The human factor: does the operator performing the embryo transfer significantly impact the cycle outcome?

STUDY QUESTION: Is Ongoing Pregnancy Rate (OPR) operator-dependent, and can experience improve embryo transfer efficiency? SUMMARY ANSWER: OPR is influenced by the operators who perform the embryo transfer (ET), and experience does not assure proficiency for everyone. WHAT IS KNOWN ALREADY: ET remains the critical step in assisted reproduction. Although many other factors such as embryo quality and uterine receptivity impact embryo implantation, the proper ET technique is clearly an operator-dependent variable and as such it should be objectively standardized. STUDY DESIGN, SIZE, DURATION: Retrospective comparative analysis including all fresh ETs performed between January 1996 and December 2016 at the Humanitas Fertility Center after IVF-ICSI cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: IVF/ICSI fresh ETs performed by 32 operators, 19 824 cycles in all, were analyzed. All transfers consisting of freehand insertion of a preloaded soft catheter into the uterine cavity under transabdominal ultrasound guidance were considered. Two different statistical analyses were performed. First, a logistic regression model with a random intercept for the operator was used to estimate the heterogeneity of the rate of success among operators, accounting for woman age, FSH, number of oocytes retrieved, fertilization rate, year of the procedure, number and stage of transferred embryos and operator's experience. Second, the relationship between experience and pregnancy rate was estimated separately for each operator by logistic regression, and operator-specific results were combined and compared in a random-effects meta-analysis. In both analyses, the operator's experience at time t was measured in terms of number of embryo transfers performed before t. MAIN RESULTS AND THE ROLE OF CHANCE: The heterogeneity among operators was highly significant (P value <0.001) and explained 44.5% of the total variability. The odds ratio of success of the worst operator in respect to the mean was equal to 0.84. For the best operator, the odds ratio of success was equal to 1.13 in respect to the mean. Based on the meta-analysis of the relationship between operator's experience and success rate, it resulted that, on average, the operators' performance did not improve with additional transfers. LIMITATIONS, REASONS FOR CAUTION: At our center, operators become independent for ET's after performing between 30 and 50 transfers under supervision. It is also possible that other relevant factors, such as embryologists on duty for the ET, have not been included in the present analysis and this may represent a potential bias. Among these, it should be mentioned that the embryologists on duty for the ET were not taken into consideration. WIDER IMPLICATIONS OF THE FINDINGS: Continued performance analysis and the use of a digital simulator could help operators to test their expertise over time and either correct poor performance or avoid doing transfers. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: NCT03561129.

Fine airborne particles: when alarming levels are the standard.

OBJECTIVES: To quantify the contribution of each individual month to the annual mortality burden attributable to particulate matter (PM) in 2015 in Milan, Italy, after authorities and media considered December 2015 as an outlying month carrying an exceptional population exposure to PM. STUDY DESIGN: We used routinely available daily time series of air pollution and mortality to perform an assessment of the impact of PM exposure on population health. METHODS: By combining daily death counts with daily PM levels, as well as the yearly average of the number of deaths with the yearly average of PM concentrations, impact estimates were calculated in terms of deaths attributable (AD) to levels of PM10 and PM2.5 exceeding the daily or the annual European Union (EU) exposure limits. RESULTS: On a monthly basis, the estimated AD for exceeding the daily EU limits for more than 35 days were 18.4 (PM10) and 33.2 (PM2.5) between January and March, and 20.0 and 31.9 between October and December, respectively. On an annual basis, the EU limit for PM10 was almost met and, therefore, the estimated impact in terms of AD was practically null. CONCLUSIONS: Impact results should be interpreted in the light of the skewness of the daily PM concentration distribution. The number of days above the limits is more important than the average annual concentration in determining the number of attributable deaths. The impact of PM on mortality is substantial during the whole winter season irrespective of its annual average concentration. Our estimates further stress the need for a revision of the current European air quality standards.

Impact of hand and face disabilities on global disability and quality of life in systemic sclerosis patients.

OBJECTIVES: In systemic sclerosis (SSc), the frequent involvement of hand and face leads to their disability. We aimed to assess influence of hand and face disability on global disability and Health related Quality of life (HRQoL). METHODS: 119 SSc patients were assessed for global disability by HAQ, HRQoL, by SF36; hand disability by HAMIS, CHFDS, fist closure and hand opening measures; face disability by MHISS and mouth opening measure. RESULTS: Diffuse SSc (dSSc) patients present higher HAQ, lower Summary Physical Index (SPI) of SF36, major hand disability at hand (higher HAMIS, CHFDS, fist closure, lower hand opening) and face (lower mouth opening, higher MHISS) than lSSc patients (p<0.05). SPI of SF36 is negatively correlated with MHISS, CHFDS, HAMIS and positively correlated to mouth and hand opening (p<0.05). Summary Mental Index (SMI) of SF36 is negatively correlated with MHISS (p<0.05). HAQ is negatively correlated with mouth opening and positively correlated to MHISS, HAMIS, CHFDS (p<0.05). By hierarchical multiple linear regression, SPI of SF36 is significantly associated with total MHISS (B=-0.34; t=-3.78; p<0.001) and CHFDS (B=-0.27; t=-3.01; p=0.003), together, explaining 22% of SPI variance. SMI of SF36 is significantly associated only with MHISS total score (B=-0.22; t=-2.41; p=0.017), explaining 4% of its variance. HAQ is significantly associated with CHFDS score (B=0.61; t=7.90; p<0.001), explaining 36% of HAQ variance. CONCLUSIONS: dSSc patients present higher global and local disability, and lower HRQoL in SPI than lSSc patients. Local disabilities, assessed by CHDFS and MHISS, are independently related to global disability and HRQoL.

The effect of a combined rehabilitation program on the temporomandibular joint in systemic sclerosis evaluated by ultrasound exam.

PURPOSE: Temporomandibular joint (TMJ) involvement is frequent in Systemic Sclerosis (SSc). Dysfunction and X-ray changes of TMJ were described only in few observational studies. Treatment as well has been seldom considered. Aim of the present study was to evaluate the effects on TMJ of two specifically designed physiotherapy protocols. METHODS: The study group included 26 SSc outpatients (22 females and 4 males with mean age ± SD 59.08 ± 10.31 years). Thirteen patients were randomly assigned to a treatment (protocol 1) including home exercises for TMJ and thirteen to a treatment (protocol 2) including home exercises and a combined procedure. The rehabilitation effects on the TMJ were evaluated by ultrasound examination (UE) in static and dynamic phases. UE was performed in all patients before and at the end of the treatment and after a follow up (8 weeks). RESULTS: Both rehabilitation protocols induced a significant improvement (protocol 1: p < 0.01 and protocol 2: p < 0.005) of mouth opening with a long-lasting effect. Protocol 2 was more effective than protocol 1. A significant increase of bilateral condyle-head temporal bone distance was detected by UE at the end of both treatments. It was maintained at follow-up in patients treated with Protocol 2. CONCLUSIONS: The present investigation shows that a rehabilitation program characterized by home exercises with a combined procedure is useful to recover the function of TMJ. The data also show that UE is helpful in the evaluation of TMJ in SSc and in the assessment of the efficacy of the rehabilitation programs.

Efficacy of a tailored rehabilitation program for systemic sclerosis.

INTRODUCTION: Rehabilitation may contribute to the management of Systemic Sclerosis (SSc) dealing with disabilities due to skin and joint involvement. AIM: to evaluate the efficacy of a district specific and global rehabilitation program tailored for SSc patients. MATERIALS AND METHODS: 20 SSc patients were enrolled and randomly assigned to 2 groups. Interventional group (10 pts) was treated that included hand and face specific rehabilitation and at least a global rehabilitation technique such as hydrokinesytherapy or land-based program, also comprising respiratory exercises. Hand lymphatic drainage was added when necessary. Observational group (10 patients) was only provided with educational advices and medical information about SSc. Patients were evaluated at baseline (T0) and after the 9 weeks treatment period (T1). Interventional group was also assessed after a 9 weeks follow-up (T2). Patients were evaluated by SF-36, HAQ and a purpose-built-questionnaire for global health condition and with Hamis test, Duruöz scale, range of motion, water volumetric test, mouth opening and a purpose-built-questionnaire for hand and face involvement. RESULTS: At the end of the treatment, patients of interventional group improved in all the parameters evaluated. At follow-up, mouth mobility and functionality such as global health status was partially lost, only hand mobility and functionality parameters were maintained. No changes were observed in controls. CONCLUSION: The association and of district-specific and global rehabilitative techniques conceived and tailored for SSc patients improves disability, HRQoL, hand and face disability and functionality, with its effects partially maintained at the follow-up.

Effects of cold weather on mortality: results from 15 European cities within the PHEWE project.

Weather-related health effects have attracted renewed interest because of the observed and predicted climate change. The authors studied the short-term effects of cold weather on mortality in 15 European cities. The effects of minimum apparent temperature on cause- and age-specific daily mortality were assessed for the cold season (October-March) by using data from 1990-2000. For city-specific analysis, the authors used Poisson regression and distributed lag models, controlling for potential confounders. Meta-regression models summarized the results and explored heterogeneity. A 1 degrees C decrease in temperature was associated with a 1.35% (95% confidence interval (CI): 1.16, 1.53) increase in the daily number of total natural deaths and a 1.72% (95% CI: 1.44, 2.01), 3.30% (95% CI: 2.61, 3.99), and 1.25% (95% CI: 0.77, 1.73) increase in cardiovascular, respiratory, and cerebrovascular deaths, respectively. The increase was greater for the older age groups. The cold effect was found to be greater in warmer (southern) cities and persisted up to 23 days, with no evidence of mortality displacement. Cold-related mortality is an important public health problem across Europe. It should not be underestimated by public health authorities because of the recent focus on heat-wave episodes.

Impact of heat on mortality in 15 European cities: attributable deaths under different weather scenarios.

BACKGROUND: High ambient summer temperatures have been shown to influence daily mortality in cities across Europe. Quantification of the population mortality burden attributable to heat is crucial to the development of adaptive approaches. The impact of summer heat on mortality for 15 European cities during the 1990s was evaluated, under hypothetical temperature scenarios warmer and cooler than the mean and under future scenarios derived from the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios (SRES). METHODS: A Monte Carlo approach was used to estimate the number of deaths attributable to heat for each city. These estimates rely on the results of a Bayesian random-effects meta-analysis that combines city-specific heat-mortality functions. RESULTS: The number of heat-attributable deaths per summer ranged from 0 in Dublin to 423 in Paris. The mean attributable fraction of deaths was around 2%. The highest impact was in three Mediterranean cities (Barcelona, Rome and Valencia) and in two continental cities (Paris and Budapest). The largest impact was on persons over 75 years; however, in some cities, important proportions of heat-attributable deaths were also found for younger adults. Heat-attributable deaths markedly increased under warming scenarios. The impact under SRES scenarios was slightly lower or comparable to the impact during the observed hottest year. CONCLUSIONS: Current high summer ambient temperatures have an important impact on European population health. This impact is expected to increase in the future, according to the projected increase of mean ambient temperatures and frequency, intensity and duration of heat waves.

NuGO PPS1 mouse study 1: preliminary statistical analysis.

Time course experiments are aimed at characterizing the dynamic regulation of gene expression in biological systems. Data are collected at different time points to monitor the dynamic behaviour of gene expression. The NuGO PPS Mouse Study 1 investigates the development of high fat-induced insulin resistance (IR) over time in APOE*3Leiden (E3L) mice. The study consists in a series of analyses at time points, which are crucial in the development of central and peripheral IR. Affymetrix arrays have been made on critical organs. We present the results of the preliminary statistical analysis on these microarray data. We used a non-parametric approach to identify genes the expression of which changed over time, separately for three tissues: liver, muscle and white adipose tissue. We specified for each gene a basic ANOVA model, in order to check the null hypothesis that gene expression did not vary over time. We addressed the multiple tests problem calculating positive false discovery rate and q values for the F test statistics. The appropriateness of the hypothesis of homogeneous variances over time was investigated by mean of the Bartlett's test for homoschedasticity. This is a relevant point because heteroschedasticity could be indicative of outlying behaviour of some individuals at specific time points. The necessity to use a moderated F test was evaluated. We found that a considerable part of the genes varied expression over time. For part of the genes, the variance of the response was not homogeneous over time. Response differed by tissue.

Viewing less to see better.

OBJECTIVE: To assess the efficacy, as well as the long term duration, of a new procedure for the rehabilitation of visuospatial neglect in patients with right hemisphere stroke. METHODS: Patients with right unilateral hemispheric damage identified with neglect were assigned to a treatment (T+) or a control (T-) group. The treatment consisted in abolishing all visual inputs from the right hemispace for one week by means of specially devised hemiblinding goggles. Patients' visuospatial abilities were tested and compared between groups immediately after the week of treatment. Both groups were further assessed one week after treatment suspension for evaluation of long term beneficial effects. RESULTS: Following the treatment, a substantial amelioration of visuospatial neglect symptoms was selectively observed in the T+ group. In contrast, untreated patients showed only weak signs of recovery. Most important, the amelioration obtained in the T+ group of patients was not ephemeral, being significantly maintained after a further period of one week, even after suspension of the treatment. CONCLUSION: The protracted efficacy of the proposed "hemiblinding technique" may have important implications for the recovery of visuospatial neglect and may be a very promising tool for investigating both the cognitive and the neural basis of neglect rehabilitation.

Measuring muscular strength of the lower limbs by hand-held dynamometer: a standard protocol.

The aim of this study is to describe the reliability of measuring maximal strength of eight muscle groups of the lower limb by a hand-held dynamometer, according to a standard assessment protocol. The study population consisted of 26 patients (14 males and 12 females; age range 60-90 years) admitted to a geriatric hospital. Multiple assessments of muscle strength by two different examiners were compared to estimate test-retest and inter-rater reliability. The range of strength evaluated across the eight muscle groups was 2.1-29.8 Kg/force. Overall, short-term (same day) and long-term (one week apart) test-retest and inter-rater reliability were very high, with 60% of the intraclass correlation coefficient values above 0.8, and the majority above 0.7. No significant differences in strength were found comparing the left and the right side of each muscle group. Differences between values collected in the same subject by two different examiners, and by the same examiner at different points in time were similar, not influenced by the average strength of the muscle group, and significantly larger for long-term than for short-term comparisons. By using a standardized measurement protocol, reliable measurements of muscle strength can be obtained by a hand-held dynamometer in frail older persons.

Acute effects of particulate air pollution on respiratory admissions: results from APHEA 2 project. Air Pollution and Health: a European Approach.

The APHEA 2 project investigated short-term health effects of particles in eight European cities. In each city associations between particles with an aerodynamic diameter of less than 10 microm (PM(10)) and black smoke and daily counts of emergency hospital admissions for asthma (0-14 and 15-64 yr), chronic obstructive pulmonary disease (COPD), and all-respiratory disease (65+ yr) controlling for environmental factors and temporal patterns were investigated. Summary PM(10) effect estimates (percentage change in mean number of daily admissions per 10 microg/m(3) increase) were asthma (0-14 yr) 1.2% (95% CI: 0.2, 2.3), asthma (15-64 yr) 1.1% (0.3, 1.8), and COPD plus asthma and all-respiratory (65+ yr) 1.0% (0.4, 1.5) and 0.9% (0.6, 1.3). The combined estimates for Black Smoke tended to be smaller and less precisely estimated than for PM(10). Variability in the sizes of the PM(10) effect estimates between cities was also investigated. In the 65+ groups PM(10) estimates were positively associated with annual mean concentrations of ozone in the cities. For asthma admissions (0-14 yr) a number of city-specific factors, including smoking prevalence, explained some of their variability. This study confirms that particle concentrations in European cities are positively associated with increased numbers of admissions for respiratory diseases and that some of the variation in PM(10) effect estimates between cities can be explained by city characteristics.