L'efficacité c'est bien, l'impact c'est top [Efficacy is good, impact is great].

This article summarizes the different stages of research for the development of medical interventions and their specific characteristics in terms of design, population, resources, importance of results and scientific interest. The emphasis is focused on the two final stages of development, the effectiveness and the impact. An example from our own experience is given to illustrate the reduction of the effect of an intervention against malaria in young children at different stages of the development of the intervention, and the parallel decrease of the recognition by the scientific community of the importance of these results.

Avulsion fracture of peroneus longus tendon at the first metatarsal insertion: a case report : P16

Introduction: Isolated avulsion fracture at the plantar lateral base of the first metatarsal (M1) is very rare. Case report: A 35 year old overweight woman sustained an eversion strain of her right foot. Despite pain along M1 she was able to continue walking for three days before presenting to her family doctor. Swelling on the plantar aspect of the foot was noticed, there was also pain at eversion of the foot and extension of the ankle. Plain X-ray showed no abnormalities. A MRI showed minimal bone bruise at the basis of M1 and a partial rupture of the peroneus longus tendon at its insertion. The patient was allowed to walk with partial weight bearing with a soft ankle brace. After 6 months she presented at our hospital because of persistent pain. There was still a painful insertion of the peroneus longus but active plantarflexion of M1 was possible. Plain X-rays were poorly contributive except for a discrete flattening of the longitunal arch. CT-scan showed a non displaced fracture at the M1-basis. A protocol with partial weight-bearing in a short-leg cast and partial weight-bearing orthosis each for 6 weeks was unsuccessfully attempted. Therefore, an excision of the non healed bone fragment at the basis of M1 and a first tarsometatarsal joint arthrodesis were performed. Postoperatively the patient wore a partial weight-bearing short leg cast for 6 weeks followed by a weight-bearing short leg cast for 6 weeks with favourable outcome. Discussion: Initial internal fixation has been reported to lead to good results [1, 2]. In our case the conservative treatment failed and leaded to non union. At that time we considered as too risky (overweight) to excise the fragment and reattach the peroneus longus tendon. Therefore, we excised the fragment and fused the first tarsometatarsal joint. This procedure allowed, at least partially, to compensate for the function of the peroneus longus tendon. 1 Murakami T, et al. Avulsion fracture of the peroneus longus at the first metatarsal insertion: a case report. Br J Sports Med. 2004. 2 Kwak HY, and Bae SW. Isolated avulsion fracture at the plantar lateral base of the first metatarsal: a case report. Foot Ankle Int 2000.

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH METHODS: For the most recent update, we searched the Cochrane Collaboration Tobacco Addiction Group Specialized Register in July 2012 for studies added since the last update in 2009. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. Results were expressed as a relative risk (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate, a pooled effect was estimated using a Mantel-Haenszel fixed-effect method. MAIN RESULTS: We included 15 trials using a variety of biomedical tests. Two pairs of trials had sufficiently similar recruitment, setting and interventions to calculate a pooled effect; there was no evidence that carbon monoxide (CO) measurement in primary care (RR 1.06, 95% CI 0.85 to 1.32) or spirometry in primary care (RR 1.18, 95% CI 0.77 to 1.81) increased cessation rates. We did not pool the other 11 trials due to the presence of substantial clinical heterogeneity. Of the remaining 11 trials, two trials detected statistically significant benefits: one trial in primary care detected a significant benefit of lung age feedback after spirometry (RR 2.12, 95% CI 1.24 to 3.62) and one trial that used ultrasonography of carotid and femoral arteries and photographs of plaques detected a benefit (RR 2.77, 95% CI 1.04 to 7.41) but enrolled a population of light smokers and was judged to be at unclear risk of bias in two domains. Nine further trials did not detect significant effects. One of these tested CO feedback alone and CO combined with genetic susceptibility as two different interventions; none of the three possible comparisons detected significant effects. One trial used CO measurement, one used ultrasonography of carotid arteries and two tested for genetic markers. The four remaining trials used a combination of CO and spirometry feedback in different settings. AUTHORS' CONCLUSIONS: There is little evidence about the effects of most types of biomedical tests for risk assessment on smoking cessation. Of the fifteen included studies, only two detected a significant effect of the intervention. Spirometry combined with an interpretation of the results in terms of 'lung age' had a significant effect in a single good quality trial but the evidence is not optimal. A trial of carotid plaque screening using ultrasound also detected a significant effect, but a second larger study of a similar feedback mechanism did not detect evidence of an effect. Only two pairs of studies were similar enough in terms of recruitment, setting, and intervention to allow meta-analyses; neither of these found evidence of an effect. Mixed quality evidence does not support the hypothesis that other types of biomedical risk assessment increase smoking cessation in comparison to standard treatment. There is insufficient evidence with which to evaluate the hypothesis that multiple types of assessment are more effective than single forms of assessment.

The co-evolution of social institutions, demography, and large-scale human cooperation.

Human cooperation is typically coordinated by institutions, which determine the outcome structure of the social interactions individuals engage in. Explaining the Neolithic transition from small- to large-scale societies involves understanding how these institutions co-evolve with demography. We study this using a demographically explicit model of institution formation in a patch-structured population. Each patch supports both social and asocial niches. Social individuals create an institution, at a cost to themselves, by negotiating how much of the costly public good provided by cooperators is invested into sanctioning defectors. The remainder of their public good is invested in technology that increases carrying capacity, such as irrigation systems. We show that social individuals can invade a population of asocials, and form institutions that support high levels of cooperation. We then demonstrate conditions where the co-evolution of cooperation, institutions, and demographic carrying capacity creates a transition from small- to large-scale social groups.

Characteristics and early and long-term outcome in patients with acute ischemic stroke and low ejection fraction.

OBJECTIVES: We assessed the clinical characteristics of patients with acute ischemic stroke (AIS) with left ventricular ejection fraction (EF) ≤ 35% and investigated the association of low EF with early and long-term outcome. METHODS: A total of 2439 patients of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) were selected. Demographics, risk factors, pre-stroke treatment, and clinical, radiological and metabolic variables in patients with and without low EF were compared. Functional independence (modified Rankin Score ≤ 2) and mortality were recorded 1 week up to 12 months from admission. RESULTS: Low EF patients (n=119) were more commonly men, older, had higher rates of coronary artery disease and atrial fibrillation (AF), and more frequent pretreatment with anticoagulants, antiplatelets and antihypertensive agents. On admission, they presented with higher stroke severity and had lower values of systolic blood pressure, higher heart rate, and worse estimated glomerular filtration rate. Stroke-related disability and death rates were higher in low EF patients during follow-up (19.5% vs. 7.8% at 1 week, and 36.1% vs. 16.5% at 12 months). Increasing age, stroke severity, and AF were independent predictors of one-year mortality in these patients while prior use of statins had a favorable effect on early mortality. CONCLUSIONS: AIS in patients with low EF is associated with older age, cardiac comorbidities, and more severe clinical presentation. Low EF can identify a subset of AIS patients at high risk of early and long-term functional disability and mortality.

Nonunion after fracture of the anterior tibial spine: case report and review of the literature.

Nonunion of anterior tibial spine of tibia in children is quite rare, but it could be associated with significant instability of the knee as it involves the fixation of anterior cruciate ligament. We report one case in which open reduction and internal fixation was carried out with good functional results. A literature review was performed to identify the cases reported of tibial eminence nonunion in children.

Hormonothérapie dans le cancer du sein: efficacité et effets adverses [Endocrine therapy in breast cancer: efficacy and adverse events].

Endocrine therapy remains a mainstay in the treatment of endocrine-sensitive breast cancer. In the adjuvant setting, 5 years of endocrine therapy significantly reduces recurrence rate and mortality. Tamoxifen is the molecule of choice for premenopausal women, whereas for postmenopausal women aromatase inhibitors are currently part of the standard treatment. Endocrine therapy can induce side effects, which can affect patient's quality of life and lead to premature treatment interruption. Identification and adequately addressing these side effects is fundamental to maintain good treatment compliance and therefore improve breast cancer specific outcome.

Subclinical hypothyroidism and functional mobility in older adults.

BACKGROUND: Health risks associated with subclinical hypothyroidism in older adults are unclear. Our objective was to compare the functional mobility of people aged 70 to 79 years by thyroid function categorized by thyrotropin (TSH) level as euthyroid (>or=0.4 to <4.5 mIU/L), mild subclinical hypothyroid (>or=4.5 to <7.0 mIU/L), or moderate subclinical hypothyroid (>or=7.0 to <or=20.0 mIU/L with a normal free thyroxine level) cross-sectionally and over 2 years. METHODS: A total of 2290 community-dwelling residents participating in the year 2 clinic visit (July 1998-June 1999) of the Health, Aging, and Body Composition (Health ABC) Study, who had measured TSH level, had the capacity to walk 20 m unaided, and were not taking thyroid medication or had TSH levels consistent with hyperthyroidism or hypothyroidism. Main outcome measures included self-reported and performance-based measures of mobility (usual and rapid gait speed and endurance walking ability) assessed at study baseline (year 2) and 2 years later. RESULTS: In age- and sex-adjusted analyses, the mild subclinical hypothyroid group (vs the euthyroid group) demonstrated better mobility (faster mean usual and rapid gait speed [1.20 vs 1.15 m/s and 1.65 vs 1.56 m/s, respectively; P < .001] and had a higher percentage of those with good cardiorespiratory fitness and reported walking ease [39.2% vs 28.0% and 44.7% vs 36.5%, respectively; P < .001]). After 2 years, persons with mild subclinical hypothyroidism experienced a similar decline as the euthyroid group but maintained their mobility advantage. Persons with moderate subclinical hypothyroidism had similar mobility and mobility decline as the euthyroid group. CONCLUSION: Generally, well-functioning 70- to 79-year-old individuals with subclinical hypothyroidism do not demonstrate increased risk of mobility problems, and those with mild elevations in TSH level show a slight functional advantage.

Abdominal infections in the intensive care unit: characteristics, treatment and determinants of outcome.

BACKGROUND: Abdominal infections are frequent causes of sepsis and septic shock in the intensive care unit (ICU) and are associated with adverse outcomes. We analyzed the characteristics, treatments and outcome of ICU patients with abdominal infections using data extracted from a one-day point prevalence study, the Extended Prevalence of Infection in the ICU (EPIC) II. METHODS: EPIC II included 13,796 adult patients from 1,265 ICUs in 75 countries. Infection was defined using the International Sepsis Forum criteria. Microbiological analyses were performed locally. Participating ICUs provided patient follow-up until hospital discharge or for 60 days. RESULTS: Of the 7,087 infected patients, 1,392 (19.6%) had an abdominal infection on the study day (60% male, mean age 62 ± 16 years, SAPS II score 39 ± 16, SOFA score 7.6 ± 4.6). Microbiological cultures were positive in 931 (67%) patients, most commonly Gram-negative bacteria (48.0%). Antibiotics were administered to 1366 (98.1%) patients. Patients who had been in the ICU for ≤ 2 days prior to the study day had more Escherichia coli, methicillin-sensitive Staphylococcus aureus and anaerobic isolates, and fewer enterococci than patients who had been in the ICU longer. ICU and hospital mortality rates were 29.4% and 36.3%, respectively. ICU mortality was higher in patients with abdominal infections than in those with other infections (29.4% vs. 24.4%, p < 0.001). In multivariable analysis, hematological malignancy, mechanical ventilation, cirrhosis, need for renal replacement therapy and SAPS II score were independently associated with increased mortality. CONCLUSIONS: The characteristics, microbiology and antibiotic treatment of abdominal infections in critically ill patients are diverse. Mortality in patients with isolated abdominal infections was higher than in those who had other infections.

Traitements de fer: preuves de t'efficacité et bonne pratique clinique [Iron therapy: proof of efficacy and good clinical practice].

Efficacy of iron therapy, whether oral or intravenous, on biological markers of body iron stores is well recognized in medical literature, but current studies are heterogeneous, of sometimes dubious quality, and rarely address clinical outcomes. Precise practical guidelines appear available only for indications related to kidney disease. First-line intravenous use is reserved for situations comprising chronic renal failure, or patients presenting with malabsorption syndromes such as in inflammatory bowel disease. In all other situations, because of the non-negligible risk of hypersensitivity reactions, intravenous iron use is considered justified only in clinically sustained indications, for patients in whom oral administration of iron is unsatisfactory or impossible.

Neurodevelopment outcome of newborns with cerebral subependymal pseudocysts at 18 and 46 months: a prospective study.

OBJECTIVES: Subependymal pseudocysts (SEPC) are cerebral periventricular cysts located on the floor of the lateral ventricle and result from regression of the germinal matrix. They are increasingly diagnosed on neonatal cranial ultrasound. While associated pathologies are reported, information about long-term prognosis is missing, and we aimed to investigate long-term follow-up of these patients. STUDY DESIGN: Newborns diagnosed with SEPC were enrolled for follow-up. Neurodevelopment outcome was assessed at 6, 18 and 46 months of age. RESULTS: 74 newborns were recruited: we found a high rate of antenatal events (63%), premature infants (66% <37 weeks, 31% <32 weeks) and twins (30%). MRI was performed in 31 patients, and cystic periventricular leukomalacia (c-PVL) was primarily falsely diagnosed in 9 of them. Underlying disease was diagnosed in 17 patients, 8 with congenital cytomegalovirus (CMV) infection, 5 with genetic and 4 with metabolic disease. Neurological examination (NE) at birth was normal for patients with SEPCs and no underlying disease, except one. Mean Developmental Quotient and IQ of these patients was 98.2 (±9.6SD; range 77-121), 94.6 (±14.2SD; 71-120) and 99.6 (±12.3SD; 76-120) at 6, 18 and 46 months of age, respectively, with no differences between the subtypes of SEPC. A subset analysis showed no outcome differences between preterm infants with or without SEPC, or between preterm of <32 GA and ≥32 GA. CONCLUSIONS: Neurodevelopment of newborns with SEPC was normal when no underlying disease was present. This study suggests that if NE is normal at birth and congenital CMV infection can be excluded, then no further investigations are needed. Moreover, it is crucial to differentiate SEPC from c-PVL which carries a poor prognosis.

An integer-based score to predict functional outcome in acute ischemic stroke: The ASTRAL score.

OBJECTIVE: To develop and validate a simple, integer-based score to predict functional outcome in acute ischemic stroke (AIS) using variables readily available after emergency room admission. METHODS: Logistic regression was performed in the derivation cohort of previously independent patients with AIS (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) to identify predictors of unfavorable outcome (3-month modified Rankin Scale score >2). An integer-based point-scoring system for each covariate of the fitted multivariate model was generated by their β-coefficients; the overall score was calculated as the sum of the weighted scores. The model was validated internally using a 2-fold cross-validation technique and externally in 2 independent cohorts (Athens and Vienna Stroke Registries). RESULTS: Age (A), severity of stroke (S) measured by admission NIH Stroke Scale score, stroke onset to admission time (T), range of visual fields (R), acute glucose (A), and level of consciousness (L) were identified as independent predictors of unfavorable outcome in 1,645 patients in ASTRAL. Their β-coefficients were multiplied by 4 and rounded to the closest integer to generate the score. The area under the receiver operating characteristic curve (AUC) of the score in the ASTRAL cohort was 0.850. The score was well calibrated in the derivation (p = 0.43) and validation cohorts (0.22 [Athens, n = 1,659] and 0.49 [Vienna, n = 653]). AUCs were 0.937 (Athens), 0.771 (Vienna), and 0.902 (when pooled). An ASTRAL score of 31 indicates a 50% likelihood of unfavorable outcome. CONCLUSIONS: The ASTRAL score is a simple integer-based score to predict functional outcome using 6 readily available items at hospital admission. It performed well in double external validation and may be a useful tool for clinical practice and stroke research.

Good genes and good luck: Ammonoid diversity and the end-Permian mass extinction

The end-Permian mass extinction removed more than 80% of marine genera. Ammonoid cephalopods were among the organisms most affected by this crisis. The analysis of a global diversity data set of ammonoid genera covering about 106 million years centered on the Permian-Triassic boundary (PTB) shows that Triassic ammonoids actually reached levels of diversity higher than in the Permian less than 2 million years after the PTB. The data favor a hierarchical rather than logistic model of diversification coupled with a niche incumbency hypothesis. This explosive and nondelayed diversification contrasts with the slow and delayed character of the Triassic biotic recovery as currently illustrated for other, mainly benthic groups such as bivalves and gastropods.

Subretinal neovascular membranes complicating uveitis : frequency, treatments and visual outcome

RESUME Les membranes néovasculaires (MNV) compliquent diverses pathologies ophtalmiques. Elles sont à l'origine d'une importante baisse de l'acuité visuelle lorsque elles se situent à proximité de la fovéa. A l'heure actuelle, peu de données relatives à leur association aux pathologies inflammatoires de l'oeil (uvéites) existent. Dans ce travail, la fréquence de MNV a été évaluée parmi 643 patients avec uvéite. Leur impact sur l'acuité visuelle ainsi que le pronostic en fonction des différents traitements effectués ont été étudiés. Les dossiers des 643 patients souffrant d'uvéite ont été étudiés. Les patients présentant une MNV ont été classés en trois groupes en fonction de l'importance de l'inflammation intraoculaire: élevée (2+ cellules dans le vitré), moyenne (1/2+ à 1+ cellules dans le vitré) ou absente (0 cellules dans le vitré). L'évolution de l'acuité visuelle fut considérée comme favorable (+VA: maintient de l'acuité visuelle ou gain d'une ou plusieurs lignes de Snellen) ou défavorable (-VA: perte d'une ou plusieurs lignes Snellen). Chez 9 patients, le traitement instauré a consisté, initialement, en l'administration orale de corticostéroïdes (CST) à haute dose qui, dans le cas d'évolution favorable (-FVA ou régression angiographique de la MNV), était arrêtée en doses dégressives. Dans les évolutions défavorables (-VA ou progression angiographique de la MNV), les CST étaient maintenus à dose moyenne en complémentation d'un traitement par thérapie laser (photothérapie dynamique (PDT), thermothérapie transpupillaire (TTT) ou laser Argon). Ce protocole thérapeutique ne fut appliqué chez trois patients en raison de la non disponibilité de PDT ou d'un diagnostic manqué d'uvéite. Douze patients sur 643 avec uvéite ont présenté une MNV. L'impact visuel moyen était de 4.5 lignes de Snellen et le temps moyen de suivi était de 19.5 mois. Deux patients avec inflammation intraoculaire élevée ont évolué favorablement sous CST seuls. Huit patients avec inflammation intraoculaire moyenne ont évolué favorablement sous CST seuls chez trois patients, alors que quatre patients ont nécessité une thérapie laser additionnelle. Le dernier patient ne fut traité que par thérapie laser sans CST (diagnostic manqué d'uvéite). Deux patients sans inflammation intraoculaire ont eu un pronostic défavorable sous CST seuls (pas d'autre alternative thérapeutique). Notre étude a démontré que les MNV sont une complication rare de l'uvéite qui, après traitement adéquat, ont un pronostic visuel relativement favorable. Bien que les CST semblent être la première modalité thérapeutique, les traitements laser devraient être adoptés tôt dans les situations d'inflammation intraoculaire moyenne ou absente.