Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe

Objectives

The aim of the study was to evaluate the long‐term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)‐, darunavir/ritonavir (DRV/r)‐, and lopinavir/ritonavir (LPV/r)‐containing regimens.

Methods

Data were analysed for 5678 EuroSIDA‐enrolled patients starting a DRV/r‐, ATZ/r‐ or LPV/r‐containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART‐naïve subjects (8%) at ritonavir‐boosted protease inhibitor (PI/r) initiation; (2) ART‐experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV‐1 RNA copies/mL; and (3) ART‐experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan–Meier and multivariable Cox models were used to compare risks of failure by PI/r‐based regimen. The main analysis was performed with intention‐to‐treat (ITT) ignoring treatment switches.

Results

The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log‐rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART‐naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment‐experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r‐based ART.

Conclusions

Although confounding by indication and calendar year cannot be completely ruled out, in ART‐experienced subjects the long‐term effectiveness of DRV/r‐containing regimens appears to be greater than that of ATZ/r and LPV/r.

     

Geriatric Care Boot Camp: An Interprofessional Education Program for Healthcare Professionals

In response to the need for interprofessional geriatrics education, a half‐day geriatric care boot camp for healthcare professionals was held that covered core concepts in geriatric medicine: delirium and dementia, medication management, palliative care, ethics, and a general overview of older adults. Aspects of the curriculum focused on interprofessional education, and the attendees and presenters were healthcare professionals from a wide variety of fields. Primary objectives were to determine changes in knowledge of core concepts in geriatrics and level of comfort in caring for older adults. Secondary objectives assessed whether participants found the interprofessional approach beneficial and whether they used or shared this information with others in their professional activities. Participants completed pre‐ and postassessment surveys. Changes in participant understanding of each core concept were statistically significant, as was the change in comfort level of participants in caring for older adults. Furthermore, attendees found the multidisciplinary perspective of the boot camp beneficial. A 3‐month follow‐up survey assessed whether attendees applied and shared information learned in their own professional activities. Half of the respondents who reported sharing universally shared core concepts. Delirium and dementia information was most frequently shared. Information was most frequently shared with students, nurses, and patients’ families. Attendees less frequently shared, or did not share, with physicians, physician assistants, social workers, physical and occupational therapists, nutritionists, and dentists. The healthcare professionals who may benefit greatly from future education programs are those with whom the boot camp information was least frequently shared; thus, they are appropriate targets for advertisements for future programs.     

Obesity and cardiometabolic disease risk factors among US adolescents with disabilities

AIM: To generate prevalence estimates of weight status and cardiometabolic disease risk factors among adolescents with and without disabilities.METHODS: Analysis of the 1999-2010 National Health and Nutrition Examination Survey data was conducted among 12-18 years old with(n = 256) and without disabilities(n = 5020). Mean values of waist circumference, fasting glucose, high-density-lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure and metabolic syndrome(Met S, ≥ 3 risk factors present) were examined by the following standardized body mass index(BMI) categories for those with and without disabilities; overweight(BMI ≥ 85th- 95 th percentile for age and sex), obesity(BMI ≥ 95 th percentile) and severe obesity(BMI ≥35 kg/m2). Linear regression models were fit with each cardiometabolic disease risk factor independently as continuous outcomes to show relationships with disability status. RESULTS: Adolescents with disabilities were significantlymore likely to be overweight(49.3%), obese(27.6%) and severely obese(12%) vs their peers without disabilities(33.1%, 17.5% and 3.6%, respectively, P ≤ 0.01 for all). A higher proportion of overweight, obese and severely obese children with disabilities had abnormal SBP, fasting lipids and glucose as well as Met S(18.9% of overweight, 32.3% of obese, 55% of severely obese) vs their peers without disabilities(9.7%, 16.8%, 36.3%, respectively). US adolescents with disabilities are over three times as likely to have Met S(OR = 3.45, 95%CI: 1.08-10.99, P = 0.03) vs their peers with no disabilities.CONCLUSION: Results show that adolescents with disabilities are disproportionately affected by obesity and poor cardiometabolic health vs their peers with no disabilities. Health care professionals should monitor the cardiometabolic health of adolescents with disabilities.     

Glycated hemoglobin A: A predictor of outcome in trauma admissions to intensive care unit

Background and Aim:

Although large studies have demonstrated the association between hyperglycemia and adverse intensive care unit (ICU) outcomes, it is yet unclear which subset of patients benefit from tight sugar control in ICU. Recent evidence suggests that stress induced hyperglycemia (SIH) and co-incidentally detected diabetes mellitus are different phenomena with different prognoses. Differentiating SIH from diabetic hyperglycemia is challenging in ICU settings. We followed a cohort of trauma patients admitted to a surgical intensive care unit (SICU) to evaluate if initial glycated hemoglobin A (HbA₁c) level predicts the outcome of admission.

Materials and Methods:

A cohort of 120 consecutive admissions to SICU following trauma were recruited and admission blood sugar and HbA₁c were measured. Outcomes were prospectively measured by blinded ICU doctors. A logistic regression model was developed to assess if HbA₁c predicts poor outcomes in these settings.

Results:

Nearly 24% of the participants had HbA₁c ≥ 6. Those with HbA₁c ≥ 6 had 3.14 times greater risk of poor outcome at the end of hospital stay when compared to those with HbA₁c < 6 and this risk increased to an odds ratio of 4.57 on adjusting for other significant predictors: Acute Physiology and Chronic Health Evaluation II, injury severity score, admission blood sugar and age at admission.

Conclusions:

Substantial proportion of trauma admissions has underlying diabetes. HbA₁c, a measure of pre admission glycaemic status is an important predictor of ICU outcome in trauma patients.     

Human preferences for sexually dimorphic faces may be evolutionarily novel

A large literature proposes that preferences for exaggerated sex typicality in human faces (masculinity/femininity) reflect a long evolutionary history of sexual and social selection. This proposal implies that dimorphism was important to judgments of attractiveness and personality in ancestral environments. It is difficult to evaluate, however, because most available data come from large-scale, industrialized, urban populations. Here, we report the results for 12 populations with very diverse levels of economic development. Surprisingly, preferences for exaggerated sex-specific traits are only found in the novel, highly developed environments. Similarly, perceptions that masculine males look aggressive increase strongly with development and, specifically, urbanization. These data challenge the hypothesis that facial dimorphism was an important ancestral signal of heritable mate value. One possibility is that highly developed environments provide novel opportunities to discern relationships between facial traits and behavior by exposing individuals to large numbers of unfamiliar faces, revealing patterns too subtle to detect with smaller samples.Inspired by evidence from nonhuman species indicating that exaggerated sex-typical traits (e.g., large antlers, peacock tails) are often attractive to mates or intimidating to rivals (1, 2), morphological sex typicality in humans (masculinity in men and femininity in women) has been the focus of considerable research into attractiveness judgments (3, 4). Facial attractiveness research has been revolutionized by this explanatory framework from the biological sciences, which proposes that attractive human faces honestly signaled mate value within ancestral environments.An influential proposal is that facial femininity is a signal of fertility in human female faces (4–9) because, within same-age women, it is associated with estrogens (10), which, in turn, are related to measures of reproductive health (11). Like ovarian function, facial femininity declines with age in adulthood (12, 13). The proposal that fertile women should be attractive to men is seemingly uncontroversial because males who discriminatively mate with fertile females should achieve a straightforward reproductive advantage over those males who do not, with all other factors being equal (6). Although direct associations between facial femininity and fertility have not been demonstrated, the consensus from Western preferences, and from the limited cross-cultural data available, is that femininity is attractive, as predicted by the fertility hypothesis (14–17). In environments where fertility is high and variable, this relationship should be even more apparent.In male faces, masculinity has been variously proposed to signal heritable disease resistance (“good genes” or “immunocompetence”) (4, 15, 18–22) and/or perceived as a cue of aggressiveness and, consequently, intrasexual competitiveness (22, 23). The “honesty” of face shape as an indicator of immunocompetence is proposed to be the result of an immunosuppressive effect of testosterone. Because testosterone influences the growth of sex-typical traits in many species (24, 25), masculine facial shape is proposed to be a costly, and thus honest, signal of male quality (22). The hypothesis that cues of heritable health should be attractive to females is widely accepted (26), although the evidence for a link between heritable health and masculinity in humans is tentative at best (22).Support for a link between masculinity and aggression is largely indirect, and it consists of an association between testosterone and both aggressive behavior (27, 28) and face shape (25), in addition to the fact that honest signaling of dominance is commonly observed in nonhuman species (3). Masculine faces are perceived as aggressive in those groups (i.e., urban, Western) where the relationship has been tested (29). Because masculinity may signal both (desirable) immunity and (potentially costly) aggression in humans, some authors have proposed that preferences for masculinity reflect women trading-off benefits of traits putatively associated with health against those traits associated with prosocial behaviors, such as parental investment (23, 30, 31).Consistent with both of these proposals, data indicate that preferences for masculinity are stronger in circumstances where indirect benefits (heritable quality) can be realized without accompanying direct costs (aggression and low paternal investment). Such circumstances include judging attractiveness in the context of a short-term (vs. a long-term) relationship (32) and in the follicular phase of the menstrual cycle when conception following intercourse is most likely (33). Masculinity is also reported to be more strongly preferred in environments with relatively high pathogen burdens (19, 30) and in environments with higher local homicide rates (23), which has been interpreted as a response to variation in the benefits of heritable disease resistance (19) and in the net benefits conferred by aggressive males under varying levels of male–male competition (23).All of this supporting evidence comes with a very important caveat; although there has been some cross-cultural work in this area (34), the majority of studies have been conducted in Western, often student, populations characterized by high levels of development and urbanization [Western, educated, industrialized, rich, and democratic; so-called WEIRD participants (35)]. Research on preferences in other groups is scant and methodologically inconsistent, using Internet-based designs or a limited cross-cultural component (7, 15–18). Because there are differences between Western/non-Western and industrial/small-scale societies in many behaviors, including aspects of visual perception and mate choice (35), this over-representation greatly limits generalizability. Perhaps most importantly, large-scale (post)industrial societies present inhabitants with large numbers of unfamiliar faces and provide venues for the efficient exchange of (visual) social information (e.g., posters, television, Internet); these factors may be instrumental in the acquisition and reinforcement of preferences (36–39). It is possible therefore that rather than being a legacy of ancestral selection pressures, preferences for dimorphism emerge in large urban groups as a byproduct of the information-processing strategies used to process large amounts of social information or in response to arbitrary cultural norms.Development also introduces an increased presence of highly differentiated social roles that arise from a greater division of labor, along with opportunities to acquire prestige without strength or aggression. Because partner preferences have been proposed to develop in response to sex-typical social roles (40, 41), it is possible that increasingly differentiated roles could influence masculinity preferences if desirable social roles not present in less developed groups are associated with facial appearance.We assessed preferences for, and trait attributions made to, faces varying in dimorphism in a cross-cultural sample of 12 groups, including non-Western, nonstudent, and small-scale societies (n = 962; Tables S1 and S2). We tested the predictions, derived from the immunocompetence handicapping hypothesis, that (i) preferences for dimorphism will be stronger in less developed groups and (ii) masculine faces would be perceived as aggressive in all populations, with perceptions in low-development groups at least as strong as in groups with high development. We estimated social development with the Human Development Index (HDI), which is a composite indicator compiled by the United Nations Development Program. To investigate which aspects of development were associated with variation in perception of our facial stimuli, we took the World Health Organization measures of years lost to disease and United Nations (UN) measures of homicide rates as proxy measures of disease burden and male intrasexual competition, respectively (both log-transformed), and UN measures of levels of urbanization. Using these national statistics almost certainly underestimates disease burden in the small-scale societies in our sample, which is a conservative estimate with regard to our hypotheses.

Table 1.

Summary information for the groups tested

Enhanced Ca2+-sensing receptor function in idiopathic pulmonary arterial hypertension

Rationale: A rise in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary arterial smooth muscle cells (PASMC) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. Increased resting [Ca(2+)](cyt) and enhanced Ca(2+) influx have been implicated in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH). Objective: We examined whether the extracellular Ca(2+)-sensing receptor (CaSR) is involved in the enhanced Ca(2+) influx and proliferation in IPAH-PASMC and whether blockade of CaSR inhibits experimental pulmonary hypertension. Methods and Results: In normal PASMC superfused with Ca(2+)-free solution, addition of 2.2 mmol/L Ca(2+) to the perfusate had little effect on [Ca(2+)](cyt). In IPAH-PASMC, however, restoration of extracellular Ca(2+) induced a significant increase in [Ca(2+)](cyt). Extracellular application of spermine also markedly raised [Ca(2+)](cyt) in IPAH-PASMC but not in normal PASMC. The calcimimetic R568 enhanced, whereas the calcilytic NPS 2143 attenuated, the extracellular Ca(2+)-induced [Ca(2+)](cyt) rise in IPAH-PASMC. Furthermore, the protein expression level of CaSR in IPAH-PASMC was greater than in normal PASMC; knockdown of CaSR in IPAH-PASMC with siRNA attenuated the extracellular Ca(2+)-mediated [Ca(2+)](cyt) increase and inhibited IPAH-PASMC proliferation. Using animal models of pulmonary hypertension, our data showed that CaSR expression and function were both enhanced in PASMC, whereas intraperitoneal injection of the calcilytic NPS 2143 prevented the development of pulmonary hypertension and right ventricular hypertrophy in rats injected with monocrotaline and mice exposed to hypoxia. Conclusions: The extracellular Ca(2+)-induced increase in [Ca(2+)](cyt) due to upregulated CaSR is a novel pathogenic mechanism contributing to the augmented Ca(2+) influx and excessive PASMC proliferation in patients and animals with pulmonary arterial hypertension.