Monthly Archives: September 2019

Opioid Crisis: How big is the problem, and what are the solutions?

Drugs and Disease

What are opioids?

Opioids (Figure 1) are a class of drugs naturally found in the opium poppy plant that acts on the nervous system to produce a variety of effects, including the relief in pain or pleasure.

Opioid Use Disorder: How big is the problem?

Figure 1: Opioids [2]

 

The clinical term opioid use disorder, also known as opioid abuse, is a multidimensional health issue with complicated causes and no appropriate solution [3]. Therefore, the world is in the midst of an unparalleled, self-inflicted opioid epidemic [1]. In 2016, approximately 275 million people globally used drugs at least once and 27 million people were estimated to be suffering from opioid abuse. In 2015, around 4,50,000 people died as a result of drug use, of which 160,000 were directly related to drug use disorders and about 118,000 with opioid abuse. Approximately, a third and a half of all drug-related deaths are contributed by drug overdose [4].

 

Drug abuse: What are the contributing factors?

Over-prescription: It is one of the significant factors of drug abuse that not only affects adults but also youngsters and children. People who depend on opioids are most likely to get addicted and experience an adverse event [5]. Opioids are responsible for high proportion of fatal drug overdoses around the world because of their ability to cause respiratory depression and death, which can be identified by a triad of signs and symptoms as depicted in Figure 2.

Figure 2: Signs and symptoms of drug overdoses

 

Non- genetic factors: Some non-genetic factors also play a role in opioid addiction such as psychiatric disorder, substance abuse, depression, child abuse, or neglect. Certain personality traits such as impulsivity and sensation-seeking also increase the risk of opioid addiction.

Opioid as pain relievers: Easy or unrestricted availability of opioid pain relievers (medications used for pain relief that falls under the category of opioids) is another reason for high opioid abuse. A survey demonstrated that 22% of the respondents had opioids from an active prescription at home and 21% had medications leftover from the previous prescription of which 66% deliberately kept the medications at home in case there is a requirement in the future. Another survey by Thiels et al. found that more than 60% of pills prescribed by healthcare professionals went unused [6]. Few contributing factors that led to the presence of opioids at home were high family income and high caregiver educations. However, some critics say that the prevalence of opioids in home was not affected by one’s relationship with the youth, race, household type or Medicaid insurance [7]. It is essential that a combination of health, social, economic and lifestyle factors interact with genetic factors to determine an individual risk [3].

 

Opioid abuse: How to resolve the problem?

Basic life support and antagonistic drugs: Fortunately, overdose of opioid can be prevented if the basic life support and naloxone (opioid antagonist) are administered on time. This approach is adopted by many countries and jurisdictions to reduce deaths resulting from an opioid overdose [4].

Appropriate prescription procedures: Emphasis should be made on the proper prescription procedures and expectations of the patient regarding postoperative pain management to bridge the gap of unused opioids. Several approaches are needed to ameliorate the opioid overdose and other problems caused by the opioid abuse if administered measurably (Figure 3) [8]:

Figure 3: Steps to prevent opioid crisis

 

All these measures are a necessity to abate the opioid crisis. However, only half of the countries provide access to the effective treatment of opioid dependence, and less than 10% of the people who need the treatment are receiving it [8].

Drug abuse: What does WHO recommend?

WHO recommendations to prevent opioid crisis [3] are given below:

  1. WHO supports countries to administer the treatment where it doesn’t exist and also helps in monitoring trends in drug use and related harm to have a better understanding of opioid dependence and overdose
  2. WHO supports countries to use the medications rationally, to make the appropriate use of the drug and minimize the misuse/ overuse
  3. WHO recommends to take measures to alleviate the risk of misuse by a careful patient selection and supervising the doses whenever necessary
  4. WHO recommends that naloxone should be made available in the rehabilitation centers to manage opioid overdose and the people who are probably to witness an opioid overdose
  5. WHO provides psychosocial support, promotes detoxification and opioid maintenance treatment (which involves administration of drugs such as methadone and buprenorphine)
  6. A stepped approach was highlighted to manage the pain in cancer patients namely- the WHO cancer pain ladder that recommends initial use of non-opioids, followed by weak opioids and then strong opioids

Although the appropriate use of opioids is a fundamental part of modern analgesia, but the drug abuse has led the problem spin out of control. While there are people suffering from chronic and acute pain, opiates shall remain an essential class of medication in healthcare facilities. Proper emphasis should be given to understand the reasons why people are using these drugs and offer fewer stigmatizing strategies to assist people who use opioids. A three-point approach emphasizing on the prevention, treatment, and rehabilitation of those already affected and who might be at risk in the future may be the holistic solution. Further investigation and success with the prevention approaches and some new strategies devoted to managing the crisis are required in order to respond effectively to such conditions in the future.

 

Turacoz Healthcare Solutions aims to provide information on the latest trends, updates, and advances in the field of clinical research, trials and regulatory affairs. Turacoz Healthcare offers end-to-end support for scientific communications, clinical trial documents and disclosures, regulatory documents writing and submissions, and medico-marketing writing along with e-modules & e-books on healthcare and research.

 

References

  1. Health resources and service administration: [https://www.hrsa.gov/opioids, Accessed on 16th sep, 2019]
  2. John Hopkins Medicine Retrieved from: [https://www.hopkinsmedicine.org/opioids/what-are-opioids.html, Accessed on 16th sep, 2019]
  3. US National Library of Medicine: [https://ghr.nlm.nih.gov/condition/opioid-addiction#resources, Accessed on 16th sep, 2019]
  4. World Health Organisation Retrieved from: [https://www.who.int/substance_abuse/information-sheet/en/, Accessed on 16th sep, 2019]
  5. Stoicea, N., Costa, A., Periel, L., Uribe, A., Weaver, T., & Bergese, S. D. (2019). Current perspectives on the opioid crisis in the US healthcare system: A comprehensive literature review. Medicine, 98(20).
  6. Ziegelmann, M. J., Habermann, E. B., & Gettman, M. T. (2019, May). In Reply—The Importance of Educational Interventions and Regional Analgesia in Tackling the Opioid Crisis in the United States. In Mayo Clinic Proceedings(Vol. 94, No. 5, pp. 921-922). Elsevier.
  7. Garbutt, J. M., Kulka, K., Dodd, S., Sterkel, R., & Plax, K. (2019). Opioids in Adolescents’ Homes: Prevalence, Caregiver Attitudes, and Risk Reduction Opportunities. Academic pediatrics, 19(1), 103-108.
  8. Saloner, B., McGinty, E. E., Beletsky, L., Bluthenthal, R., Beyrer, C., Botticelli, M., & Sherman, S. G. (2018). A public health strategy for the opioid crisis. Public Health Reports, 133(1_suppl), 24S-34S.

 

Health Benefits of Nutraceuticals

Health & Fitness

Economic development of the people has improved their lifestyle. But the challenge that has arisen with this lifestyle change is increasing the prevalence of ‘lifestyle diseases.’ Lifestyle diseases refers to diseases associated with bad lifestyle choices including food habits. The increased trend of eating junk food is known to be the reason for several diseases (obesity, cardiovascular diseases) and nutritional deficiencies. Due to high cost of treatment of these diseases in the modern science, people have started looking for alternative or complementary treatment options. Thus, nutraceuticals came into focus and are being opted as they fulfill nutritional requirements and have therapeutic benefits.

The word “nutraceutical” was coined from “nutrition” and “pharmaceutical” by Stephen De Felice, founder and chairman of the Foundation for Innovation in Medicine in 1989. It is defined as “a food or parts of food that provide medical or health benefits, including the prevention and treatment of disease”.  Nutraceuticals are the pharmaceutically blended products that have both nutritional as well as the medicinal value. This type of product is designed to improve the physical health, and fight against day-to-day challenges such as stress, increase longevity, etc. It is a food supplement that plays a vital role in maintaining a healthy body and provides necessary supplements required for various metabolic processes to regulate body functions and thus protects the body from disease.

According to a Mordor Intelligence Report, the global nutraceuticals market is predicted to reach $671.30 billion by 2024.

Classification of nutraceuticals:

Nutraceuticals can be organized in several ways, depending upon its application and easier understanding. Some classifications can be based on academic instruction, clinical trial design, functional food development or dietary recommendations.

  • Based on food availability, they are divided into traditional nutraceuticals, obtained from nature directly, without any changes in the natural form and non-traditional nutraceuticals, foods enriched with supplements or biotechnologically designed crops to boost the nutrients
  • Based on mechanism of action, they are further classified with respect to specific therapeutic properties such as anti-microbial, anti-inflammatory, and antioxidants
  • Based on chemical nature, these are segmented depending upon their primary and secondary metabolite sources such as isoprenoid derivatives, phenolic substances, fatty acids, carbohydrates, and amino acid-based substances.

Nutraceuticals and their health benefits

Nutraceuticals are known to have therapeutics effects and physiological benefits. They are known to provide protection against various diseases including cardiovascular, obesity, diabetes, cancer, chronic inflammatory disorders, and degenerative diseases. Some of the food sources used as nutraceuticals and their therapeutic effects are discussed below:

  • Dietary Fibre– Dietary fibres are not hydrolysed by enzymes secreted by the digestive tract but by microflora in the gut. The benefits of consuming dietary fibres include the retardation of emptying of the gastric juices in the stomach thereby affecting the rate of digestion and the uptake of nutrients, and it improves glucose tolerance and lowers the risk of coronary heart disease, stroke, hypertension, diabetes, obesity and certain gastrointestinal (GI) disorders. Also, an increase in the intake of high fibre food improves serum lipoprotein values, lowers blood pressure level, improves blood glucose control for diabetes, and aids weight loss.
  • Probiotics– Probiotics are non-pathogenic, non-toxic anti-bacterial substances. These are resistant to gastric acid and adhere to gut epithelial tissues. Consumption of probiotics decreases the risk of systemic conditions like allergy, asthma, cancer, several infections of the ear and urinary tract. It is also used to treat GI conditions such as lactose intolerance, acute diarrhoea and antibiotic-associated GI side effects.
  • Prebiotics– It improves lactose tolerance, has anti-tumor properties, is capable of neutralizing toxins, stimulates the intestinal immune system, and helps reduce constipation, blood lipids and maintains safe blood cholesterol levels.
  • Polyunsaturated fatty acids (PUFAs) – These are very essential for all bodily functions and hence known as “essential fatty acids”. It can be only taken through diet. Omega-3-fatty acids are one on the best examples of PUFAs. The three major effects against cardiovascular diseases are anti-arrhythmic, hypolipidemic and antithrombotic. Its benefits are numerous, such as, it can help improve the health of pre-mature infants and patients suffering from asthma, bipolar and depressive disorders, dysmenorrhea and even diabetes. Infant formulas of omega-3-fatty acids nowadays contain docosahexaenoic acid (DHA) along with arachidonic acid, which closely mimic the breast milk. The FDA recommends a maximum of 3g/day intake of eicosapentaenoic acid (EPA) and DHA omega-3 fatty acids, with no more than 2g/day as a dietary supplement.
  • Antioxidant vitamins– Vitamins like vitamin C, vitamin E, and carotenoids are collectively known as antioxidant vitamins. These vitamins are self-sufficient and have synergistic effects. They prevent oxidative reactions leading to several degenerative diseases including cancer, cardiovascular diseases, cataracts etc.
  • Polyphenols– It has antioxidant, anti-inflammatory, anti-microbial, cardioprotective activities and plays a role in the prevention of neurodegenerative diseases and diabetes mellitus. Also, dietary polyphenols are believed (from in vitro studies) to affect numerous cellular processes like gene expression, apoptosis, platelet aggregation, intercellular signalling that can have anti-carcinogenic and anti-atherogenic implications.
  • Spices– These are responsible for lowering of blood cholesterol, prevention, and dissolution of cholesterol gallstones, protection of erythrocyte integrity in hypercholesterolemic condition, hypoglycaemic potential, amelioration of diabetic nephropathy. It also possesses antioxidant effect, anti-inflammatory and anti-arthritic effect, antimutagenic effect/cancer preventing, digestive stimulant action and antimicrobial activity.

People are trying to attain a healthier and a better quality of life by eating more vegetables, fruits, and other plant extracts, taking dietary supplements or nutraceuticals. The development of nutraceuticals and functional foods delivers unique products to the world at large and helps in enhancing consumer confidence. Nutraceuticals are substances that have physiological benefits or provide protection against chronic diseases. They are used to improve health, delay the aging process, prevent chronic diseases, increase life span, or support the structure or functions of the body.

Pharmacovigilance

Medical Writing

The term ‘pharmacovigilance’ was coined in the mid 70’s by a group of French pharmacologists and toxicologists to describe the operations encouraging evaluation of the risks and side effects potentially associated with drug treatment.(1, 2)The World Health Organization (WHO) defines pharmacovigilance as, ‘the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem’(3) It incorporates the processes involved in monitoring and evaluating adverse drug reactions viz., collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, biological products, blood products, herbals, vaccines, medical device, traditional and complementary medicines, with an aim to identifynew information about hazards and figuring out ways to safeguard patients from any potential harm.(2, 4)

Pharmacovigilance aims to:

    • Improve patient care and safety in relation to the use of medicines
    • Improve public health and safety in relation to the use of medicines;
    • Detect problems related to the use of medicines and communicate the findings in a timely manner.
    • Contribute to the assessment of benefit, harm, effectiveness and risk of medicines, leading to the prevention of harm and maximization of benefit.
    • Encourage the safe, rational and more effective use of medicines.
    • Promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public(5)

Pharmacovigilance Setup
A typical setup for pharmacovigilance studies includes people from various organizational units, people at various levels colluding to prevent drug related problems and thereby decreasing morbidity/ mortality rates. Figure 1 depicts the various functions of each party involved in a pharmacovigilance setup.(2)


Operational Overview
The process of pharmacovigilance begins with safety information coming in fromvarious sources, followed by processing and assessment of these reports to their relationship with the investigational product, and submission of the compiled report to the concerned regulatory authorities.Figure 2 summarizes the major activities associated with pharmacovigilance.(6)


Type of Data Collected
According to the, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline E2D, two types of safety reports are distinguished in the post-authorization phase, viz.,
a) Unsolicited Reports
b) Solicited Reports
Table 1 enlists the types of reports included in both the categories.(7)Table 1: Classification of Safety Reports [Adapted from: Good Pharmacovigilance Guideline Module VI (7)]

Data Collection Methods
The process of data collection in a pharmacovigilance setup is broadly of 3 types:
1.Passive data collection
2.Mandatory data collection
3.Active data collection

1.Passive Data Collection
Passive data collection also known as voluntary case reporting, involves active participation by health care providers in reporting adverse reactions and medication errors.

2. Mandatory data collection
Mandatory data collection is when manufacturers and pharmaceuticals must report information on adverse reactions gathered during post-marketing surveillance to the health authorities as per the country regulations.

3. Active data collection
Active data collection is a focused and structured data collection activity involving use of various tools such as trigger tools, patient chart audits, and direct observation methods.(8)

Data Collection Tools
Adverse drug reactions and medication errors are generally collected by filling a standardized form. For countries with a national pharmacovigilance program (e.g., India), the reporting forms are generalized throughout thecountry.(8) These are collected in different databases. For example, Adverse Event Reporting System (AERS), Eudravigilance, Vigiflow, etc.(9)
Figure 3 provides a country-wise list of database and adverse drug report forms.


Figure 3: Country-Wise Database and Adverse Drug Report Forms [Adapted from: Kumar A. et al.,(9)]
Data MiningData mining is the process of searching big data sets for interesting or useful information.(10) Data mining is used in the construction of literature-extracted knowledge databases as well as a method for detecting new potential drug interactions. Information retrieval and natural language processing (NLP) techniques are frequently used in data mining. (11)It also provides an “early warning system” to help identify drug safety issues. (12)
Many methods have been developed for data mining drug safety signals (early hints suggesting the possibility of adverse events) in pharmacovigilance, such as disproportionality analyses, text mining, natural language processing, change-point analysis, geographical information systems technology, visualization tools, etc.(13, 14)The most common of them are viz.,

a)Disproportionality Analyses
b)Text Mining(12)
a)Disproportionality Analyses

Disproportionality analyses is primarily used for data mining spontaneous reporting system (SRS) databases. It makes use of statistical methods such as, proportional reporting ratio (PRR) and multi-item gamma poisson shrinker (MGPS) to compare the observed count of a drug-adverse event combination with a background count for the adverse events for all other drugs or drug combinations in the database. (12, 14) Several software programs generate PRR and/or MGPS scores such as Empirica Signal™, PV-Analyser™, Molecular Analysis of Side Effects [MASE™], Empirica Study™, JReview™, and Statistical Analysis Systems (SAS™). (14)
b)Text Mining
The large volume of “unstructured” or “narrative” data submitted in the reports such as event descriptions or narratives in electronic health records, medical literature, social media, or the internet, require analysis with the help of ‘text mining’.(12)Vaccine Adverse Event Text Mining (VaeTM) system, search and retrieval framework (SARF), Linguamatics™ I2E, Georgetown Vaccine Information and Safety Resource (G-VISR) tool, MedWatcher Social, SAS Enterprise Miner™, etc., are the various tools used to perform text mining. (14)
Figure 4 describes the data mining methods used for different types of data.


Figure 4: Data Mining Tool for Different Types of Data[Adapted from: DuggiralaHJ. et al., (14)]New Trends in Pharmacovigilance
The current trends followed in the pharmacovigilance industry are elaborated below;

  • Contract outsourcing to increase operational efficiency
  • Use of secondary data sources that contribute to widespread adverse drug reaction reporting
  • Cloud-based reporting to bring a robust global database of adverse drug reactions accessible to all
  • Big data technologies to protect and assimilate huge amounts of information
  • Use of data analytics to improve data utilization
  • Automation in the pharmacovigilance process to increaselabor efficiency
  • Artificial intelligence to overcome the drawbacks with traditionalpharmacovigilance services

Social Media and Pharmacovigilance
The Internet and social media has changed people’s mindset in relation to health care. According to the Pew Research Center’s Internet & American Life Project 2013, 72% of internet users admitted looking online for health information of some kind. (15) Social networks, forums and blogs have become a major platform for patients to share their therapy experiences, including adverse drug reactions. (16) Reports from social media sources are much rapid, occurring in close proximity to the event and are potentially richer sources than those reported through healthcare professionals. (17)
Figure 5 describes the ways in which pharmacovigilance teams can use social media to participate and enhance product safetyawareness.


HCP, Health Care Professional; PV, Pharmacovigilance.
Figure 5: Use of Social Media to Engage and Improve Awareness About Product Safety[Adapted from: The Impact and Use of Social Media in Pharmacovigilance (17)]The ICH-GVP, Council for International Organizations of Medical Sciences (CIOMS) Guidelines and the US FDA Guidelines provide guidance to the pharmaceutical industry for development and implementation of their social media strategies for pharmacovigilance. (7, 18, 19).Benefits of social media in pharmacovigilance are listed below (Figure 6).

HCP, Health Care Professional.
Figure 6: Benefits of Social Media on Pharmacovigilance[Adapted from: The Impact and Use of Social Media in Pharmacovigilance (17)]

Conclusion
Pharmacovigilance is an important discipline in managing adverse reactions of healthcare products.(20) It is based on the qualitative and quantitative research of reports of spontaneous adverse drug reactions, followed by a clinical evaluation of its effect on the drug’s general safety profile. Pharmacovigilance can promote public health programs by offering continuing information throughout the life cycle of a product, enabling a precise, reliable and balanced evaluation of the product’s risk-benefit ratio as more and more information becomes accessible with its use. (21) Pharmacovigilance’s fundamental goal is the secure use of drugs, safety of patients, and the protection of public health. To achieve this goal, national regulators and international organizations should be empowered to report more adverse reactions to health care professionals and the public.

References
1.McBride WG. Thalidomide and congenital abnormalities. Lancet. 1961;2(1358):90927-8.
2.Suke SG, Kosta P, Negi H. Role of pharmacovigilance in India: An overview. Online journal of public health informatics. 2015;7(2).
3.Pharmacovigilance 2019 Available from: https://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/.
4.Pharmacovigilance: Ensuring the Safe Use of Medicines – WHO Policy Perspectives on Medicines2004 19 July 2019. Available from: http://apps.who.int/medicinedocs/en/d/Js6164e/.
5.The safety of medicines in public health programmes: Pharmacovigilance an essential tool. 2006. Available from: https://apps.who.int/iris/bitstream/handle/10665/43384/9241593911_eng.pdf.
6.Gagnon S, Schueler P, Fan JD. Pharmacovigilance and risk management. Elsevier; 2012. p. 141-59.
7.EMA. Guideline on good pharmacovigilance practices (GVP) Module VI2017 22 July 2019. Available from: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-good-pharmacovigilance-practices-gvp-module-vi-collection-management-submission-reports_en.pdf.
8.Pharmacovigilance. 2012 [cited 22 July 2019]. In: Management Sciences for Health [Internet]. [cited 22 July 2019]; [35.1-.19].
9.Kumar A, Khan H. Signal Detection and their Assessment in Pharmacovigilance. Open Pharmaceutical Sciences Journal. 2015;2(1).
10.Hand DJ, Blunt G, Kelly MG, Adams NM. Data Mining for Fun and Profit. Statistical Science. 2000;15(2):111-26.
11.Vilar S, Friedman C, Hripcsak G. Detection of drug–drug interactions through data mining studies using clinical sources, scientific literature and social media. Briefings in bioinformatics. 2017;19(5):863-77.
12.Ventola CL. Big Data and pharmacovigilance: data mining for adverse drug events and interactions. Pharmacy Therapeutics. 2018;43(6):340.
13.Hauben M, Madigan D, Gerrits CM, Walsh L, Van Puijenbroek EP. The role of data mining in pharmacovigilance. Expert opinion on drug safety. 2005;4(5):929-48.
14.Duggirala HJ, Tonning JM, Smith E, Bright RA, Baker JD, Ball R, et al. Use of data mining at the Food and Drug Administration. Journal of the American Medical Informatics Association. 2015;23(2):428-34.
15.Fox S, Duggan M. Health online 2013. Health. 2013;2013:1-55.
16.Lengsavath M, Dal Pra A, de Ferran A-M, Brosch S, Härmark L, Newbould V, et al. Social media monitoring and adverse drug reaction reporting in pharmacovigilance: an overview of the regulatory landscape. Therapeutic innovation regulatory science. 2017;51(1):125-31.
17.The Impact and Use of Social Media in Pharmacovigilance2018. Available from: https://www.sciformix.com/wp-content/uploads/Social_Media_in_PV_Whitepaper.pdf.
18.Administration; FD. Good pharmacovigilance practices and pharmacoepidemiologic assessment. Center for Drug Evaluation Research. 2005.
19.V. CWG. Current Challenges in Pharmacovigilance: Pragmatic Approaches: Report: CIOMS; 2001.
20.Nour S, Plourde, G. Pharmacovigilance. 2019. In: Pharmacoepidemiology and Pharmacovigilance: Synergistic Tools to Better Investigate Drug Safety [Internet]. [7-23].
21.Nour S, Plourde, G. Conclusion. 2019. In: Pharmacoepidemiology and Pharmacovigilance: Synergistic Tools to Better Investigate Drug Safety [Internet]. [137-8].