Prenatal exposure to maternal bereavement and offspring psoriasis: a Danish nationwide cohort study.

BACKGROUND: Prenatal stress may alter immune competence of the fetus. Limited data exist on the role of antenatal stress in psoriasis development. OBJECTIVES: To investigate whether prenatal exposure to maternal bereavement increases the risk of offspring psoriasis. METHODS: This register-based cohort study included 1 811 917 live singletons born from 1978 to 2008 in Denmark. The children were assigned to the bereaved group if their mothers lost a child, partner/spouse, parent or sibling during pregnancy or up to 12 months before pregnancy. Follow-up started at the date of birth and ended at the date of first hospital treatment for psoriasis or a prescription redeemed for topical vitamin D derivatives (often used to treat psoriasis), emigration, death or 31 December 2010, whichever came first. We evaluated the hazard ratio (HR) of psoriasis in bereaved children using Cox proportional hazards regressions, compared with the nonbereaved group. RESULTS: During 28 million person-years of follow-up, 7956 children were hospitalized or prescribed medications for psoriasis. By the age of 30 years, 1·54% [95% confidence interval (CI) 1·25-1·90%] of children from the bereaved group were diagnosed with psoriasis, compared with 1·34% (95% CI 1·30-1·38%) of nonbereaved children. Overall, prenatal exposure to maternal bereavement was not associated with risk of psoriasis in general (HR 1·05, 95% CI 0·91-1·20). However, children born to mothers who lost a partner/spouse or an older child had an increased risk of psoriasis (HR 1·33, 95% CI 1·02-1·73). CONCLUSIONS: Prenatal exposure to the most stressful life event may contribute to the development and/or exacerbation of psoriasis.

Delivery by caesarean section and childhood cancer: a nationwide follow-up study in three countries.

OBJECTIVE: To investigate the association between delivery by caesarean section and risk of childhood cancer. DESIGN: A population-based, follow-up study using register data from three countries. SETTING: Denmark, Sweden and Finland. POPULATION: Children born in Denmark (1973-2007), Sweden (1973-2006) and Finland (randomly selected sample of 90%, 1987-2007; n = 7,029,843). METHODS: Exposure was delivery by caesarean section and the outcome was childhood cancer diagnosis. Follow-up started from birth and ended at the first of the following dates: cancer diagnosis, death, emigration, day before 15th birthday or end of follow-up. Cox regression was used to obtain hazard ratios. MAIN OUTCOME MEASURES: Childhood cancer diagnosis. RESULTS: A total of 882,907 (12.6%) children were delivered by caesarean section. Of these, 30.3% were elective (n = 267,603), 35.9% unplanned (n = 316,536) and 33.8% had no information on planning (n = 298,768). Altogether, 11,181 children received a cancer diagnosis. No evidence of an increased risk of childhood cancer was found for children born by caesarean section (hazard ratio, 1.05; 95% confidence interval, 0.99, 1.11). No association was found for any major type of childhood cancer, or when split by the type of caesarean section (elective/unplanned). CONCLUSION: The evidence does not suggest that caesarean section is a risk factor for the overall risk of childhood cancer and possibly not for subtypes of childhood cancer either.

Preclinical evaluation of performance, safety and usability of VAX-ID®, a novel intradermal injection device.

The recent SARS-Cov2 pandemic and mpox health emergency have led to renewed interest in intradermal vaccination due to its dose sparing potential. Indeed, intradermal vaccination is particularly of interest for use in mass vaccination campaigns, pandemic preparedness programs, and/or for vaccines that are expensive or in short supply. Moreover, the rich immune network in the skin makes it an attractive target not only for prophylactic vaccination, but also for therapeutic vaccination, like immunotherapy and (dendritic) cell-based therapies. The aim of the current paper was to provide an overview of preclinical data generated with VAX-ID®, a novel intradermal drug delivery device, to allow assessing it performance, safety and usability. The device can overcome challenges seen with the Mantoux technique whereby the needle needs to be inserted under a shallow angle. Various parameters of VAX-ID® were evaluated, including dead-space volume, dose accuracy, penetration depth & liquid deposit in piglets, as well as usability by healthcare professionals. The device has shown to have a low dead volume and a high dose accuracy. Importantly, the device performed successful injections at a predefined depth into the dermis with a high safety profile as confirmed by visual and histological evaluation in piglets. Moreover, the device was rated as easy to use by healthcare professionals. The combined preclinical performance and usability findings indicate that VAX-ID® can provide reliable, standardized and accurate drug delivery in the dermal layer of the skin with a high ease of use. The device offers a solution for injection of various prophylactic as well as therapeutic vaccines.

Vitamin B12 Deficiency Among the Healthy Jordanian Adult Population: Diagnostic Levels, Symptomology and Risk Factors.

BACKGROUND: Compared to the data available for developed countries, there is a marked scarcity of information on the levels and symptomology of vitamin B12 deficiency in developing countries, particularly in the Middle Eastern region. OBJECTIVE: To explore (a) the risk factors associated with a deficiency of vitamin B12, and (b) the baseline (cut-off) serum level of vitamin B12 for a clinically-symptomatic deficiency in the Jordanian adult population. METHODS: A total of 485 subjects were included in this study. Blood samples were drawn for biochemical analysis and data regarding socio-demographics, general health, anthropometric measures, and past medical, surgical, and medication history were collected. To explore the cut-off point, we compared all parameters included in a standard complete blood count as well as the main symptoms reported to be associated with B12 deficiency between groups of different B12 cut-off values, consisting of those above and below 200, 175, 150 and 125 pg/ml. RESULTS: Low dairy intake habits, age, recurrent headaches, heartburn, and peptic ulcer disease were found to be significantly associated with lower vitamin B12 levels. Surprisingly, daily smoking was associated with significantly higher B12 levels. The results revealed that none of the included potential indicators of B12 deficiency could be considered an indicative feature of deficiency. There were no significant differences neither in the symptoms nor in the CBC parameters between any of the tested study groups. CONCLUSION: Low dairy intake, older ages, recurrent headaches, heartburn, and peptic ulcer disease all could be considered as risk factors of having low vitamin B12 levels within the Jordanians. Also, they tend to have lower levels of vitamin B12 levels, in comparison to countries in the West, without necessarily having deficiency symptoms. The cut-off value to diagnose functional B12 deficiency could be less than 125 pg/ml for the Jordanians. More local studies are needed to establish an accurate vitamin B12 cut-off value for the population in Jordan.

The cost of mental disorders: a systematic review.

AIMS: To identify and synthesise the literature on the cost of mental disorders. METHODS: Systematic literature searches were conducted in the databases PubMed, EMBASE, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to January 1980-May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses; (2) diagnosis of at least one mental disorder; (3) study population based on the general population; (4) outcome in monetary units. The systematic review was preregistered on PROSPERO (ID: CRD42019127783). RESULTS: In total, 13 579 potential titles and abstracts were screened and 439 full-text articles were evaluated by two independent reviewers. Of these, 112 articles were included from the systematic searches and 31 additional articles from snowball searching, resulting in 143 included articles. Data were available from 48 countries and categorised according to nine mental disorder groups. The quality of the studies varied widely and there was a lack of studies from low- and middle-income countries and for certain types of mental disorders (e.g. intellectual disabilities and eating disorders). Our study showed that certain groups of mental disorders are more costly than others and that these rankings are relatively stable between countries. An interactive data visualisation site can be found here: https://nbepi.com/econ. CONCLUSIONS: This is the first study to provide a comprehensive overview of the cost of mental disorders worldwide.

Comorbidity within mental disorders: a comprehensive analysis based on 145 990 survey respondents from 27 countries.

AIMS: Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys. METHODS: The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women. RESULTS: Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2-110.8, interquartile range = 6.0-19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1-2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs. CONCLUSIONS: Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.

Diagnostic value of determination of acid and alkaline phosphatase levels in the seminal plasma of infertile males.

To investigate the diagnostic value of phosphatases in seminal plasma, the levels of acid phosphatase and alkaline phosphatase were determined in 15 fertile subjects as well as in 26 cases of oligoasthenozoospermia. Statistical analysis of obtained data showed that acid phosphatase is a reliable parameter of prostatic function in cases of infection, while alkaline phosphatase may prove to be a non-specific parameter of subfertile semen. Alkaline phosphatase was significantly diminished in both oligozoospermia and azoospermia with and without infection or varicocele.