The temporal correlation between positive testing and death in Italy: from the first phase to the later evolution of the COVID-19 pandemic

After the global spread of the novel coronavirus disease 2019 (COVID-19), research has concentrated its efforts on several aspects of the epidemiological burden of pandemic. In this frame, the presented study follows a previous analysis of the temporal link between cases and deaths during the first epidemic wave (Phase 1) in Italy (March-June 2020). We here analyze the COVID-19 epidemic in the time span from March 2020 to June 2021. The elaboration of the curves of cases and deaths allows identifying the temporal shift between the positive testing and the fatal event, which corresponds to one week from W2 to W33, two weeks from W34 to W41, and three weeks from W42 to W67. Based on this finding, we calculate the Weekly Lethality Rate (WLR). The WLR was grossly overestimated (~13.5%) in Phase 1, while a mean value of 2.6% was observed in most of Phase 2 (starting from October 2020), with a drop to 1.4% in the last investigated weeks. Overall, these findings offer an interesting insight into the magnitude and time evolution of the lethality burden attributable to COVID-19 during the entire pandemic period in Italy. In particular, the analysis highlighted the impact of the effectiveness of public health and social measures, of changes in disease management, and of preventive strategies over time.

Magnitude and time-course of excess mortality during COVID-19 outbreak: population-based empirical evidence from highly impacted provinces in northern Italy

BackgroundThe real impact of SARS-CoV-2 on overall mortality remains uncertain and surveillance reports attributed to COVID-19 a limited amount of deaths during the outbreak. Aim of this study is to assess the excess mortality (EM) during COVID-19 outbreak in highly impacted areas of northern Italy. MethodsWe analyzed data on deaths occurred in the first four months of 2020 in health protection agencies (HPA) of Bergamo and Brescia (Lombardy), building a time-series of daily number of deaths and predicting the daily standardized mortality ratio (SMR) and cumulative number of excess deaths (ED) through a Poisson generalized additive model of the observed counts in 2020, using 2019 data as a reference. ResultsWe estimated 5740 (95% Credible Set (CS): 5552-5936) ED in the HPA of Bergamo and 3703 (95% CS: 3535 - 3877) in Brescia, corresponding to 2.55 (95% CS: 2.50-2.61) and 1.93 (95% CS: 1.89-1.98) folds increase in the number of deaths. The ED wave started a few days later in Brescia, but the daily estimated SMR peaked at the end of March in both HPAs, roughly two weeks after the introduction of lock-down measures, with significantly higher estimates in Bergamo (9.4, 95% CI: 9.1-9.7). ConclusionEM was significantly larger than that officially attributed to COVID-19, disclosing its hidden burden likely due to indirect effects on health system. Time-series analyses highlighted the impact of lockdown restrictions, with a lower EM in the HPA where there was a smaller delay between the epidemic outbreak and their enforcement.

Delayed puberty versus hypogonadism: a challenge for the pediatrician

Constitutional delay of growth and puberty (CDGP) is the most common cause of delayed puberty (DP), is mainly found in males, and is characterized by short stature and delayed skeletal maturation. A family history of the subject comprising the timing of puberty in the parents and physical examination may provide clues regarding the cause of DP. Delayed onset of puberty is rarely considered a disease in either sex. In fact, DP usually represents a common normal variant in pubertal timing, with favorable outcomes for final height and future reproductive capacity. In adolescents with CDGP, a linear growth delay occurs until immediately before the start of puberty, then the growth rate rapidly increases. Bone age is often delayed. CDGP is a diagnosis of exclusion; therefore, alternative causes of DP should be considered. Functional hypogonadotropic hypogonadism may be observed in patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions including celiac disease, inflammatory bowel diseases, kidney insufficiency, and anorexia nervosa. Permanent hypogonadotropic hypogonadism (pHH) showing low serum value of testosterone or estradiol and blunted follicle-stimulating hormones (FSH) and luteinizing hormones (LH) levels may be due to abnormalities in the central nervous system. Therefore, magnetic resonance imaging is necessary to exclude morphological abnormalities and neoplasia. Moreover, pHH may be isolated, as observed in Kallmann syndrome, or associated with other hormone deficiencies, as found in panhypopituitarism. Baseline or gonadotropin-releasing hormone pituitary stimulated gonadotropin level is not sufficient to easily differentiate CDGP from pHH. Low serum testosterone in male patients and low estradiol values in female patients, associated with high serum FSH and LH levels, suggest a diagnosis of hypergonadotropic hypogonadism. A genetic analysis can reveal a chromosomal abnormality (e.g., Turner syndrome or Klinefelter syndrome). In cases where the adolescent with CDGP is experiencing psychological difficulties, treatment should be recommended.

A Possible Pathogenic Linkage Among Headache, Migraine, and Nocturnal Enuresis in Children / 대한배뇨장애요실금학회지

PURPOSE: This study aims to evaluate the prevalence of headaches and migraine in children with nocturnal enuresis (NE) and to improve knowledge on these conditions. In particular, for this purpose, a possible pathogenic relationship linking both conditions and the impact of headaches and migraine on NE persistence was evaluated. METHODS: Researchers enrolled 123 children with NE, aged between 5 and 15 years, referred to the Service of Pediatrics, Campus Bio-Medico University Hospital of Rome between January 2014 and January 2015. Parents of all children enrolled in the study were invited to complete a self-reported questionnaire. The study protocol was approved by the Human Research Ethics Committee of Campus-Bio-Medico University. The NE group data was compared with the data of a control group (107 children). RESULTS: Of the eligible patients, 7.8% suffer from headaches/migraine (mean age, 9.63 years; interquartile range [IQR], 3.5 years) and 47.1% have a family history of headaches (mean age, 8.46 years; IQR, 3.75 years). Of the 8 patients with headaches, all are male, 3 have tension-type headaches (2 of them have maternal family history) and 5 have migraine (3 of them have maternal family history). Of the 35.3% with a migraine family history (mean age, 8.36 years; IQR, 3.5 years), 22 are male, and 14 are female. Three of these patients have migraine. A total of 92.2% suffer from NE but not from headaches (mean age, 8.43 years; IQR, 3 years). Of these patients, 33 are female (35.1%), and 61 are male (64.9%). In the control group, 4.7% (5 out of 107) of the children suffer from headaches, and of these, 4 are affected by nonmigraine headaches and 1 by migraine. CONCLUSIONS: In conclusion, according to the hypothesis, NE and headaches/migraine could be linked by several similarities.

Melatonin's Effect on the Efficacy of Desmopressin in the Treatment of Enuresis / 대한배뇨장애요실금학회지

PURPOSE: This study aims to evaluate and compare the efficacy of exogenous melatonin associated with desmopressin (dDAVP) and dietary recommendations. METHODS: A total of 189 patients were enrolled from the Service of Pediatrics, Campus Bio-Medico University Hospital of Rome, from January 2013 to June 2015. Of the 189 original patients, 153 children, aged between 5 and 14 years (mean age, 8.7 years) were included in the study. After clinical evaluation and a 3-month period of observation without treatment, children were assigned to receive treatment in one of 3 groups: group 1, dDAVP at a dose of 120 mcg a day (Minirin); group 2, dDAVP at a dose of 120 mcg and dietary recommendations; or group 3, dDAVP at a dose of 120 mcg, dietary recommendations, and melatonin at a dose of 1 mg a day (Melamil plus). Each patient was treated for 3 months. RESULTS: After the 3 months of therapy, a desiderable response was achieved in 30 of 51 patients (58.82%) treated with dDAVP, 35 of 53 patients (66.04%) treated with dDAVP and dietary recommendations, and 35 of 49 patients (71.43%) treated with dDAVP, dietary recommendations, and melatonin. CONCLUSIONS: Although not statistically significant, the results show that the association between dDAVP treatment with dietary recommendations and melatonin could be considered a safe and effective treatment of NE. Considering that the statistically insignificant results might be due to the small sample size, the study will be continued to increase the number of subjects.