,000 men, 0.8-1.1/100,000 women). CONCLUSIONS: PLC mortality has become more uniform across Europe over recent years, with an overall decline; in contrast, ICC mortality has substantially increased in most Europe.

Key electrophysiological, molecular, and metabolic signatures of sleep and wakefulness revealed in primary cortical cultures.

Although sleep is defined as a behavioral state, at the cortical level sleep has local and use-dependent features suggesting that it is a property of neuronal assemblies requiring sleep in function of the activation experienced during prior wakefulness. Here we show that mature cortical cultured neurons display a default state characterized by synchronized burst-pause firing activity reminiscent of sleep. This default sleep-like state can be changed to transient tonic firing reminiscent of wakefulness when cultures are stimulated with a mixture of waking neurotransmitters and spontaneously returns to sleep-like state. In addition to electrophysiological similarities, the transcriptome of stimulated cultures strikingly resembles the cortical transcriptome of sleep-deprived mice, and plastic changes as reflected by AMPA receptors phosphorylation are also similar. We used our in vitro model and sleep-deprived animals to map the metabolic pathways activated by waking. Only a few metabolic pathways were identified, including glycolysis, aminoacid, and lipids. Unexpectedly large increases in lysolipids were found both in vivo after sleep deprivation and in vitro after stimulation, strongly suggesting that sleep might play a major role in reestablishing the neuronal membrane homeostasis. With our in vitro model, the cellular and molecular consequences of sleep and wakefulness can now be investigated in a dish.

High-density collagen gel tubes as a matrix for primary human bladder smooth muscle cells.

Tissue-engineered grafts for the urinary tract are being investigated for the potential treatment of several urologic diseases. These grafts, predominantly tubular-shaped, usually require in vitro culture prior to implantation to allow cell engraftment on initially cell-free scaffolds. We have developed a method to produce tubular-shaped collagen scaffolds based on plastic compression. Our approach produces a ready cell-seeded graft that does not need further in vitro culture prior to implantation. The tubular collagen scaffolds were in particular investigated for their structural, mechanical and biological properties. The resulting construct showed an especially high collagen density, and was characterized by favorable mechanical properties assessed by axial extension and radial dilation. Young modulus in particular was greater than non-compressed collagen tubes. Seeding densities affected proliferation rate of primary human bladder smooth muscle cells. An optimal seeding density of 10(6) cells per construct resulted in a 25-fold increase in Alamar blue-based fluorescence after 2 wk in culture. These high-density collagen gel tubes, ready seeded with smooth muscle cells could be further seeded with urothelial cells, drastically shortening the production time of graft for urinary tract regeneration.

Patient, primary care physician and specialist expectations of primary care physician involvement in cancer care.

BACKGROUND: In Canada, many health authorities recommend that primary care physicians (PCP) stay involved throughout their patients' cancer journey to increase continuity of care. Few studies have focused on patient and physician expectations regarding PCP involvement in cancer care. OBJECTIVE: To compare lung cancer patient, PCP and specialist expectations regarding PCP involvement in coordination of care, emotional support, information transmission and symptom relief at the different phases of cancer. DESIGN: Canadian survey of lung cancer patients, PCPs and cancer specialists PARTICIPANTS: A total of 395 patients completed questionnaires on their expectations regarding their PCP participation in several aspects of care, at different phases of their cancer. Also, 45 specialists and 232 community-based PCP involved in these patients' care responded to a mail survey on the same aspects of cancer care. RESULTS: Most specialists did not expect participation of the PCP in coordination of care in the diagnosis and treatment phases (65% and 78% respectively), in contrast with patients (83% and 85%) and PCPs (80% and 59%) (p < 0.0001). At these same phases, the best agreement among the 3 groups was around PCP role in emotional support: 84% and more of all groups had this expectation. PCP participation in symptom relief was another shared expectation, but more unanimously at the treatment phase (p = 0.85). In the advanced phase, most specialists expect a major role of PCP in all aspects of care (from 81% to 97%). Patients and PCP agree with them mainly for emotional support and information transmission. CONCLUSION: Lung cancer patient, PCP and specialist expectations regarding PCP role differ with the phase of cancer and the specific aspect of cancer care. There is a need to reach a better agreement among them and to better define PCP role, in order to achieve more collaborative and integrated cancer care.

Hyperaldostéronisme primaire sur adénome ou hyperplasie de la surrénale: opérer ou non [Primary hyperaldosteronism with adrenal adenoma or hyperplasia: surgical case or not?].

Primary hyperaldosteronism is one of the most frequent causes of secondary hypertension. Cardiovascular morbimortality is higher than in essential hypertonic and justifies diagnostic and specific treatment of this pathology. Therapeutic choice depends of health and desire of the patient. It is either medical with mineralocorticoid receptor antagonists, or surgical through adrenalectomy. In this case, a pre-surgery exam including a radiologic examination and a venous adrenal catheterism has to be done. Surgery allows a normalisation of kaliema and a blood pressure decrease in 50 to 88% of the patients. Beyond them, 30% are able to stop entirely their medication. Both therapeutic choices decrease cardiovascular risks equally if blood pressure is controlled.

Prescription de statines en prévention primaire: quel score de risque cardiovasculaire faut-il utiliser en Suisse? [Statin prescription in primary prevention: which cardiovascular risk score should be used in Switzerland?]

La prévention primaire des maladies cardiovasculaires par les médecins s'effectue par une prise en charge individualisée des facteurs de risque. L'indication à un traitement par statines se base sur une estimation du risque de survenue d'une maladie cardiovasculaire et sur le taux de LDL-cholestérol. Trois scores de risque sont couramment utilisés: le score PROCAM, le score Framingham, et le SCORE européen. En Suisse, le Groupe Suisse Lipides et Athérosclérose (GSLA) recommande en première instance l'utilisation du score PROCAM avec une adaptation du niveau de risque pour la Suisse. Une enquête a aussi montré que c'est le score le plus utilisé en Suisse. Dans cet article, les particularités de ces scores et leurs applications pratiques en ce qui concerne la prescription de statines en prévention primaire sont discutées. Les conséquences et les bénéfices potentiels de l'application de ces scores en Suisse sont également abordés. [Abstract] Primary prevention of cardiovascular disease by physicians is achieved by management of individual risk factors. The eligibility for treatment with statins is based on both an estimate of the risk of developing cardiovascular disease and the LDL-cholesterol. Three risk scores are commonly used : the PROCAM score, the Framingham score, and the European score. In Switzerland, the Swiss Group Lipids and Atherosclerosis (GSLA) recommends to use the PROCAM score with an adjustment of the level of risk for Switzerland. A survey also showed that PROCAM is the most used in Switzerland. In this article, the differences of these scores and their practical applications regarding the prescription of statins in primary prevention are discussed. The consequences and potential benefits of applying these scores in Switzerland are also discussed.

[Hematological malignancy: management of anemia and leukopenia by primary care physicians]

In hematological malignancies, the occurrence of anemia is very common and can have significant consequences on daily life. Treatment includes essentially red blood cell transfusions. The prescription of erythropoietic agents and/or iron is exceptionnal and often not registered in Switzerland. The onset of neutropenia is also frequently encountered and in some situations may require the prescription of myeloid growth factors. The purpose of this article is to focus on the current recommendations of these two issues for practitioners.

Troubles de la mémoire chez la personne agée: que faire au cabinet [Cognitive impairment in elderly patients: what to do in primary care?].

In Switzerland, each year there are about 25000 new patients suffering from dementia (one new case every 20 minutes!). Currently, recognition of cognitive impairment and dementia diagnoses remain essentially based on clinical features. For the primary care provider, a 4-step approach based on a) history, b) collateral information provided by a knowledgeable relative, c) a standardized brief cognitive screening instrument, and d) simple laboratory tests will identify most older persons suffering from dementia. Unclear situations benefit from an assessment in a memory clinic.

Place de la clinique en médecine ambulatoire--les enseignements de l'etude TOPIC [The place of the clinic in primary case--the TOPIC study].

We know very little about the importance of history and physical examination compared to the importance of paraclinical tests in the diagnostic process in primary care. To answer this question, we examined prospectively 672 consecutive patients with chest pain in primary care. We recorded the timing and the clinical characteristics of the most frequent diagnosis. The resort to laboratory or other clinical tests and reference to specialist were influenced by: emergency consultation, potentially life-threatening aetiology, personal characteristics of the general practitioners' (GP) and patients' anxiety. GPs attributed the diagnosis to history and physical examination alone in 66% and to the association of history, physical examination and tests in 31% cases. This, clinical strategy remains the most important factor in the diagnostic process; even when they are insufficient, they allowed to generate hypotheses and guide investigations.

Lymphome surrénalien primaire bilatéral [Primary bilateral adrenal lymphoma]

When abdominal imaging reveals the existence of unsuspected adrenal masses, a diagnostic strategy is necessary. We report the case of a woman presenting with pulmonary embolism, in whom abdominal ultrasound revealed voluminous masses in both adrenals without clinical or biological signs of hormone hypersecretion, but with mild primary adrenal failure. From a CT scan-directed needle biopsy of the right adrenal mass and subsequent staging we were able to diagnose a primary bilateral adrenal lymphoma, diffuse large B-cell type (REAL/WHO). On CHOP chemotherapy both adrenal masses decreased dramatically and the patient is in remission 18 months later. Primary adrenal lymphoma is a rare condition, since 65 cases have been reported to date. Histological diagnosis is nevertheless important, in view of the excellent response to specific therapy observed in some cases.

Promotion de l'activité physique au cabinet médical: où en sommes- nous en Suisse [Promotion of physical activity in the primary care setting: what is the situation in Switzerland?]

If many harmful effects of a sedentary lifestyle on health are well known, we still need to better understand how effectively promoting regular physical activity in the general population. Among the currently explored strategies, screening for sedentary lifestyle and promoting physical activity in the primary care setting seem promising. Despite recommendations from governmental agencies and professional associations in favor of physical activity counseling, this approach has not been widely adopted so far. This article summarizes the steps taken in Switzerland with an aim of developing physical activity counseling in the primary care setting. It describes how the early implication of primary care physicians influenced in a concrete way the development of a project dedicated to that task.

Primärer Hyperaldosteronismus bei Katzen [Primary hyperaldosteronism in cats].

Primary hyperaldosteronism is a clinical syndrome characterized by an elevated aldosterone secretion by the adrenals. The present case series describes 7 cats with primary hyperaldosteronism, which were presented between 2002 and 2011. Common clinical symptoms were weakness, anorexia, cervical ventroflexion and blindness. All cats showed hypokalemia. In 6 cats, blood pressure was determined: 5 cats showed hypertension, of which 4 animals exhibited retinal detachment and blindness. In the ultrasonographic examination, unilateral adrenomegaly was present in 6 cats whereas one animal showed normal adrenals. In 4 cats, the serum aldosterone concentration was above the reference range. Five cats underwent unilateral adrenalectomy, which was accomplished uneventfully and returned the electrolytes back to normal. Histopathological examination of the adrenals revealed 2 carcinomas and 4 adenomas; one cat with ultrasonographic normal adrenals exhibited bilateral nodular hyperplasia.

Peripheral projections of calretinin-immunoreactive primary sensory neurons in chick hindlimbs.

In chicken dorsal root ganglia, calretinin immunoreactivity is expressed by a subpopulation of large A-neurons, most of which co-express calbindin D-28k. The myelinated axons of these neurons selectively innervate all muscle spindles and most Herbst corpuscles associated to feathers in hindlimbs. It is suggested that the presence of calretinin in primary afferents may be correlated with the electrophysiological properties of rapidly adapting mechanoreceptors.

Cost-effectiveness analysis of a European primary-care physician training in smoking cessation counseling.

BACKGROUND: Physician training in smoking cessation counseling has been shown to be effective as a means to increase quit success. We assessed the cost-effectiveness ratio of a smoking cessation counseling training programme. Its effectiveness was previously demonstrated in a cluster randomized, control trial performed in two Swiss university outpatients clinics, in which residents were randomized to receive training in smoking interventions or a control educational intervention. DESIGN AND METHODS: We used a Markov simulation model for effectiveness analysis. This model incorporates the intervention efficacy, the natural quit rate, and the lifetime probability of relapse after 1-year abstinence. We used previously published results in addition to hospital service and outpatient clinic cost data. The time horizon was 1 year, and we opted for a third-party payer perspective. RESULTS: The incremental cost of the intervention amounted to US$2.58 per consultation by a smoker, translating into a cost per life-year saved of US$25.4 for men and 35.2 for women. One-way sensitivity analyses yielded a range of US$4.0-107.1 in men and US$9.7-148.6 in women. Variations in the quit rate of the control intervention, the length of training effectiveness, and the discount rate yielded moderately large effects on the outcome. Variations in the natural cessation rate, the lifetime probability of relapse, the cost of physician training, the counseling time, the cost per hour of physician time, and the cost of the booklets had little effect on the cost-effectiveness ratio. CONCLUSIONS: Training residents in smoking cessation counseling is a very cost-effective intervention and may be more efficient than currently accepted tobacco control interventions.

Mesenchymal stroma: primary determinant and therapeutic target for epithelial cancer.

Multifocal and recurrent epithelial tumors, originating from either dormant or de novo cancer cells, are major causes of morbidity and mortality. The age-dependent increase of cancer incidence has long been assumed to result from the sequential accumulation of cancer-driving or -facilitating mutations with induction of cellular senescence as a protective mechanism. However, recent evidence suggests that the initiation and development of epithelial cancer results from a close interplay with its altered tissue microenvironment, with chronic inflammation, stromal senescence, autophagy, and the activation of cancer-associated fibroblasts (CAFs) playing possible primary roles. We will discuss recent progress in these areas, and highlight how this understanding may be used for devising novel preventive and therapeutic approaches to the epithelial cancer problem.