Clinical pharmacology of oral and intravenous 4-demethoxydaunorubicin

Summary The clinical pharmacology of 4-demethoxydaunorubicin (4-DMDNR) was studied in 28 patients with advanced breast cancer, using a sensitive reverse-phase HPLC technique. All patients had normal renal and hepatic function. The serum levels of 4-DMDNR after a single i.v. bolus injection followed a triple exponential decay curve (T1/2=9.6 min, T1/2=3.2 h and T1/2=34.7 h) and conformed to a three-compartment model. Comparison of the area under the curve (AUC) and urinary excretion for the oral and i.v routes suggests an oral bioavailability of approximately 24%. In patients treated with a schedule of weekly oral administration for periods of up to 12 months there was no significant alteration in either AUC or elimination half-life for the parent drug or its principal metabolite 13-OH4DMDNR. Moreover, there was no evidence of accumulation of the metabolite although measurable amounts were present 7 days after administration of 4-DMDNR.This work was supported by the Cancer Research Campaign and Farmitalia Carlo Erba Ltd     

A new superselective balloon catheter--all-silicone catheter with a floppy tip

We have introduced concept of "chemical" embolization and have tried to develop a new agent which would enable us to embolize the lesion with one-shot injection. Such an agent must be able to occlude diffusely the lesion distal to the catheter. This has made it mandatory to develop a new catheter which can be introduced into the vessel as close to the lesion as possible with fewer risks of clot formation and/or vessel damage. A new superselective balloon catheter for angiography and infusion of liquid embolizing materials has been developed. This catheter consists of a proximal relatively stiff silicone catheter, a short distal thin-walled flexible silicone catheter and silicone balloon. These three silicone components are connected by silicone adhesives. The distal catheter allows us to catheterize fine arteries such as lenticulostriates, while the proximal catheter assures easy manipulation. This balloon catheter can be used for superselective angiography and infusion of liquid embolizing materials. It has been used on nine patients; one with a dural arterio-venous malformation (AVM), four with meningiomas, and four with brain and spinal cord AVMs. In the case of dural AVM and meningiomas, it was possible to easily introduce into the middle meningeal artery distal to the foramen spinosum. In addition, in one of the cases of meningioma, we were able to catheterize one of the main feeding pedicles beyond the pterion. Chemical embolization was carried out in 5 cases with good results. In the case of brain and spinal cord AVM, useful information was obtained from the superselective angiography.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis of 131I, 125I and 82Br labelled (E)-5-(2-halovinyl)-2'-deoxyuridines

Radiohalogenated (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU, 4) and (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU, 5) were synthesized by reaction of (E)-5-(2-carboxyvinyl)-2'-deoxyuridine (1) with radiolabelled iodide or bromide in the presence of chloramine-T. A "no-carrier-added" synthesis of [131I]IVDU was completed within 30 min providing a radiochemical yield of 65%. Alternatively, radioactive iodine was incorporated into IVDU using a halogen isotope exchange reaction catalyzed by cuprous ion. [82Br]BVDU was also prepared by direct neutron activation of unlabelled BVDU.     

Associations between interpersonal violence victimisation and concussions among US college students

Interpersonal violence is common on college campuses and is associated with many adverse health outcomes; however, it remains unknown whether experiencing interpersonal violence victimisation is associated with concussions. The aim of this study was to estimate the associations between interpersonal violence, including emotional abuse, physical abuse and sexual assault, and concussions among a large, diverse sample of college students. We analysed cross-sectional data from the 2018–2019 national (US) Healthy Minds Study (N = 1,478). Multiple logistic regression analyses were conducted to estimate the association between interpersonal violence victimisation (any violence victimisation, emotional abuse, physical abuse and sexual assault) and concussion history (any concussion, diagnosed concussion and undiagnosed concussion), while adjusting for potential confounders. Analyses were conducted among the overall sample and separately by male and female participants. Results showed patterns of significant associations between interpersonal violence victimisation and concussions among the overall sample and among male and female participants. Among the overall sample, any interpersonal violence victimisation (adjusted odds ratio [AOR] 1.45, 95% confidence interval [CI] 1.13–1.88), emotional abuse (AOR 1.36, 95% CI 1.06–1.76), physical abuse (AOR 1.61, 95% CI 1.07–2.44) and sexual assault (AOR 2.17, 95% CI 1.44–3.26) were associated with higher odds of any concussion history. Sexual assault victimisation had the strongest association with any concussion history among male (AOR 1.96, 95% CI 1.04–3.71) and female (AOR 2.96, 95% CI 1.62–5.43) participants. These results expand on prior interpersonal violence and concussion research by showing an association with multiple victimisation measures among a large and diverse sample of college students. Medical professionals should screen for concussions among college students who experience emotional abuse, physical abuse and sexual assault to provide appropriate guidance. Information on the symptoms of concussions should be incorporated into campus violence awareness and prevention efforts.     

Effects of a Rice Bran Dietary Intervention on the Composition of the Intestinal Microbiota of Adults with a High Risk of Colorectal Cancer: A Pilot Randomised-Controlled Trial

Rice bran exhibits chemopreventive properties that may help to prevent colorectal cancer (CRC), and a short-term rice bran dietary intervention may promote intestinal health via modification of the intestinal microbiota. We conducted a pilot, double-blind, randomised placebo-controlled trial to assess the feasibility of implementing a long-term (24-week) rice bran dietary intervention in Chinese subjects with a high risk of CRC, and to examine its effects on the composition of their intestinal microbiota. Forty subjects were randomised into the intervention group (n = 19) or the control group (n = 20). The intervention participants consumed 30 g of rice bran over 24-h intervals for 24 weeks, whilst the control participants consumed 30 g of rice powder on the same schedule. High rates of retention (97.5%) and compliance (≥91.3%) were observed. No adverse effects were reported. The intervention significantly enhanced the intestinal abundance of Firmicutes and Lactobacillus, and tended to increase the Firmicutes/Bacteroidetes ratio and the intestinal abundance of Prevotella_9 and the health-promoting Lactobacillales and Bifidobacteria, but had no effect on bacterial diversity. Overall, a 24-week rice bran dietary intervention was feasible, and may increase intestinal health by inducing health-promoting modification of the intestinal microbiota. Further larger-scale studies involving a longer intervention duration and multiple follow-up outcome assessments are recommended.     

Multi-Nutrient Fortified Dairy-Based Drink Reduces Anaemia without Observed Adverse Effects on Gut Microbiota in Anaemic Malnourished Nigerian Toddlers: A Randomised Dose–Response Study

Prevalence of anaemia among Nigerian toddlers is reported to be high, and may cause significant morbidity, affects brain development and function, and results in weakness and fatigue. Although, iron fortification can reduce anaemia, yet the effect on gut microbiota is unclear. This open-label randomised study in anaemic malnourished Nigerian toddlers aimed to decrease anaemia without affecting pathogenic gut bacteria using a multi-nutrient fortified dairy-based drink. The test product was provided daily in different amounts (200, 400 or 600 mL, supplying 2.24, 4.48 and 6.72 mg of elemental iron, respectively) for 6 months. Haemoglobin, ferritin, and C-reactive protein concentrations were measured to determine anaemia, iron deficiency (ID) and iron deficiency anaemia (IDA) prevalence. Faecal samples were collected to analyse gut microbiota composition. All three dosages reduced anaemia prevalence, to 47%, 27% and 18%, respectively. ID and IDA prevalence was low and did not significantly decrease over time. Regarding gut microbiota, Enterobacteriaceae decreased over time without differences between groups, whereas Bifidobacteriaceae and pathogenic E. coli were not affected. In conclusion, the multi-nutrient fortified dairy-based drink reduced anaemia in a dose-dependent way, without stimulating intestinal potential pathogenic bacteria, and thus appears to be safe and effective in treating anaemia in Nigerian toddlers.     

The Differential Effects of Social Media on Depressive Symptoms and Suicidal Ideation Among the Younger and Older Adult Population in Hong Kong During the COVID-19 Pandemic: Population-Based Cross-sectional Survey Study

BackgroundSocial media has become a ubiquitous part of daily life during the COVID-19 pandemic isolation. However, the role of social media use in depression and suicidal ideation of the general public remains unclear. Related empirical studies were limited and reported inconsistent findings. Little is known about the potential underlying mechanisms that may illustrate the relationship between social media use and depression and suicidal ideation during the COVID-19 pandemic.ObjectiveThis study tested the mediation effects of social loneliness and posttraumatic stress disorder (PTSD) symptoms on the relationship between social media use and depressive symptoms and suicidal ideation, as well as the moderation effect of age on the mediation models.MethodsWe administered a population-based random telephone survey in May and June 2020, when infection control measures were being vigorously implemented in Hong Kong. A total of 1070 adults (658 social media users and 412 nonusers) completed the survey. Structural equation modeling (SEM) and multigroup SEM were conducted to test the mediation and moderation effects.ResultsThe weighted prevalence of probable depression was 11.6%; 1.6% had suicidal ideation in the past 2 weeks. Both moderated mediation models of depressive symptoms (χ²₆₂=335.3; P<.05; comparative fit index [CFI]=0.94; nonnormed fit index [NNFI]=0.92; root mean square error of approximation [RMSEA]=0.06) and suicidal ideation (χ²₃₄=50.8; P<.05; CFI=0.99; NNFI=0.99; RMSEA=0.02) showed acceptable model fit. There was a significantly negative direct effect of social media use on depressive symptoms among older people (β=–.07; P=.04) but not among younger people (β=.04; P=.55). The indirect effect via PTSD symptoms was significantly positive among both younger people (β=.09; P=.02) and older people (β=.10; P=.01). The indirect effect via social loneliness was significant among older people (β=–.01; P=.04) but not among younger people (β=.01; P=.31). The direct effect of social media use on suicidal ideation was not statistically significant in either age group (P>.05). The indirect effects via PTSD symptoms were statistically significant among younger people (β=.02; P=.04) and older people (β=.03; P=.01). Social loneliness was not a significant mediator between social media use and suicidal ideation among either age group (P>.05).ConclusionsSocial media may be a “double-edged sword” for psychosocial well-being during the COVID-19 pandemic, and its roles vary across age groups. The mediators identified in this study can be addressed by psychological interventions to prevent severe mental health problems during and after the COVID-19 pandemic.     

Costs of Immunization Programs for 10 Vaccines in 94 Low- and Middle-Income Countries From 2011 to 2030

ObjectivesUnderstanding the level of investment needed for the 2021-2030 decade is important as the global community faces the next strategic period for vaccines and immunization programs. To assist with this goal, we estimated the aggregate costs of immunization programs for ten vaccines in 94 low- and middle-income countries from 2011 to 2030.MethodWe calculated vaccine, immunization delivery and stockpile costs for 94 low- and middle-income countries leveraging the latest available data sources. We conducted scenario analyses to vary assumptions about the relationship between delivery cost and coverage as well as vaccine prices for fully self-financing countries.ResultsThe total aggregate cost of immunization programs in 94 countries for 10 vaccines from 2011 to 2030 is $70.8 billion (confidence interval: $56.6-$93.3) under the base case scenario and $84.1 billion ($72.8-$102.7) under an incremental delivery cost scenario, with an increasing trend over two decades. The relative proportion of vaccine and delivery costs for pneumococcal conjugate, human papillomavirus, and rotavirus vaccines increase as more countries introduce these vaccines. Nine countries in accelerated transition phase bear the highest burden of the costs in the next decade, and uncertainty with vaccine prices for the 17 fully self-financing countries could lead to total costs that are 1.3-13.1 times higher than the base case scenario.ConclusionResource mobilization efforts at the global and country levels will be needed to reach the level of investment needed for the coming decade. Global-level initiatives and targeted strategies for transitioning countries will help ensure the sustainability of immunization programs.     

Loops and Building Blocks: a Knowledge co-Production Framework for Equitable Urban Health

This paper sets out a structured process for the co-production of knowledge between researchers and societal partners and illustrates its application in an urban health equity project in Accra, Ghana. The main insight of this approach is that research and knowledge co-production is always partial, both in the sense of being incomplete, as well as being circumscribed by the interests of participating researchers and societal partners. A second insight is that project-bound societal engagement takes place in a broader context of public and policy debate. The approach to co-production described here is formed of three recursive processes: co-designing, co-analysing, and co-creating knowledge. These ‘co-production loops’ are themselves iterative, each representing a stage of knowledge production. Each loop is operationalized through a series of research and engagement practices, which we call building blocks. Building blocks are activities and interaction-based methods aimed at bringing together a range of participants involved in joint knowledge production. In practice, recursive iterations within loops may be limited due of constraints on time, resources, or attention. We suggest that co-production loops and building blocks are deployed flexibly.     

Puumala Virus Infection in Family,Switzerland

We report 3 cases of Puumala virus infection in a family in Switzerland in January 2019. Clinical manifestations of the infection ranged from mild influenza-like illness to fatal disease. This cluster illustrates the wide range of clinical manifestations of Old World hantavirus infections and the challenge of diagnosing travel-related hemorrhagic fevers.