Integrated analysis of different microarray studies to identify candidate genes in type 1 diabetes

Type 1 Diabetes is considered to be an autoimmune disorder that has been passed down through the genes. This research seeks the difference between the regular expression of gene versus the Type 1 Diabetes gene to understand the difference in expression at physiological levels. This was done in peripheral blood mononuclear cells for find new ways on improving beta cells. In this research, 199 samples of type 1 diabetes and 74 normal cells were taken from which 695 gene expressions were found. Out of 695 genes, 450 were up regulated and 245 down-regulated. More analyses was done on the cells to find specific cell targets for which the gene expressions were different. Signal transduction, molecular function, protein binding, arcahidonic acid metabolism were all part of this analysis.

From this research, an effort was made to understand the gene expression in different groups of people: one with type 1 and one without to understand if there can be any potential drug therapies that can be found. Using this genetic model, certain experimental drugs were found to be useful in blocking the specific target in the beta cells that could be further investigated on to better understand the efficacy of the drug on the specific site. As of now, type 1 diabetes has no cure except for maintaining the symptoms, but hopefully with research done on the gene expression and gaining a better understanding of the system, a drug can eventually be developed. In the future, how well do you think these genetic markers are going to play a role in exploring the potential drug for a treatment of a certain disease state?

 

Jia X, Yu H, Zhang H. (2016). Integrated analysis of different microarray studies to identify candidate genes in type 1 diabetes. 2016 Mar 1. doi: 10.1111/1753-0407. http://www-ncbi-nlm-nih-gov.pitt.idm.oclc.org/pubmed/26930153

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Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea

As Ebola virus disease (EVD) was at it’s peak, World Health organization brought up a list of drugs that could potentially be researched to treat Ebola. This research was originally set-up as a randomised trial, but due to high mortality rate, it was found to be unethical for many reasons. The main reason this research was made to be randomized was to avoid any implications that could arise from patients not recieveing treatment drug when they need to as it could lead to less people believing in the healthcare system. So, this research was randomized in which 99 patient’s data was represented in this study.

The study was done using Favipiravir, an antiviral that is used to treat severe influenza, to research it’s efficacy on patients with EVD. All of the patients were given either standard therapy treatment or treatment with experimental drug to see it’s efficacy. During this study of being non-randomized, it was seen that the patient’s with Ct count of less than 20 had high mortality rate than patients with Ct count of over 20. The data extracted from these patients was sufficient to consider whether this drug was efficacious for patients to use in the future, as this study was non-randomized and the the mortality of the patient was as predicted.

This study had no real results, but showed some potential of setting up a clinic for EVD patients. Knowing the ethical implications along with the clinical aspects of treating ebola is what this paper was implying. Although there was not any presentable data that could help with treatment of EVD, this paper helps understand some of the important aspects that a researcher will face if Ebola patients were used in a study. Would you use Ebola patients for your study? How can you justify if a person gets the treatment dose or not having randomized trial?

 

Sissoko D, Laouenan C, Folkesson E. (2016).Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea. 2016 Mar 1;13(3):e1001967.

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Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD

Anticholinergics are administered in two different dosing: one is used for 12 hours and second is used for 24 hours. These dosing where studied by Izquierdo and colleagues to find adherence in a large population of over sixteen thousand people. These people were not given anything different than their regular inhalers and were asked to keep their regimens similar to what they were on previously. This study monitored these people for a year and watched for adherence between people using 12 hours vs. 24 hours. Long-acting cholinergics (LAMA) were the main focus of the study, as the researchers believed that 24 hour dosing, which is one time dosing daily, will increase adherence in patients with COPD. As a result, adherence between both long-acting and regular were similar. LAMA was seen to have a very high adherence compared to twice daily dosing, but there was no evidence that showed that twice daily dose caused lower adherence.

This study was short but it’s an evidence towards something that pharmacists have been looking for in patients. Pharmacists role in the community is to help improve the adherence of patients medications with the right guidance and understand the community. This research studied proved that the difference between LAMA and twice daily dose was very similar, even though there was evidence that LAMA had higher adherence. This does not show particularly that patients should switch to one time dosing. Rather, this shows that the adherence comes from patients understanding as these patients in the research study were well explained about their use of anticholinergic for COPD. Would counseling every patient on how to use the medication and following up on the medication, help improve adherence for both LAMA and twice-daily dosing?

 

Izquierdo, J. L., Paredero, J. M., & Piedra, R. (2016). Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD. International Journal of Chronic Obstructive Pulmonary Disease, 11, 289–293. http://doi.org.pitt.idm.oclc.org/10.2147/COPD.S96948

The Antiviral Activity of Approved and Novel Drugs against HIV-1 MutationsEvaluated under the Consideration of Dose-Response Curve Slope.

This research article involved the production of several HIV-1 common mutation complexes via mutagenesis and the testing of various drugs (10 approved drugs and one novel drug) against these phenotypes to determine resistance. The IC50 (relative effectiveness) and slope of the inhibition curve were measured for each set of mutation-drug combinations. There was actually significant variation between the parameters measured for each resistance mutation based on the class of drug. For this reason, a new parameter called IIPatoxic was constructed by combining the parameters of IC50, slope, and the maximum limiting concentration of each drug. This study concluded that IC50 alone was not enough information to determine resistance mutations, and that new indices like IIPatoxic can better predict efficacies of drugs.

As we learn more about how drugs come to market and how they pass the clinical trials, this new study seems to be very important. As the pharmacist use drugs to treat HIV-1, new parameters are set in place to distinguish effective drugs from ineffective drugs. Something like IIPatoxic is a great way of differentiating drugs in the early stages because it blocks the ineffective drugs from hitting the market. This in turn reduces the chances of a patient diagnosed with HIV-1 from being on a treatment regimen that consists of a drug that is ineffective. Clinical researchers will need to find a new way of showing effectiveness of a drug excluding IC50. Are there any other tests that can be done currently that can show resistance mutation better than IC50?

Chang S., Zhuang D, Guo W. The antiviral activity of approved and novel drugs against HIV-1 mutations evaluated under the consideration of dose-response curve slope. 2016. http://www.ncbi.nlm.nih.gov/pubmed/?term=The+Antiviral+Activity+of+Approved+and+Novel+Drugs+against+HIV-1+Mutations+Evaluated+under+the+Consideration+of+Dose-Response+Curve+Slope.

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The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope

Global Hib vaccination: reasons to cheer and fear

Haemophilus influenza Type B (HiB) is one of the emerging vaccinations that has been discovered in the past several decades. This particular strain of influenza is known to affect children under the age of 5. The findings of this strain began in early 1930’s when research figured out that this was an secondary infection and the primary infection was the influenza virus itself. The secondary infection in children caused bacterial infections which caused severe fatalities. But developments and findings of different strains of Haemophilus influenza have shown that it can be contained as it affects different parts of the body. This particular type B influenza affects the CSF and blood in an infant’s body, and since then there has been research done to prevent this virus from having its effect on the body.

The vaccine for HiB was recently discovered in the last several decades and had a specific dosing regimen of 3 shots at an early age. Conjugated vaccines were made to help the low-income countries to eliminate the onset of this HiB in children. Since then, 90% of the countries have been using this conjugated vaccine in children. Globally, this vaccine is required to be taken 3 times at an early age, but due to resurgence in the disease in UK and Ireland, a booster shot was implemented in early 2000s. Since then the following question has arose: should a booster shot be required in the third-world countries that find it hard to pay for these vaccinations? Or should there be more research done on whether the resurgence of the disease occurs only in certain types of children, therefore not everyone will need the booster shot?

 

Howie, S. R. (2016). Global Hib vaccination: Reasons to cheer and fear. The Lancet Global Health, 4(3). Retrieved February 26, 2016. http://www.thelancet.com/journals/langlo/article/PIIS2214-109X(16)00006-1/fulltext

Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial

Tamoxifen is usually used for Ductal carcinoma other than the excising or doing a radiotherapy on it. Ductal carcinoma usually occurs in patients that have breast cancer and in this experiment, patients that were undergoing lumpectomy and radiotherapy were chosen. These post-menopausal women, were included in a study that compared tamoxifen and anastrozole to see the effects on the ductal carcinoma. This phase 3 trial design was set-up to be randomized, double-blinded study that occurred in 1552 participants in both treatment groups. The results at the end of the study, followed up by 9 years of monitoring, showed that 122 patients on tamoxifen and 90 patients in anastrozole were cancer-free. Between the two groups, the anastrozole was more gender and age related as it showed that women under age 60 had a better improvement than tamoxifen. This meant that women have more options to chose their treatment regimen from as both tamoxifen and anastrozole are potent drugs to treat ductal carcinoma.

I found this article very interesting as this trial showed that there are more potential drugs out there that can help eliminate ductal carcinoma. As an the study furthers, I believe this drug will show it’s true potential and since it’s more effective in women under 60, this will help the treatment regimen for those women. I think more aromatase inhibitors should be looked at in clinical trials to explore the potency of different drugs as it could be age specific for women above age 60 and can help treat ductal carcinoma in those women much faster.

 

Margolese, R. G., Cecchini, R. S., Julian, T. B. (2016). Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): A randomised, double-blind, phase 3 clinical trial. The Lancet, 387(10021), 849-856. Retrieved February 24, 2016. https://www-clinicalkey-com.pitt.idm.oclc.org/#!/content/journal/1-s2.0-S014067361501168X.

Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study

Ledipasvir-sofosbuvir is used for Hepatitis-C virus in treating genotype 5. This is a combination therapy in which Ledipasvir was an inhibitor for NS5A and Sofosbuvir was an inhibitor for NS5B. This research happened in France with 41 white ethnic origin in which 21 had previous exposure to the treatment and 20 were new to the drug. To understand the sequences of NS5B, BLAST analysis was used. A fixed dose of 90/400 mg Ledipasvir and Sofosbuvir was given to all patient and were monitored for 12 weeks for efficacy. In the study, 39/41 patients reached to end of the treatment and showed improvement and only two patients had a relapse after 4 weeks of treatment. This showed that the mixed treatment could be used for the treatment of HCV genotype 5.

I believe this research proved a great success and could be used in further treating more patients with HCV. But since this research is based on genomic sequence, and the target of the drug is to effect a specific sequence, then I don’t know how relevant this research would apply to a larger population. Since this research was focused on White ethnicity, it disregards any genetic change in other races, which can be a generalization that can be harmful to patients. The research should expand it’s inclusion criteria to patients from other ethnicities to understand the effects of the drug in a larger population.

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2815%2900529-0/fulltext

Abergel, A., Asselah, T., Metivier, S., et al. (2016). Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: An open-label, multicentre, single-arm, phase 2 study. The Lancet Infectious Diseases. Retrieved February 15, 2016.

Resistance to key HIV drug ‘concerningly common’

HIV has different phases through which the drug’s effectiveness decreases. As a first-line drug, Tenofovir, has been becoming less and less effective in population around the world. This raises concern, as first-line drug is needed to last a longer amount of time in  order to have it’s effectiveness in the treatment regimen. Patients in Africa are unable to afford second-line treatment medications even with the best treatment help from the doctors around with world. This causes patient adherence issues. HIV drugs need to be taken 85-90% of its treatment regimen, and if failed, it can cause drug resistance. Drug resistance in one patient can be a concern to other HIV patients as it is transmissible from one person to another. To avoid this, doctors are trying to reach out to patients and diagnose them at an earlier stage to reduce the cost in Africa and help them understand the importance of adherence.

I believe that this drug has a great ability to treat first phase of HIV in patients. But with drug resistance issues and financial needs in third world country, it makes it harder for this resistance to be constricted in one population. Resistance being able to spread from one person to another causes concerns in a population with less resources and becomes more important for the health care professionals in the that area to address that issue to the population. Physicians or pharmacist, the drug experts, are great resources that can help reduce the problem in this population as they can explain the potential side effects and treatment options to the population better than any other health professional.

Resistance to key HIV drug ‘concerningly common’ (2016, January 28). Retrieved February 11, 2016, from http://www.eurekalert.org/pub_releases/2016-01/ucl-rtk012516.php

http://www.eurekalert.org/pub_releases/2016-01/ucl-rtk012516.php