Prescription opioids and economic hardship in France.

This paper studies how opioid analgesic sales are empirically related to socioeconomic disparities in France, with a focus on poverty. This analysis is made possible using the OpenHealth database, which provides retail sales data for opioid analgesics available on the French market. We exploit firm-level data for each of the 94 departments in Metropolitan France between 2008 and 2017. We show that increases in the poverty rate are associated with increases in sales: a one percentage point increase in poverty is associated with approximately a 5% increase in mild opioid sales. Our analysis further shows that opioid sales are positively related to the share of middle-aged people and individuals with basic education only, while they are negatively related to population density. The granularity and longitudinal nature of these data allow us to control for a large pool of potential confounding factors. Our results suggest that additional interventions should be more intensively addressed toward the most deprived areas. We conclude that a combination of policies aimed at improving economic prospects and strictly monitoring access to opioid medications would be beneficial for reducing opioid-related harm.

COVID-19 and the role of inequality in French regional departments.

In this paper, we examine the variation in the outbreak of COVID-19 across departments in continental France. We use information on the cumulated number of deaths, discharged patients and infections from COVID-19 at the department level, and study how these relate to income inequality, controlling for other factors. We find that unfortunately, inequality kills: departments with higher income inequality face more deaths, more discharged (gravely ill) patients and more infections. While other papers have studied the impact of the level of income on the severity of COVID-19, we find that it is in fact the dispersion across incomes within the same department that drives the results. Our results suggest that individuals in relatively more precarious conditions deserve dedicated policies, to avoid that temporary shocks such as COVID-19 lead to permanent increases in inequality.

DNA fragmentation in brighter sperm predicts male fertility independently from age and semen parameters.

OBJECTIVE: To evaluate whether sperm DNA fragmentation (sDF), measured in brighter, dimmer, and total populations, predicts natural conception, and to evaluate the intra-individual variability of sDF. DESIGN: Prospective study. SETTING: Outpatient clinic and diagnostic laboratory. PATIENT(S): A total of 348 unselected patients and 86 proven fertile men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): sDF was revealed with the use of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)/propidium iodide (PI). Receiver operating characteristic (ROC) curves were built before and after matching fertile men to patients for age (76:152) or semen parameters (68:136) or both (49:98). Intra-individual variability of sDF was assessed over 2 years. RESULT(S): Brighter (area under ROC curve [AUC] 0.718 ± 0.54), dimmer (AUC 0.655 ± 0.63), and total (AUC 0.757 ± 0.54) sDF predict male fertility in unmatched and age- or semen parameters-matched subjects. After matching for both age and semen parameters, only brighter (AUC 0.711 ± 0.83) and total (AUC 0.675 ± 0.92) sDF predict male fertility. At high values of total sDF, brighter predicts natural conception better than total sDF. Intra-individual coefficients of variation of sDF were 9.2 ± 8.6% (n = 25), 12.9 ± 12.7% (n = 53), and 14.0 ± 12.6% (n = 70) over, respectively, 100-day and 1- and 2-year periods, appearing to be the most stable of the evaluated semen parameters. CONCLUSION(S): The predictive power of total sDF partially depends on age and semen parameters, whereas brighter sDF independently predicts natural conception. Therefore, brighter sDF is a fraction of sDF that adds new information to the routine semen analysis. At high levels of sDF, distinguishing the two sperm populations improves the predictive power of sDF. Overall, our results support the idea that TUNEL/PI can be of clinical usefulness in the male fertility workup.

Acrosome reaction is impaired in spermatozoa of obese men: a preliminary study.

OBJECTIVE: To compare spontaneous (Sp-AR) and P-induced acrosome reaction (AR) in spermatozoa of obese and lean subjects. SETTING: Bariatric unit at a university hospital. DESIGN: Prospective, observational study. PATIENT(S): Twenty-three obese (mean±SD body mass index [BMI], 44.3±5.9 kg/m2) and 25 age-matched lean (BMI, 24.2±3.0 kg/m2) subjects. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Spontaneous and P-induced AR in spermatozoa of obese and lean subjects. RESULT(S): A statistically significant difference was found between obese and lean cohorts in total T and calculated free T, E2, glycated hemoglobin, and high-density lipoproteins, whereas among the routine semen parameters analyzed, only immotile sperm percentage and ejaculate volume differed significantly. Spermatozoa of obese (n=13) vs. lean men (n=19) showed a higher Sp-AR (17.9%±7.2% vs. 8.3%±4.2%), which resulted in a reduced ability to respond to P evaluated as the AR-after-P-challenge parameter (3.5%±3.2% vs. 17.6%±9.2%). Multivariate analysis adjusted for age revealed a significant correlation between BMI, waist, E2, and glycated hemoglobin with both Sp-AR (age-adjusted r=0.654, r=0.711, r=0.369, and r=0.644, respectively) and AR-after-P-challenge (age-adjusted r=-0.570, r=-0.635, r=-0.507, and r=-0.563, respectively). A significant difference in sperm cholesterol content was reported between obese and lean men (29.8±19.5 vs. 19.1±14.6 ng/µg of proteins). CONCLUSION(S): Sperm AR is impaired in obese men, showing reduced response to P and elevated Sp-AR, associated with altered circulating levels of E2 and sperm cholesterol content.

Scoring human sperm morphology using Testsimplets and Diff-Quik slides.

OBJECTIVE: To compare two staining methods to assess sperm morphology: Diff-Quik (DQ), which is the fastest of the recommended techniques, and Testsimplets (TS), a technique that uses prestained slides and is quite popular in in vitro fertilization (IVF) centers. DESIGN: Prospective study. SETTING: Patients at the Sterility Center of the Obstetrics and Gynecology Unit of the Hospital of S.S. Cosma and Damiano (Azienda USL 3 of Pistoia, Italy). PATIENT(S): 104 randomly enrolled male patients evaluated by the seminology laboratory. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Statistical comparison of sperm morphology results obtained after staining of semen samples both with DQ and TS. RESULT(S): Our data show that TS gives a statistically significantly lower number of normal forms than DQ (median: 6% [range: 0-29%] vs. 12% [range: 0-40%], respectively) as well as an overestimation of sperm head defects (median: 92.0% [range: 67%-100%] vs. 82.3% [range: 55%-100%], respectively). CONCLUSION(S): The two staining methods should not be considered equivalent. Specifically, the lower reference limit established by the World Health Organization is not appropriate when sperm morphology is assessed by TS. The routine application of TS in the evaluation of sperm morphology is therefore not recommended because it leads to an overestimation of patients with sperm morphology values below the lower reference limit (4%), thus potentially influencing clinical decisions.

Mechanisms and clinical correlates of sperm DNA damage.

Among the different DNA anomalies that can be present in the male gamete, DNA fragmentation is the most frequent, particularly in infertile subjects. There is now consistent evidence that a sperm containing fragmented DNA can be alive, motile, morphologically normal and able to fertilize an oocyte. There is also evidence that the oocyte is able to repair DNA damage; however, the extent of this repair depends on the type of DNA damage present in the sperm, as well as on the quality of the oocyte. Thus, it is important to understand the possible consequences of sperm DNA fragmentation (SDF) for embryo development, implantation, pregnancy outcome and the health of progeny conceived, both naturally and by assisted reproductive technology (ART). At present, data on the consequences of SDF for reproduction are scarce and, in many ways, inconsistent. The differences in study conclusions might result from the different methods used to detect SDF, the study design and the inclusion criteria. Consequently, it is difficult to decide whether SDF testing should be carried out in fertility assessment and ART. It is clear that there is an urgent need for the standardisation of the methods and for additional clinical studies on the impact of SDF on ART outcomes.