Reproductive inequality in humans and other mammals.

To address claims of human exceptionalism, we determine where humans fit within the greater mammalian distribution of reproductive inequality. We show that humans exhibit lower reproductive skew (i.e., inequality in the number of surviving offspring) among males and smaller sex differences in reproductive skew than most other mammals, while nevertheless falling within the mammalian range. Additionally, female reproductive skew is higher in polygynous human populations than in polygynous nonhumans mammals on average. This patterning of skew can be attributed in part to the prevalence of monogamy in humans compared to the predominance of polygyny in nonhuman mammals, to the limited degree of polygyny in the human societies that practice it, and to the importance of unequally held rival resources to women's fitness. The muted reproductive inequality observed in humans appears to be linked to several unusual characteristics of our species-including high levels of cooperation among males, high dependence on unequally held rival resources, complementarities between maternal and paternal investment, as well as social and legal institutions that enforce monogamous norms.

Innovative teaching knowledge stays with users.

Programs seeking to transform undergraduate science, technology, engineering, and mathematics courses often strive for participating faculty to share their knowledge of innovative teaching practices with other faculty in their home departments. Here, we provide interview, survey, and social network analyses revealing that faculty who use innovative teaching practices preferentially talk to each other, suggesting that greater steps are needed for information about innovative practices to reach faculty more broadly.

Antimicrobial prescribing by Belgian dentists in ambulatory care, from 2010 to 2016.

OBJECTIVES: To describe antimicrobial prescribing by Belgian dentists in ambulatory care, from 2010 until 2016. MATERIALS AND METHODS: Reimbursement data from the Belgian National Institute for Health and Disability Insurance were analysed to evaluate antimicrobial prescribing (WHO ATC-codes J01/P01AB). Utilisation was expressed in defined daily doses (DDDs), and in DDDs and packages per 1000 inhabitants per day (DID and PID, respectively). Additionally, the number of DDD and packages per prescriber was calculated. RESULTS: In 2016, the dentistry-related prescribing rate of 'Antibacterials for systemic use' (J01) and 'Antiprotozoals' (P01AB) was 1.607 and 0.014 DID, respectively. From 2010 to 2016, the DID rate of J01 increased by 6.3%, while the PID rate declined by 6.7%. Amoxicillin and amoxicillin with an enzyme inhibitor were the most often prescribed products, followed by clindamycin, clarithromycin, doxycycline, azithromycin and metronidazole. The proportion of amoxicillin relative to amoxicillin with an enzyme inhibitor was low. The narrow-spectrum antibiotic penicillin V was almost never prescribed. CONCLUSIONS: Antibiotics typically classified as broad- or extended-spectrum were prescribed most often by Belgian dentists during the period 2000-2016. Although the DID rate of all 'Antibacterials for systemic use' (J01) increased over the years, the number of prescriptions per dentist decreased since 2013. The high prescription level of amoxicillin with an enzyme inhibitor is particularly worrying. It indicates that there is a need for comprehensive clinical practice guidelines for Belgian dentists.

Augmented and doubly robust G-estimation of causal effects under a Structural nested failure time model.

Structural nested failure time models (SNFTMs) are models for the effect of a time-dependent exposure on a survival outcome. They have been introduced along with so-called G-estimation methods to provide valid adjustment for time-dependent confounding induced by time-varying variables. Adjustment for informative censoring in SNFTMs is possible via inverse probability of censoring weighting (IPCW). In the presence of considerable dropout, this can imply substantial information loss and consequently imprecise effect estimates. In this article, we aim to increase the efficiency of IPCW G-estimators under a SNFTM by deriving an augmented estimator that uses both censored and uncensored observations, and offers robustness against misspecification of the model for the censoring process, provided that a model for a specific functional of the survival time and time-dependent covariates is correctly specified. The empirical properties of the proposed estimators are studied in a simulation experiment, and the estimators are used in the analysis of surveillance data from the field of hospital epidemiology.

Validation of a Sampling Method to Collect Exposure Data for Central-Line-Associated Bloodstream Infections.

OBJECTIVE: Surveillance of central-line-associated bloodstream infections requires the labor-intensive counting of central-line days (CLDs). This workload could be reduced by sampling. Our objective was to evaluate the accuracy of various sampling strategies in the estimation of CLDs in intensive care units (ICUs) and to establish a set of rules to identify optimal sampling strategies depending on ICU characteristics. DESIGN: Analyses of existing data collected according to the European protocol for patient-based surveillance of ICU-acquired infections in Belgium between 2004 and 2012. SETTING AND PARTICIPANTS: CLD data were reported by 56 ICUs in 39 hospitals during 364 trimesters. METHODS: We compared estimated CLD data obtained from weekly and monthly sampling schemes with the observed exhaustive CLD data over the trimester by assessing the CLD percentage error (ie, observed CLDs - estimated CLDs/observed CLDs). We identified predictors of improved accuracy using linear mixed models. RESULTS: When sampling once per week or 3 times per month, 80% of ICU trimesters had a CLD percentage error within 10%. When sampling twice per week, this was >90% of ICU trimesters. Sampling on Tuesdays provided the best estimations. In the linear mixed model, the observed CLD count was the best predictor for a smaller percentage error. The following sampling strategies provided an estimate within 10% of the actual CLD for 97% of the ICU trimesters with 90% confidence: 3 times per month in an ICU with >650 CLDs per trimester or each Tuesday in an ICU with >480 CLDs per trimester. CONCLUSION: Sampling of CLDs provides an acceptable alternative to daily collection of CLD data.

Preventable proportion of severe infections acquired in intensive care units: case-mix adjusted estimations from patient-based surveillance data.

BACKGROUND: More than 10% of patients admitted to intensive care units (ICUs) experience a severe, healthcare-associated infection, such as ventilator-associated pneumonia (VAP) or bloodstream infection (BSI). What could be a public health target for prevention is hotly debated, because properly adjusting for intrinsic risk factors in the patient population is difficult. We aimed to estimate the proportion of ICU-acquired VAP and BSI cases that are amenable to prevention in routine conditions. METHODS: We analyzed routine data collected prospectively according to the European standard protocol for patient-based surveillance of healthcare-acquired infections in ICUs. We computed the number of infections to be expected if, after adjustment for case mix, the infection incidence in ICUs with higher infection rates could be reduced to that of the top-tenth-percentile-ranked ICU. Computations came from model-based simulation of individual patient profiles over time in the ICU. The preventable proportion was computed as the number of observed cases minus the number of expected cases divided by the number of observed cases. RESULTS: Data for 78,222 patients admitted for more than 2 days to 525 ICUs in 6 European countries from 2005 to 2008 were available for analysis. We calculated that 52% of VAP and 69% of BSI was preventable. CONCLUSIONS: Our pragmatic, if highly conservative, estimates quantify the potential for prevention of VAP and BSI in routine conditions, assuming that variation in infection incidence between ICUs can be eliminated with improved quality of care, apart from variation attributable to differential case mix.

Risk factors for methicillin resistant Staphylococcus aureus: a multi-laboratory study.

BACKGROUND: The present study aimed to investigate the dose response relationship between the prescriptions of antimicrobial agents and infection/colonization with methicillin resistant Staphylococcus aureus (MRSA) taking additional factors like stay in a health care facility into account. METHODS: Multi-centre retrospective study on a cohort of patients that underwent microbiological diagnostics in Belgium during 2005. The bacteriological results retrieved from 17 voluntary participating clinical laboratories were coupled with the individual antimicrobial consumption patterns (July 2004-December 2005) and other variables as provided by pooled data of health insurance funds. Multivariate analysis was used to identify risk factors for MRSA colonization/infection. RESULTS: A total of 6844 patients of which 17.5% died in the year 2005, were included in a logistic regression model. More than 97% of MRSA was associated with infection (clinical samples), and only a minority with screening/colonization (1.59%). Factors (95% CI) significantly (p≤<0.01) associated with MRSA in the final multivariate model were: admission to a long term care settings (2.79-4.46); prescription of antibiotics via a hospital pharmacy (1.30-2.01); age 55+ years (3.32-5.63); age 15-54 years (1.23-2.16); and consumption of antimicrobial agent per DDD (defined daily dose) (1.25-1.40). CONCLUSIONS: The data demonstrated a direct dose-response relationship between MRSA and consumption of antimicrobial agents at the individual patient level of 25-40% increased risk per every single day. In addition the study indicated an involvement of specific healthcare settings and age in MRSA status.

Parenteral versus oral administration of systemic antimicrobials in European nursing homes: a point-prevalence survey.

BACKGROUND: Residents in long-term care facilities are predisposed to healthcare-associated infections that are likely caused by antimicrobial-resistant micro-organisms. Long-term care facilities are increasingly able to offer parenteral antimicrobial treatment but there are few data on the use and appropriateness of such treatment in this setting. Information on the use of parenteral antimicrobials and associated factors in long-term care facilities is necessary to assess the risks and benefits of this treatment and to support the development of antimicrobial policies aimed at minimizing the emergence and spread of antimicrobial resistance. OBJECTIVE: The aim of this study was to describe the extent of parenteral and oral antimicrobial use in participating European nursing homes (NHs) and to analyse the resident characteristics and determinants associated with route of antimicrobial administration. METHODS: Data on resident characteristics and antimicrobials were collected by means of a point-prevalence survey. Logistic regression was used to analyse the data. RESULTS: Based on data from 21 European countries for 2046 antimicrobial prescriptions, an average of 9.0% (range by country: 0.0-66.7%) of treatment was administered parenterally. Multivariate analysis showed that residents receiving parenteral antimicrobials had greater morbidity, such as increased risk of having a urinary catheter (p < 0.001), a vascular catheter (p < 0.001), impaired mobility (p = 0.007) and disorientation (p = 0.005). Residents receiving parenteral antimicrobials also had been admitted more recently into the NH (p = 0.007). Empirical treatment of respiratory tract infections (RTIs) accounted for the majority of parenteral antimicrobials, while prophylaxis of urinary tract infection (UTI) was the most common indication for oral antimicrobials. Beta-lactam antibacterials (cephalosporins and aminopenicillins) were the predominant classes used. CONCLUSIONS: Our study showed that risk and care-load factors (i.e. the presence of a urinary or vascular catheter, impaired mobility, disorientation and relatively short length of stay) were associated with parenteral administration of antimicrobials in NHs. Furthermore, both the indication and the class of antimicrobial agent used were associated with administration route. For empirical treatment of RTIs, antimicrobials were most often administered parenterally.

Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study.

BACKGROUND: Patients admitted to intensive-care units are at high risk of health-care-associated infections, and many are caused by antimicrobial-resistant pathogens. We aimed to assess excess mortality and length of stay in intensive-care units from bloodstream infections and pneumonia. METHODS: We analysed data collected prospectively from intensive-care units that reported according to the European standard protocol for surveillance of health-care-associated infections. We focused on the most frequent causative microorganisms. Resistance was defined as resistance to ceftazidime (Acinetobacter baumannii or Pseudomonas aeruginosa), third-generation cephalosporins (Escherichia coli), and oxacillin (Staphylococcus aureus). We defined 20 different exposures according to infection site, microorganism, and resistance status. For every exposure, we compared outcomes between patients exposed and unexposed by use of time-dependent regression modelling. We adjusted results for patients' characteristics and time-dependency of the exposure. FINDINGS: We obtained data for 119 699 patients who were admitted for more than 2 days to 537 intensive-care units in ten countries between Jan 1, 2005, and Dec 31, 2008. Excess risk of death (hazard ratio) for pneumonia in the fully adjusted model ranged from 1·7 (95% CI 1·4-1·9) for drug-sensitive S aureus to 3·5 (2·9-4·2) for drug-resistant P aeruginosa. For bloodstream infections, the excess risk ranged from 2·1 (1·6-2·6) for drug-sensitive S aureus to 4·0 (2·7-5·8) for drug-resistant P aeruginosa. Risk of death associated with antimicrobial resistance (ie, additional risk of death to that of the infection) was 1·2 (1·1-1·4) for pneumonia and 1·2 (0·9-1·5) for bloodstream infections for a combination of all four microorganisms, and was highest for S aureus (pneumonia 1·3 [1·0-1·6], bloodstream infections 1·6 [1·1-2·3]). Antimicrobial resistance did not significantly increase length of stay; the hazard ratio for discharge, dead or alive, for sensitive microorganisms compared with resistant microorganisms (all four combined) was 1·05 (0·97-1·13) for pneumonia and 1·02 (0·98-1·17) for bloodstream infections. P aeruginosa had the highest burden of health-care-acquired infections because of its high prevalence and pathogenicity of both its drug-sensitive and drug-resistant strains. INTERPRETATION: Health-care-associated bloodstream infections and pneumonia greatly increase mortality and pneumonia increase length of stay in intensive-care units; the additional effect of the most common antimicrobial resistance patterns is comparatively low. FUNDING: European Commission (DG Sanco).

Adjusting for time-varying confounding in the subdistribution analysis of a competing risk.

Despite decades of research in the medical literature, assessment of the attributable mortality due to nosocomial infections in the intensive care unit (ICU) remains controversial, with different studies describing effect estimates ranging from being neutral to extremely risk increasing. Interpretation of study results is further hindered by inappropriate adjustment (a) for censoring of the survival time by discharge from the ICU, and (b) for time-dependent confounders on the causal path from infection to mortality. In previous work (Vansteelandt et al. Biostatistics 10:46-59), we have accommodated this through inverse probability of treatment and censoring weighting. Because censoring due to discharge from the ICU is so intimately connected with a patient's health condition, the ensuing inverse weighting analyses suffer from influential weights and rely heavily on the assumption that one has measured all common risk factors of ICU discharge and mortality. In this paper, we consider ICU discharge as a competing risk in the sense that we aim to infer the risk of 'ICU mortality' over time that would be observed if nosocomial infections could be prevented for the entire study population. For this purpose we develop marginal structural subdistribution hazard models with accompanying estimation methods. In contrast to subdistribution hazard models with time-varying covariates, the proposed approach (a) can accommodate high-dimensional confounders, (b) avoids regression adjustment for post-infection measurements and thereby so-called collider-stratification bias, and (c) results in a well-defined model for the cumulative incidence function. The methods are used to quantify the causal effect of nosocomial pneumonia on ICU mortality using data from the National Surveillance Study of Nosocomial Infections in ICU's (Belgium).

Marginal structural models for partial exposure regimes.

Intensive care unit (ICU) patients are highly susceptible to hospital-acquired infections due to their poor health and many invasive therapeutic treatments. The effect on mortality of acquiring such infections is, however, poorly understood. Our goal is to quantify this using data from the National Surveillance Study of Nosocomial Infections in ICUs (Belgium). This is challenging because of the presence of time-dependent confounders, such as mechanical ventilation, which lie on the causal path from infection to mortality. Standard statistical analyses may be severely misleading in such settings and have shown contradictory results. Inverse probability weighting for marginal structural models may instead be used but is not directly applicable because these models parameterize the effect of acquiring infection on a given day in ICU, versus "never" acquiring infection in ICU, and this is ill-defined when ICU discharge precedes that day. Additional complications arise from the informative censoring of the survival time by hospital discharge and the instability of the inverse weighting estimation procedure. We accommodate this by introducing a new class of marginal structural models for so-called partial exposure regimes. These describe the effect on the hazard of death of acquiring infection on a given day s, versus not acquiring infection "up to that day," had patients stayed in the ICU for at least s days.

Age-related variations in acylcarnitine and free carnitine concentrations measured by tandem mass spectrometry.

BACKGROUND: The acylcarnitine profiles obtained from dried blood spots on "Guthrie cards" have been widely used for the diagnosis and follow-up of children suspected of carrying an inherited error of metabolism, but little attention has been paid to potential age-related variations in the reference values. In this study, we evaluated the variations in free carnitine and acylcarnitine concentrations with age, as measured by tandem mass spectrometry. METHODS: Filter-paper blood spots were collected from 433 healthy individuals over a period of 17 months. Eight age groups were defined: cord blood, 3-6 days (control group), 15-55 days, 2-18 months, 19-59 months, 5-10 years, 11-17 years, and 18-54 years. Free carnitine and acylcarnitines were measured for each individual. Mean values were calculated for each age group and compared with those for the control group. RESULTS: Free carnitine was significantly higher in older children than in newborns (P <0.05), but the concentrations of several acylcarnitines tended to be significantly lower in cord blood and in groups of older children than in the control group. Only minor sex-related differences were observed. CONCLUSION: Although the risk of underdiagnosis of fatty acid oxidation disorders with the use of newborn values as reference can be considered as small, in some circumstances the use of age-related reference values may have a potential impact on the diagnosis and management of inherited errors of metabolism.