[Budget impact of self-testing in the national cervical cancer screening program]. / Impact budgétaire de l'utilisation de l'autotest dans le cadre du programme national de dépistage du cancer du col de l'utérus.

OBJECTIVES: A nationwide screening program for cervical cancer (CC) was organized in 2018 as part of the 2014-2019 French cancer plan, with the objective of reducing CC incidence and mortality in France by reaching an 80 % coverage rate. As an alternative to pap smear, vaginal self-sampling (VSS) aimed at identifying high-risk HPV carriage could help to achieve this goal. The objective of the present study is to compare the respective budgetary impacts of several self-sampling strategies. METHOD: A budget impact model was developed to compare non-use of self-sampling in CC screening to the 5-year costs of 5 VSS strategies viewed from an all-payer perspective. While the first strategy was based on mailing the VSS kit with a reminder to participate in the screening program, the second was based on accompanying the mailed kit with an invitation to participate. The third and fourth strategies were based on providing health professionals with the kit, and thereby offering self-sampling as an alternative to pap smears for women undergoing CC screening and having previously received the kits. Finally, the fifth strategy was based on self-sampling as the one and only CC screening modality. The parameters of the model were based on past screening participation data and experiments in France on organized screening and VSS use. The costs included those of procedures associated with screening and program organization. RESULTS: All in all, the costs associated with cervical cancer screening would represent approximately 1 billion euros over 5 years. All strategies would be associated with participation ranging from 81% to 84%, which would represent an increase of 4.7% to 5.2% of lesions diagnosed by screening and a cost reduction between €30M and €87M over 5 years, with the exception of the strategy based on sending the kit (with the reminder associated or not) to the health professionals offering this option (+€23M and +€6M). CONCLUSIONS: In conclusion, the use of self-sampling as an alternative to pap smears for non-participating women would increase participation, with only a moderate budgetary impact and could, in some cases, even induce savings.

[Estimated impact of the current colorectal screening program in France]. / Estimation de l'impact du programme actuel de dépistage organisé du cancer colorectal.

BACKGROUND: Colorectal cancer is the third most common cancer and the second most deadly in France. A Cochrane meta-analysis has confirmed the benefits of colorectal cancer screening. A nationwide colorectal screening program was set up in France in 2009 for medium-risk, asymptomatic people aged 50 to 74 years. It has been based, since 2015, on the Fecal Immunochemical Test. The participation rate for 2016-2017 was 34%, which is lower than the European objectives. The objective of this study was to evaluate the impact of the program at the current participation rate and at rates of 45% and 65%. METHODS: The epidemiological impact of the program was estimated from the results of an individual simulation model adapted from the Microsimulation Screening Analysis Colon model, calibrated and transposed to the French context. An initial analysis was conducted to estimate the individual impact of screening and a second for the entire eligible population, at various participation rates. RESULTS: The test is associated with a lifetime reduction in the risk of colorectal cancer of 24% for men and 21% for women, and a reduction in the risk of death from colorectal cancer of 51% and 43% respectively. At the current level of participation, the program reduces incidence by 5% and mortality by 14% compared to no organized screening. The impact would be reduced by an additional 3% and 8% for participation rates of 45% and 65% respectively. Similarly, mortality would decrease by an additional 8% and 22%. CONCLUSION: These results confirm that in a population at medium risk for colorectal cancer, the organised programme is an effective strategy for reducing its incidence. They also confirm that the achievement of European objectives remains a key issue for improving the effectiveness of organized screening. An evolution of immunological test delivery modalities could help to achieve these participation objectives.

Evidence against a role for NLRP3-driven islet inflammation in db/db mice.

OBJECTIVES: Type 2 diabetes (T2D) is associated with chronic, low grade inflammation. Activation of the NLRP3 inflammasome and secretion of its target interleukin-1ß (IL-1ß) have been implicated in pancreatic ß cell failure in T2D. Specific targeting of the NLRP3 inflammasome to prevent pancreatic ß cell death could allow for selective T2D treatment without compromising all IL-1ß-associated immune responses. We hypothesized that treating a mouse model of T2D with MCC950, a compound that specifically inhibits NLRP3, would prevent pancreatic ß cell death, thereby preventing the onset of T2D. METHODS: Diabetic db/db mice were treated with MCC950 via drinking water for 8 weeks from 6 to 14 weeks of age, a period over which they developed pancreatic ß cell failure. We assessed metabolic parameters such as body composition, glucose tolerance, or insulin secretion over the course of the intervention. RESULTS: MCC950 was a potent inhibitor of NLRP3-induced IL-1ß in vitro and was detected at high levels in the plasma of treated db/db mice. Treatment of pre-diabetic db/db mice with MCC950, however, did not prevent pancreatic dysfunction and full onset of the T2D pathology. When examining the NLRP3 pathway in the pancreas of db/db mice, we could not detect an activation of this pathway nor increased levels of its target IL-1ß. CONCLUSIONS: NLRP3 driven-pancreatic IL-1ß inflammation does not play a key role in the pathogenesis of the db/db murine model of T2D.

[Assessment of driving in patients with vertigo and dizziness]. / Fahreignungsbeurteilung bei Schwindel aus neurologischer Sicht.

The driving performance of patients with dizziness and vertigo has gained only minor attention so far. Patients with permanent vestibular loss or with episodic vestibular symptoms can experience difficulties in driving a motor vehicle. The presence of a chronic or episodic syndrome presenting with dizziness and/or vertigo does not automatically exclude the ability to drive. Assessment of driving performance should consider the degree of the deficits and compensation in chronic dysfunction and the severity and frequency of attacks, prodromes and triggers of symptoms in episodic disorders.

[Traffic medicine expert opinions in otorhinolaryngology: current aspects]. / Verkehrsmedizinische Begutachtung in der HNO-Heilkunde : Aktuelle Aspekte.

According to German law granting of driving licenses depends on the proof of an adequate driving capability. The corresponding guidelines are at present in the process of being revised. At the moment bilateral deafness and high-grade hearing loss (> or = 60% in pure tone audiometry) are not exclusion criteria for driving licenses grades A, B and C, while driving licenses grade D and licenses for public transport are generally excluded. In the forthcoming revised edition of the guidelines it has been suggested that the latter group will also not be excluded. The regulations concerning dizziness are wide-sweeping at the moment as no driving license will be granted if dizziness is present but will be more specific in the next issue. In particular a division will be made between single axle and two axle vehicles. An expert assessment about driving suitability can only be made by a certified specialist with qualifications in traffic medicine.

Saccade Velocity as a Surrogate DiseaseMarker in Spinocerebellar Ataxia Type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal-dominant disorder mani-festing with gait, limb, and speech incoordination, and with distinctive symptomssuch as early slowing of horizontal eye movements and early neuropathy.1–3 Neuro-pathological analysis has demonstrated severe olivopontocerebellar atrophy (OPCA)early in the course of disease, progressing to involve the anterior horn, substantia ni-gra, thalamus, and somatosensory pathways.4,5 Clinical onset is usually in midlife,but has been observed to range from 1 to 65 years of age, depending on the size ofthe underlying mutation, a CAG (cytosine-adenine-guanine)-trinucleotide repeat ex-pansion in exon 1 of the SCA2 gene...(AU)

Saccade velocity as a surrogate disease marker in spinocerebellar ataxia type 2.

We measured in 82 spinocerebellar ataxia type 2 (SCA2) patients and in 80 controls maximal saccade velocity (MSV) and correlated it to polyglutamine expansion size and disease duration. MSV is strongly decreased in SCA2 patients and is influenced mostly by polyglutamine size.

[Oskar Vogt (1870-1959). Hypnotist and brain researcher, husband of Cecile Vogt (1875-1962)]. / Oskar Vogt (1870-1959) Hypnotiseur und Hirnforscher, Ehemann von Cécile Vogt (1875-1962).

Oskar Vogt (1870-1955) and his wife Cecile (1875-1962) were neurologists and neuroanatomists with a strong interest in the cytoarchitectonics and myeloarchitectonics of the brain and in the functional anatomy of the basal ganglia. In the 1920s, Vogt created a multi-disciplinary brain research institute, the Kaiser-Wilhelm-Institut fur Hirnforschung in Berlin-Buch, with divisions for e.g. neuroanatomy, neurohistology, neurophysiology, neurochemistry, and genetics. Oskar Vogt's scientific activities are discussed briefly with special regard to his former co-worker Brodmann. After being dismissed from office by the Nazi government in 1937, the Vogts continued their work in a privately funded institute in Neustadt, in the Black Forest.

[Alfred Döblin (1878-1957). Notes on the cover picture]. / Alfred Döblin (1878-1957). Anmerkungen zum Titelbild.

Alfred Döblin studied medicine after completing his Abitur (A-levels). In 1905 he earned his doctorate under Alfred Hoche, director of the psychiatric clinic, by presenting a study on "Memory disorders in Korsakoff's psychosis." He subsequently worked as an assistant doctor in various psychiatric clinics until he switched to internal medicine in 1908. He opened a practice as panel doctor in 1911, which he operated until 1930. Although Döblin had already published a few stories, he first became generally known in 1929 with the appearance of his novel entitled "Berlin Alexanderplatz: the story of Franz Biberkopf." After the burning of the Reichstag in February 1933, as a Jewish socialist Döblin was forced to emigrate. He was unable to work as a physician during his exile, but remained active in his literary pursuits. Döblin died on 26 June 1957 in the state hospital in Emmendingen.

[External ophthalmoplegia caused by amitriptyline poisoning]. / Externe Ophthalmoplegie durch Amitriptylin-Intoxikation.

Drug-induced ocular motor disorders occurring during coma may be difficult to distinguish from structural cerebral lesions. We recently encountered a case of reversible amitriptyline-induced external ophthalmoplegia, which was first described by Mladinich and Carlow in 1977. We suggest that the mechanism for gaze paresis and loss of vestibulo-ocular reflex due to amitriptyline overdose involves the modulation of neurons of the pontine paramedian reticular formation, the rostral fasciculus longitudinalis medialis, and the vestibulo-ocular reflex. Clinical features that might be useful when distinguishing amitriptyline-induced ophthalmoplegia from structural brain lesions--such as basilar thrombosis--include the preservation of corneal response, purposeful withdrawal from noxious stimuli, rapid recovery within 24 hours, and the reversal of symptoms by physostigmine.

Reduced cerebrovascular CO(2) reactivity in CADASIL: A transcranial Doppler sonography study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells. To study cerebrovascular function in CADASIL, we performed measurements on cerebral hemodynamics by using transcranial Doppler sonography. METHODS: Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO(2) reactivity, and the resistance index were measured by bilateral transcranial Doppler sonography in 29 CADASIL individuals (mean age, 49.0+/-2.4 years) and an equal number of age- and sex-matched control subjects. RESULTS: Compared with control subjects, CO(2) reactivity was reduced in CADASIL (33.4+/-2.7% versus 45.3+/-3.0%; P:<0.01). This difference remained significant when only nondisabled CADASIL individuals (Rankin=0, n=21) were included in the analysis (P:<0.05). CO(2) reactivity was significantly lower in disabled than in nondisabled CADASIL individuals (24.5+/-2.7% versus 36.8+/-3.4%; P:<0.05). MCA MFV was reduced in CADASIL (45.6+/-2.2 cm/s versus 54.2+/-2.4 cm/s; P:<0.05) and correlated negatively with age both in affected individuals (r=-0.314; P:<0.05) and control subjects (r=-0.339; P:<0.05). Resistance index was not significantly altered (59.0+/-1.0% versus 57.7+/-1.2%; P:=0.42). CONCLUSIONS: In CADASIL, there is a reduction of both CO(2) reactivity and basal MCA MFV. The reduced CO(2) reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO(2) reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.

"Atraumatic" Sprotte needle reduces the incidence of post-lumbar puncture headaches.

Post-lumbar puncture headache (PLPH) is best explained by spinal fluid leakage due to delayed closure of a dural defect. In a prospective, randomized, double-blind study, taking into consideration all known methodological problems, the authors compared the incidence of PLPH using the "atraumatic" Sprotte needle vs the "traumatic" Quincke needle. Of the 230 patients included in the final analysis, 24.4% of patients in the "traumatic" group developed PLPH, whereas only 12.2% of patients in the "atraumatic" group did (p < 0.05). Therefore, use of the "atraumatic" Sprotte needle for lumbar puncture is recommended.