Mandatory infectious diseases consultation for MRSA bacteremia is associated with reduced mortality.

OBJECTIVES: Although infectious disease (ID) consultation has been associated with lower mortality in Staphylococcus aureus bloodstream infections, it is still not mandatory in many centers. This study aimed at assessing the impact of ID consultation on diagnostic and therapeutic management of methicillin-resistant S. aureus (MRSA) bacteremia. METHODS: Retrospective cohort study of all patients with MRSA bacteremia from 2001 to 2010. ID consultations were obtained on request between 2001 and 2006 and became mandatory since 2007. RESULTS: 156 episodes of MRSA bacteremia were included, mostly from central venous catheter (32%) and skin and soft tissue (19%) infections. ID consultation coverage was 58% between 2001 and 2006 and 91% between 2007 and 2010. ID consultation was associated with more echocardiography (59% vs. 26%, p < 0.01), vancomycin trough level measurements (99% vs. 77%, p < 0.01), follow-up blood cultures (71% vs. 50%, p = 0.05), deep-seated infections (43% vs. 16%, p < 0.01), more frequent infection source control (83% vs. 57%, p = 0.03), a longer duration of MRSA-active therapy (median and IQR: 17 days, 13-30, vs. 12, 3-14, p < 0.01) and a 20% reduction in 7-day, 30-day and in-hospital mortality. CONCLUSIONS: ID consultation was associated with a better management of patients with MRSA bacteremia and a reduced mortality.

Individual prediction of automobile bodily injury claims liabilities

[spa] La mayoría de siniestros con daños corporales se liquidan mediante negociación, llegando a juicio menos del 5% de los casos. Una estrategia de negociación bien definida es, por tanto, fundamental para las compañías aseguradoras. En este artículo asumimos que la compensación monetaria concedida en juicio es la máxima cuantía que debería ser ofrecida por el asegurador en el proceso de negociación. Usando una base de datos real, implementamos un modelo log-lineal para estimar la máxima oferta de negociación. Perturbaciones no-esféricas son detectadas. Correlación ocurre cuando más de una siniestro se liquida en la misma sentencia judicial. Heterocedasticidad por grupos se debe a la influencia de la valoración del forense en la indemnización final.

Trends in mortality from coronary heart and cerebrovascular disease in Switzerland, 1969-87.

Trends in age-specific and age-standardized death certification rates from all ischaemic heart disease and cerebrovascular disease in Switzerland have been analysed for the period 1969-87, i.e. since the introduction of the Eighth Revision of the International Classification of Diseases for coding causes of death. For coronary heart disease, overall age-standardized rates of males in the mid-late 1980's were similar to those in the late 1960's, although some upward trend was evident up to the mid 1970's (with a peak rate of 120.4/100,000, World standard, in 1978) followed by steady declines in more recent years (103.8/100,000 in 1987). These falls were larger in truncated (35 to 64 years) rates. For females, overall age-standardized rates were stable around a value of 40/100,000, while truncated rates tended to decrease, particularly over most recent years, with an overall decline of over 25%. Examination of age-specific trends showed that in both sexes declines at younger ages were already evident in the earlier calendar period, while above age 50 some fall became evident only in most recent years. Thus, in a formal log-linear age/period/cohort model, both a period and a cohort component emerged. In relation to cerebrovascular diseases, the overall declines were around 40% in males (from 67.4 to 41.2/100,000, World standard) and 45% for females (from 56.6 to 31.7/100,000), and were proportionally comparable across subsequent age groups above age 45. The estimates for the age/period/cohort model were thus downwards both for the period and the cohort component although, in such a situation, it is difficult to disentangle the major underlying component.(ABSTRACT TRUNCATED AT 250 WORDS)

Invasive Candida infections in the ICU

Invasive candidiasis, including candidemia and deep-seated Candida infections, is a severe opportunistic infection with an overall mortality in ICU patients comparable to that of severe sepsis/septic shock. With an incidence ranging from 5 to 10 cases per 1000 ICU admissions, invasive candidiasis represents 510% of all ICU-acquired infections. Although a high proportion of critically ill patients is colonised with Candida spp., only 540% develop an invasive infection. The occurrence of this complication is difficult to predict and an early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New non-culture based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Recent data suggest that prediction rules based on risk factors, clinical and microbiological parameters or monitoring of Candida colonisation may efficiently identify critically ill patients at high risk of invasive candidiasis who may benefit of preventive or pre-emptive antifungal therapy. In many cancer centres, exposure to azoles antifungals has been associated with an epidemiological shift from Candida albicans to non-albicans Candida species with reduced antifungal susceptibility or intrinsic resistance. This trend has not been observed in recent surveys on candidemia in non-immunocompromised ICU patients. Prophylaxis, pre-emptive or empirical antifungal treatment are possible approaches for prevention or early management of invasive candidiasis. However, the selection of high-risk patients remains critical for an efficient management aimed at reducing the number needed to treat and thus avoiding unnecessary treatments associated with the emergence of resistance, drug toxicity and costs.

The pneumonia severity index: a decade after the initial derivation and validation

The prognosis of community-acquired pneumonia ranges from rapid resolution of symptoms and full recovery of functional status to the development of severe medical complications and death. The pneumonia severity index is a rigorously studied prediction rule for prognosis that objectively stratifies patients into quintiles of risk for short-term mortality on the basis of 20 demographic and clinical variables routinely available at presentation. The pneumonia severity index was derived and validated with data on >50,000 patients with community-acquired pneumonia by use of well-accepted methodological standards and is the only pneumonia decision aid that has been empirically shown to safely increase the proportion of patients given treatment in the outpatient setting. Because of its prognostic accuracy, methodological rigor, and effectiveness and safety as a decision aid, the pneumonia severity index has become the reference standard for risk stratification of community-acquired pneumonia

Optimal growth strategies when mortality and production rates are size-dependent

Pontryagin's maximum principle from optimal control theory is used to find the optimal allocation of energy between growth and reproduction when lifespan may be finite and the trade-off between growth and reproduction is linear. Analyses of the optimal allocation problem to date have generally yielded bang-bang solutions, i.e. determinate growth: life-histories in which growth is followed by reproduction, with no intermediate phase of simultaneous reproduction and growth. Here we show that an intermediate strategy (indeterminate growth) can be selected for if the rates of production and mortality either both increase or both decrease with increasing body size, this arises as a singular solution to the problem. Our conclusion is that indeterminate growth is optimal in more cases than was previously realized. The relevance of our results to natural situations is discussed.

Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

BACKGROUND: Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. METHODS: BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.govNCT00004205. FINDINGS: 8010 patients were included in the trial, with a median follow-up of 8·1 years (range 0-12·4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8·7 years from randomisation (range 0-12·4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0·82 [95% CI 0·74-0·92], overall survival HR 0·79 [0·69-0·90], DRFI HR 0·79 [0·68-0·92], BCFI HR 0·80 [0·70-0·92]; intention-to-treat disease-free survival HR 0·86 [0·78-0·96], overall survival HR 0·87 [0·77-0·999], DRFI HR 0·86 [0·74-0·998], BCFI HR 0·86 [0·76-0·98]). At a median follow-up of 8·0 years from randomisation (range 0-11·2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE ≤1·1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78·6%, 77·8%, 77·3% for disease-free survival; 87·5%, 87·7%, 85·9% for overall survival; 89·9%, 88·7%, 88·1% for DRFI; and 86·1%, 85·3%, 84·3% for BCFI. INTERPRETATION: For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability. FUNDING: Novartis, United States National Cancer Institute, International Breast Cancer Study Group.

Prediction markets supporting technology assessment

In this thesis, we study the use of prediction markets for technology assessment. We particularly focus on their ability to assess complex issues, the design constraints required for such applications and their efficacy compared to traditional techniques. To achieve this, we followed a design science research paradigm, iteratively developing, instantiating, evaluating and refining the design of our artifacts. This allowed us to make multiple contributions, both practical and theoretical. We first showed that prediction markets are adequate for properly assessing complex issues. We also developed a typology of design factors and design propositions for using these markets in a technology assessment context. Then, we showed that they are able to solve some issues related to the R&D portfolio management process and we proposed a roadmap for their implementation. Finally, by comparing the instantiation and the results of a multi-criteria decision method and a prediction market, we showed that the latter are more efficient, while offering similar results. We also proposed a framework for comparing forecasting methods, to identify the constraints based on contingency factors. In conclusion, our research opens a new field of application of prediction markets and should help hasten their adoption by enterprises. Résumé français: Dans cette thèse, nous étudions l'utilisation de marchés de prédictions pour l'évaluation de nouvelles technologies. Nous nous intéressons plus particulièrement aux capacités des marchés de prédictions à évaluer des problématiques complexes, aux contraintes de conception pour une telle utilisation et à leur efficacité par rapport à des techniques traditionnelles. Pour ce faire, nous avons suivi une approche Design Science, développant itérativement plusieurs prototypes, les instanciant, puis les évaluant avant d'en raffiner la conception. Ceci nous a permis de faire de multiples contributions tant pratiques que théoriques. Nous avons tout d'abord montré que les marchés de prédictions étaient adaptés pour correctement apprécier des problématiques complexes. Nous avons également développé une typologie de facteurs de conception ainsi que des propositions de conception pour l'utilisation de ces marchés dans des contextes d'évaluation technologique. Ensuite, nous avons montré que ces marchés pouvaient résoudre une partie des problèmes liés à la gestion des portes-feuille de projets de recherche et développement et proposons une feuille de route pour leur mise en oeuvre. Finalement, en comparant la mise en oeuvre et les résultats d'une méthode de décision multi-critère et d'un marché de prédiction, nous avons montré que ces derniers étaient plus efficaces, tout en offrant des résultats semblables. Nous proposons également un cadre de comparaison des méthodes d'évaluation technologiques, permettant de cerner au mieux les besoins en fonction de facteurs de contingence. En conclusion, notre recherche ouvre un nouveau champ d'application des marchés de prédiction et devrait permettre d'accélérer leur adoption par les entreprises.

Polypharmacy as predictor of drug cost, length of hospital stay and mortality rate in nursing homes : a retrospective analysis of pharmacy medication records

Background and objectives: Polypharmacy (PP) is a typical con-sequence of multiple chronic conditions in elderly patients. PP is commonly defined as the use of multiple concurrent drug therapies although a standard definition is not used. The aims of this study were to assess the PP rate among nursing home (NH) residents using the data of the pharmacy medication records and to investigate the threshold level of PP as predictor of drug cost, length of hospital stay and mortality rate

Diagnosis of invasive candidiasis in the ICU.

Invasive candidiasis ranges from 5 to 10 cases per 1,000 ICU admissions and represents 5% to 10% of all ICU-acquired infections, with an overall mortality comparable to that of severe sepsis/septic shock. A large majority of them are due to Candida albicans, but the proportion of strains with decreased sensitivity or resistance to fluconazole is increasingly reported. A high proportion of ICU patients become colonized, but only 5% to 30% of them develop an invasive infection. Progressive colonization and major abdominal surgery are common risk factors, but invasive candidiasis is difficult to predict and early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New nonculture-based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Both serologic (mannan, antimannan, and betaglucan) and molecular (Candida-specific PCR in blood and serum) have been applied as serial screening procedures in high-risk patients. However, although reasonably sensitive and specific, these techniques are largely investigational and their clinical usefulness remains to be established. Identification of patients susceptible to benefit from empirical antifungal treatment remains challenging, but it is mandatory to avoid antifungal overuse in critically ill patients. Growing evidence suggests that monitoring the dynamic of Candida colonization in surgical patients and prediction rules based on combined risk factors may be used to identify ICU patients at high risk of invasive candidiasis susceptible to benefit from prophylaxis or preemptive antifungal treatment.