Association of COVID-19 mortality with COVID-19 vaccination rates in Rhineland-Palatinate (Germany) from calendar week 1 to 20 in the year 2021: a registry-based analysis

Vaccination is among the measures implemented by authorities to control the spread of the COVID-19 pandemic. However, real-world evidence of population-level effects of vaccination campaigns against COVID-19 are required to confirm that positive results from clinical trials translate into positive public health outcomes. Since the age group 80?+?years is most at risk for severe COVID-19 disease progression, this group was prioritized during vaccine rollout in Germany. Based on comprehensive vaccination data from the German federal state of Rhineland-Palatinate for calendar week 1–20 in the year 2021, we calculated sex- and age-specific vaccination coverage. Furthermore, we calculated the proportion of weekly COVID-19 fatalities and reported SARS-CoV-2 infections formed by each age group. Vaccination coverage in the age group 80?+?years increased to a level of 80% (men) and 75% (women). Increasing vaccination coverage coincided with a reduction in the age group’s proportion of COVID-19 fatalities. In multivariable logistic regression, vaccination coverage was associated both with a reduction in an age-group’s proportion of COVID-19 fatalities [odds ratio (OR) per 5 percentage points?=?0.89, 95% confidence interval (CI)?=?0.82–0.96, p?=?0.0013] and of reported SARS-CoV-2 infections (OR per 5 percentage points?=?0.82, 95% CI 0.76–0.88, p?<?0.0001). The results are consistent with a protective effect afforded by the vaccination campaign against severe COVID-19 disease in the oldest age group.

     

Maternal Environmental Exposure, Infant GSTP1 Polymorphism, and Risk of Isolated Congenital Heart Disease

The GSTP1 gene, highly expressed early in fetal life, is the most abundant phase 2 xenobiotic metabolism enzyme in a human placenta. Fetal inherited GSTP1 Ile105Val polymorphism may modify the metabolism and excretion of xenobiotics from fetal tissue and increase the risk of congenital heart disease (CHD). This study aimed to analyze the joint effects of GSTP1 genetic polymorphism (Ile105Val) and maternal environmental exposure on CHD risk. Within a case-control design, a total of 190 children with CHD (104 boys age 4 ± 5.6 years) and 190 healthy children (114 newborn boys) were genotyped for the GSTP1 Ile105Val polymorphism. Mothers completed a structured questionnaire on the demographics as well as the preconceptional and lifestyle exposures. A higher frequency of mothers of children with CHD (38 %) reported a positive history of exposure to toxicants (occupational and environmental) than mothers of healthy children (23 %) (p = 0.0013). Logistic regression analysis showed that maternal occupational and environmental exposures increased the risk of CHD (odds ratio, 2.6; 95 % confidence interval, 1.6–4.2; p < 0.0001). No significant differences in Ile105Val genotype frequencies were observed between the children with CHD and the healthy children (p = 0.9). Furthermore, case-control analysis showed no evidence of significant interaction between the maternal exposures and GSTP1 polymorphism. Maternal exposure to toxicants increased the risk of children with CHD. However, fetal GSTP1 Ile105Val polymorphism did not increase the risk of CHD.     

Maternal and paternal environmental risk factors, metabolizing GSTM1 and GSTT1 polymorphisms, and congenital heart disease

Congenital heart defects (CHDs) are the most prevalent of all birth malformations arising from the complex interplay of environmental exposures and genes. Modifiable environmental risk factors are still largely unknown, especially for paternal exposure. The aim of the present study was to examine the association between the environmental exposures of both parents and CHD risk and to explore the modification effect of metabolizing gene polymorphisms in children who lack the genetic capacity to produce the glutathione S-transferase (GST) GSTM1 and GSTT1 enzymes. A total of 330 parents of a child with CHD and 330 parents of a child without any congenital malformations were compared in terms of lifestyle habits and toxicant exposure. GST gene polymorphisms were investigated in 180 patients with CHD (104 males, age 4.9 ± 5.8 years). Paternal smoking (≥15 cigarettes/day) was significantly associated with CHD risk (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.5, p = 0.002). Both maternal (OR 2.6, 95% CI 1.6 to 4.2, p <0.0001) and paternal (OR 2.5, 95% CI 1.6 to 3.8, p <0.0001) occupational/environmental exposures increased the risk of CHD. Also, a significant additive risk (OR 4.5, 95% CI 2.5 to 8.3, p <0.0001) was found when both parents were exposed to toxicants. Both maternal (OR 3.6, 95% CI 1.1 to 11.2, p = 0.03) and paternal (OR 3.3, 95% CI 1.0 to 10.8, p = 0.03) exposure to toxicants increased the CHD risk in children who carried the combined null GST genotypes. The effect for the combined null GST genotypes was also stronger (OR 6.5, 95% CI 1.5 to 28.0) when both parents were exposed. In conclusion, paternal smoking and exposure to toxicants for both parents affect the risk of children with CHD. Polymorphisms in GST genes can modify a person's risk of toxicant exposure-induced disease.     

Fractionations in radiotherapy of brain metastases

AIMS AND BACKGROUND: The aim of this study was to evaluate different fractionations for radiotherapy of brain metastases. METHODS: One hundred and twenty-five patients treated with whole brain cobalt therapy (WBRT) were examined to evaluate the effect on survival and quality of life of three different dose fractionations (2 Gy x 25, 3 Gy x 10 and 4 Gy x 5). Fractionation was evaluated in relation to mean survival, single or multiple lesions, presence of extracranial metastases, primary tumor control and neurological status before and after treatment. Kaplan-Meier analysis of survival and univariate and multivariate analysis of these factors were performed. Twenty-six (21%) patients were treated with 2 Gy x 25, 48 patients (38%) with 3 Gy x 10 and 42 patients (33%) with 4 Gy x 5. The other 9 patients were treated with unusual fractionations. RESULTS: In 66% of patients an improvement in neurological status after radiotherapy was recorded. Patients with controlled primary tumors had a better mean survival, 8.6 months, if they had no extracranial metastases. The six-month survival was 21% in the 4 Gy x 5 group, 36% in the 3 Gy x 10 group, and 21% in the 2 Gy x 25 group; the results for one-year actuarial survival were highly similar in the three fractionation groups (5%, 11% and 6%, respectively). CONCLUSIONS: The use of 5 x 4 Gy fractionation may be appropriate in lung cancer patients, where no significant difference in 6- and 12-month survival was observed with respect to the other fractionation groups despite the most unfavorable prognosis of these patients and the lower biological effectiveness of this fractionation with respect to the other schedules.