Bias reduction in repeated-measures observational studies by the use of propensity score: The case of enteral sedation for critically ill patients

Purpose

Within the evidence-based medicine paradigm, randomized controlled trials represent the “gold standard” to produce reliable evidence. Indeed, planning and implementing randomized controlled trials in critical care medicine presents limitations because of intrinsic and structural problems. As a consequence, observational studies still occur frequently. In these cases, propensity score (PS) (probability of receiving a treatment conditional on observed covariates) is an increasingly used technique to adjust the results. Few studies addressed the specific issue of a PS correction of repeated-measures designs.

Materials and Methods

Three techniques for correcting the analysis of nonrandomized designs (matching, stratification, regression adjustment) are presented in a tutorial form and applied to a real case study: the comparison between intravenous and enteral sedative therapy in the intensive care unit setting.

Results

After showing the results before and after the use of PS, we suggest that such a tool allows to partially overcoming the bias associated with the observational nature of the study. It permits to correct the estimates for any observed covariate, while unobserved confounders cannot be controlled for.

Conclusions

Propensity score represents a useful additional tool to estimate the effects of treatments in nonrandomized studies. In the case study, an enteral sedation approach was equally effective to an intravenous regime, allowing for a lower level of sedation and spare of resources.     

Hormonal and psycho-relational aspects of sexual function during menopausal transition and at early menopause

Objective

The aim of the present observational, cross-sectional study was to examine the effects of hormonal and psycho-relational variables on sexual function during menopausal transition and at early postmenopause in women with hot flushes.

Study design

The sample comprised 138 women referred to a clinic for the treatment of hot flushes. They were categorised according to their stage of menopausal transition using the STRAW criteria: early menopausal transition (EMT) if their menstrual cycle was 7 or more days different from normal; late perimenopause (LMT) if they had experienced 60 days or more of amenorrhoea; and early postmenopause (EPM) if their amenorrhoea had lasted for at least 12 months but less than 4 years.

Main outcome measures

Sexual function was measured by using the Female Sexual Function Index (FSFI), while anxiety (state and trait), depression, eating disorder and marital adjustment were evaluated by validated self-report questionnaires. Levels of free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and estradiol (E2) were also measured.

Results

Overall sexual function varied significantly with stage of menopause, with total FSFI score less in EPM than in EMT (p = .009). A similar pattern was evident on FSFI sub-scales for sexual desire (p = .02), arousal (p = .01) orgasm (p = .01) and also pain (p = .02), but not for lubrication and satisfaction. Ratings for anxiety, depression and eating disorder did not differ across the menopausal sub-groups, and neither did ratings of marital adjustment. Both FT (p = .01) and DHEAS (p = .03) levels were slightly reduced at EPM in comparison with EMT, as were E2 levels (p = .001 EMT versus LMT; p = .0001 LMT versus EPM). In multiple regression analyses, plasma FT level was the only factor to predict FSFI full score (β = .48; p = 0.004) in women at EMT, while in women at LMT the depression score was the only factor to do so (β = −.62; p = 0.0001). The best model predicting FSFI full score at EPM included levels of DHEAS and E2 levels and state anxiety score.

Conclusions

Hormonal and some psychological variables are relevant to sexual function in symptomatic women during menopausal transition and at early menopause but their role differs with the specific stage of reproductive ageing.     

Different implication of NEDD9 genetic variant in early and late-onset Alzheimer's disease

Alzheimer's disease (AD) is a complex and multifactorial progressive neurodegenerative disease. Recently, two studies reported inconsistent results on a possible involvement of the NEDD9 (neural precursor cell expressed, developmentally down-regulated 9, 6p25-p24) as a candidate gene for the risk of developing AD and/or Parkinson's disease (PD). We analyzed the distribution of the rs760678 SNP polymorphism in 735 Italian subjects: 214 unrelated sporadic late-onset AD patients (LOAD, 64.5% females, mean age-at-onset 71.8 ± 5.2 years), 135 early-onset AD patients (EOAD, 57.3% females, mean age-at-onset 57.5 ± 5.5 years) and 386 healthy controls (68.9% females, mean age 83.4 ± 17.9 years; SD). We observed a statistically significant difference between LOAD patients and controls according to genotypes (P = 0.016) and allele frequency (P = 0.007); CC genotype was more frequent in LOAD cases (44.4%) than controls (36.0%). No difference after stratification of the data in terms of gender and status of the APOE ?4 allele was observed. In conclusion, our data do support an implication of the NEDD9 allelic variant in late-onset AD, with an independent effect of the apolipoprotein E (APOE) ?4 allele in the risk of developing AD.     

NGF protects Dorsal Root Ganglion neurons from oxaliplatin by modulating JNK/Sapk and ERK1/2

The involvement of the Mitogen-Activated Protein Kinases (MAPKs) family in platinum derivative-induced peripheral neuropathy has already been demonstrated. In particular, it has been evidenced that in Dorsal Root Ganglion (DRG) neurons prolonged exposure to oxaliplatin (OHP) induces early activation of p38 and ERK1/2, which mediate neuronal apoptosis, while the neuroprotective action of JNK/Sapk is downregulated by the drug treatment. In this study, the exposure of OHP-treated neurons to a neuroprotective stimulus, represented by a high dose of NGF, counteracts OHP-induced neuronal mortality. This effect was achieved by restoring the MAPK activation existing in untreated control cells. Increased viability occurred also after the administration of retinoic acid (RA), a pro-differentiative agent able to activate both JNK/Sapk and ERK1/2. The use of specific chemical inhibitors of MAPKs confirms the importance of this class of proteins for the neuroprotective pathway, since they reverse the protective effect. In summary, our findings assess the validity of MAPKs as the target of neuroprotective therapies during chemotherapeutic treatment. Moreover they also describe a double role for ERK1/2, depending on cellular stimulation, since it mediates neuronal apoptosis after OHP exposure. However, it is also important, as is JNK/Sapk, in preserving the correct cellular differentiation that is pivotal for neuronal survival.     

Pathogenesis of acute stroke and the role of inflammasomes

Inflammation is an innate immune response to infection or tissue damage that is designed to limit harm to the host, but contributes significantly to ischemic brain injury following stroke. The inflammatory response is initiated by the detection of acute damage via extracellular and intracellular pattern recognition receptors, which respond to conserved microbial structures, termed pathogen-associated molecular patterns or host-derived danger signals termed damage-associated molecular patterns. Multi-protein complexes known as inflammasomes (e.g. containing NLRP1, NLRP2, NLRP3, NLRP6, NLRP7, NLRP12, NLRC4, AIM2 and/or Pyrin), then process these signals to trigger an effector response. Briefly, signaling through NLRP1 and NLRP3 inflammasomes produces cleaved caspase-1, which cleaves both pro-IL-1β and pro-IL-18 into their biologically active mature pro-inflammatory cytokines that are released into the extracellular environment. This review will describe the molecular structure, cellular signaling pathways and current evidence for inflammasome activation following cerebral ischemia, and the potential for future treatments for stroke that may involve targeting inflammasome formation or its products in the ischemic brain.     

Variation of quality of colonoscopy in Italy over five years: A nation-wide observational study

Background/aimA nation-wide survey of colonoscopy practice carried out in 2004 showed disappointing data on colonoscopy quality in Italy. Present study was aimed prospectively at re-evaluating quality indicators of colonoscopy and their changes over a five-year-period.MethodsThe main features of each Endoscopy Unit and performance indicators on consecutive colonoscopies performed in a 2-week period were recorded. Variation of colonoscopy quality was assessed by comparing caecal-intubation and polyp-detection rates in present survey with those collected five-years before; statistical analysis was restricted to centres participating in both data collections.Results6158 colonoscopies from 116 centres were evaluated; unadjusted caecal-intubation rate was 83.0%, with 21.6% centres reporting a value >90%; mean polyp-detection rate was 32.0% (range 9.6–71.2% across centres). To assess variation of performance indicators, 4452 procedures from 77 centres were compared to 3589 procedures performed five-years before, in the same centres. A significant difference between the two rounds of data collections was observed for both caecal-intubation (82.6% versus 80.9%, p = 0.043) and polyp-detection (31.3% versus 28.1%, p = 0.002). However, 52 centres maintained a caecal-intubation rate constantly <90%.ConclusionsPresent data show that colonoscopy in Italy is still far below quality standards and that a significant improvement of practice did not occur over the last five years. Strategies to enhance colonoscopy quality should be pursued by professional societies.     

Affective temperaments: Unique constructs or dimensions of normal personality by another name?

Background

Current models theorize that affective temperaments underlie the development and expression of mood psychopathology. Recent studies support the construct validity of affective temperaments in clinical and non-clinical samples. However, one concern is that affective temperaments may be describing characteristics that are better captured by models of normal personality. We conducted two studies examining: (a) the association of affective temperaments with domains and facets of normal personality, and (b) whether affective temperaments accounted for variance in mood symptoms and disorders, impairment, and daily-life experiences over-and-above variance accounted for by normal personality.

Methods

Study 1 included 522 young adults who completed the TEMPS-A and the NEO-PI-3. Study 2 included 145 participants who were administered the TEMPS-A, NEO-FFI, interviews assessing psychopathology and impairment, and an assessment of daily life experiences.

Results

Study 1 revealed that personality domains and facets accounted for one-third to one-half of the variance in affective temperaments. However, study 2 demonstrated that affective temperaments accounted for unique variance in measures of psychopathology, impairment, and daily-life experiences after partialling variance associated with personality domains. Specifically, cyclothymic/irritable temperament predicted bipolar disorders, impairment, borderline personality traits, urgency, and anger in daily life. Hyperthymic temperament predicted hypomanic episodes, grandiosity, sensation seeking, and increased activity in daily life.

Limitations

The study was limited by the fact that only domain, not facet-level, measures of FFM were available in study 2.

Conclusions

The findings support the validity of hyperthymic and cyclothymic/irritable temperaments as indicators of clinical psychopathology and indicate that they provide information beyond normal personality.