Low radiation dose to treat pneumonia and other inflammations

Infection, the invasion of pathogenic microorganisms and viruses, causes reactive inflammation mediated by endogenous signals, with influx of leucocytes with distinct properties and capable of mounting a cellular or antibody response. Different forms of inflammation may also occur in response to tumours, in allergy and autoimmune disorders. Pneumonia, respiratory tract infection and septic shock for instance can arise as serious complications of the Covid-19 virus. While radiotherapy has been most widely used to control malignant tumours, it has also been used for treatment of non-malignant diseases, including acute and chronic inflammation in situations where anti-inflammatory drugs may be ineffective or contraindicated. The present review examines the history and prospects for low-dose anti-inflammatory radiation treatments, the present interest largely being motivated by the increased incidence of pulmonary disease associated Covid-19 infections. Evidence in support of the suggested efficacy are covered, together with an appraisal of one of the number of potential convenient sources that could complement external beam arrangements

Lessons on Ethical Decision Making from the Bioscience Industry

Mackie and colleagues performed over 100 interviews with managers and executives at 13 bioscience companies to learn about bioindustry ethics from their perspective

Primary HIV-1 Infection Among Infants in sub-Saharan Africa: HPTN 024.

Our objectives were to assess clinical signs and diagnoses associated with primary HIV-1 infection among infants. We analyzed data from a clinical trial (HIV Prevention Trials Network Protocol 024) in sub-Saharan Africa. Study visits were conducted at birth, at 4-6 weeks, and at 3, 6, 9, and 12 months. The study population comprised live born, singleton, first-born infants of HIV-1-infected women with negative HIV-1 RNA assays who were still breastfeeding at 4-6 weeks. Of 1317 HIV-1-exposed infants, 84 became HIV-1 infected after 4-6 weeks and 1233 remained uninfected. There were 102 primary and 5650 nonprimary infection visits. The most common signs were cough and diarrhea, and the most common diagnoses were malaria and pneumonia. Primary infection was associated with significantly increased odds of diarrhea [odds ratio (OR) = 2.4], pneumonia (OR = 3.5), otitis media (OR = 3.1), and oral thrush (OR = 2.9). For the clinical signs and diagnoses evaluated, sensitivity was low (1%-16.7%) and specificity was high (88.2%-99%). Positive predictive values ranged from 0.1%-1.4%. Negative predictive values ranged from 28.0%-51.1%. Certain clinical signs and diagnoses, although more common during primary HIV-1 infection, had low sensitivity and high specificity. Efforts to expand access to laboratory assays for the diagnosis of primary HIV-1 infection among infants of HIV-1-infected women should be emphasized

Deferasirox (Exjade®) significantly improves cardiac T2* in heavily iron-overloaded patients with β-thalassemia major

Noninvasive measurement of tissue iron levels can be assessed using T2* magnetic resonance imaging (MRI) to identify and monitor patients with iron overload. This study monitored cardiac siderosis using T2* MRI in a cohort of 19 heavily iron-overloaded patients with β-thalassemia major receiving iron chelation therapy with deferasirox over an 18-month period. Overall, deferasirox therapy significantly improved mean ± standard deviation cardiac T2* from a baseline of 17.2 ± 10.8 to 21.5 ± 12.8 ms (+25.0%; P = 0.02). A concomitant reduction in median serum ferritin from a baseline of 5,497 to 4,235 ng/mL (−23.0%; P = 0.001), and mean liver iron concentration from 24.2 ± 9.0 to 17.6 ± 12.9 mg Fe/g dry weight (−27.1%; P = 0.01) was also seen. Improvements were seen in patients with various degrees of cardiac siderosis, including those patients with a baseline cardiac T2* of <10 ms, indicative of high cardiac iron burden. These findings therefore support previous observations that deferasirox is effective in the removal of myocardial iron with concomitant reduction in total body iron

Grand Challenges in Global Health: The Ethical, Social and Cultural Program

The Grand Challenges initiative has 44 projects worldwide aimed at addressing diseases of the poor. What are the ethical, social, and cultural issues that the initiative faces

Generalizing Evidence from Randomized Trials using Inverse Probability of Sampling Weights

Results obtained in randomized trials may not easily generalize to target populations. Whereas in randomized trials the treatment assignment mechanism is known, the sampling mechanism by which individuals are selected to participate in the trial is typically not known and assuming random sampling from the target population is often dubious. We consider an inverse probability of sampling weighted (IPSW) estimator for generalizing trial results to a target population. The IPSW estimator is shown to be consistent and asymptotically normal. A consistent sandwich-type variance estimator is derived and simulation results are presented comparing the IPSW estimator to a previously proposed stratified estimator. The methods are then utilized to generalize results from two randomized trials of HIV treatment to all people living with HIV in the US

Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine

BACKGROUND: Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria. METHODS: We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz. RESULTS: At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥200 mg/g), and 11% had clinically significant albuminuria (UACR ≥30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR (P = 0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant interactions between NRTI and NNRTI/PI components. CONCLUSIONS: In this prespecified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings

Grand Challenges in Global Health: Ethical, Social, and Cultural Issues Based on Key Informant Perspectives

The authors interviewed key informants from the developing world and the Grand Challenges investigators to explore their ethical, social, and cultural concerns about the program

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio