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General Information

A New World of Medicine: Monoclonal Antibodies.

I see monoclonal antibodies (mAbs) as the physicians’ everyday tools of the near future that will treat conditions as common as Osteoarthritis, Asthma, Diabetes mellitus and so on.  The earlier we start appreciating and getting comfortable with the increasing pharmaceutical repertoire of mAbs and their current indications, the easier our future as physicians.

One of the biggest and expanding benefits clinical medicine has derived from the explosion of Molecular Biology techniques is in the area of Biologics called Monoclonal Antibodies. A sizeable portion of ongoing biomedical research focus on the use of Monoclonal Antibodies to treat diseases with no or unimpressive treatments. As at 2013, about 338 Monoclonal Antibodies were said to be in human clinical trials or under the review of the U.S. Food and Drug Administration (FDA).1 These potential medications target a broad range of conditions cutting across Autoimmune diseases, Cancer, Respiratory disorders like Asthma, Diabetes, Digestive Disorders, Eye disorders, Infectious diseases, Musculoskeletal conditions and Neurologic disorders like Alzheimer’s disease  as well as Transplantation medicine.

Of interest is the increasing use of monoclonal antibodies in diagnostic medicine including immunohistochemistry and immunofluorescence. Equally fascinating is the use of mAbs in targeted delivery of therapies. A typical example is Ibritumomab (Zevalin), a combination of monoclonal antibodies with radioactive particles, delivers radioactive particles to cancer cells and it is currently used in the treatment of Non-Hodgkin’s lymphoma. Trastuzumab emtansine (Kadcyla) is a conjugate drug consisting of monoclonal antibody Trastuzumab (Herceptin) linked to the cytotoxic agents Emtansine. Trastuzumab exerts its action by binding to HER2/neu receptors on breast cancer cells expressing such receptors while the Emtansine component enters the cell and binds to tubulin and consequently destroy the cell. If you like you can call this the Double Approach Attack !

Amongst these immunotherapeutic agents, Nivolumab (Opdivo) is proving to be a wonder drug. Its indication has broadened from the initial approvals for squamous and non-squamous non-small cell lung cancer to include renal cell carcinoma with FDA approval of November 23, 2015.

Mechanisms of Action:

Monoclonal antibodies use one of the following mechanisms to exert their effects by binding to the target molecule thereby causing one of the following:

  • - blocking the function of the target molecules
  • - Inducing apoptosis in cells which express the target
  • - Modulating signaling pathways that involve the target molecule.
  • - It can also simply act as a delivery vehicle

 

Examples:

Some of the diseases benefiting from this exploding class of drug and the approved monoclonal antibodies are:

Autoimmune Diseases:

  • Rheumatoid Arthritis
  • Crohn’s Disease
  • Ulcerative Colitis
  • Ankylosing Spondylitis
  • Infliximab
  • Adalimumab (Humira)

Transplant Rejection

  • Basiliximab
  • Daclizumab

Asthma (Moderate to severe allergic Asthma)

  • Omalizumab (Xolair)

Systemic Lupus Erythematosus (SLE)

  • Belimumab

Psoriasis

  • Efalizumab (Raptiva)
  • Ustekinumab (Stelara)

Multiple Sclerosis

  • Natalizumab (Tysabri)

Postmenopausal Osteoporosis and Solid tumor’s bony metastases

  • Denosumab (Prolia, Xgeva)

Coronary angioplasty (Anticoagulation)

  • Abciximab

Macular Degeneration

  • Ranibizumab (Lucentis)

CANCER:

  •  

Colorectal carcinoma

  • Bevacizumab
  • Cetuximab
  • Ramucirumab

Neuroblastoma

  • Dinutuximab (Unituxin)

Melanoma

  • Ipilimumab
  • Nivolumab (Opdivo)
  • or combo of the two above

Non-Hodgkin’s lymphoma

  • Rituximab (Rituxan)

Breast Cancer positive for HER2/neu

  • Trastuzumab (Herceptin)

Lung cancer

  • Nivolumab
  • Pembrolizumab (Keytruda)

Multiple Myeloma

  • Daratumumab
  • Elotuzumab

Squamous cell carcinoma

  • Cetuximab
  • Nimotuzumab

B-Cell Leukemia

  • Alemtuzumab

Relapsed Acute Myeloid Leukemia

  • Gemtuzumab

Renal Cell Cancer

  • Nivolumab (Opdivo)

 

References:

  1. Medicines in Development 2013; Pharmaceutical Research and Manufacturers of America
  2. Immunotherapy Approvals in 2015; Cancer Research Institute; By Alexandra Mulvey.

 

Stay Current,

Dokun Dairo, MD


Recommended CPD Activity: H.pylori Infection in Clinical Practice

INTRODUCTION

Are you aware that the stomach is a no go area for most infectious agents? Yes, it is because of the over one billion parietal cells that produce hydrochloric acid at pH 1. However, when the pH is increased with acid suppressing drugs leading to low acidity, some infectious microbes could be found and in fact reside in the stomach. Similarly, some organisms have mechanical barriers around them, such as the encysted form of Entamoeba histolytica, and may escape the corrosive effect of gastric acid. Some organisms are also naturally endowed with the ability to produce an alkaline environment around themselves, thus neutralizing the acid environment and therefore able to survive in the stomach. One of such organisms is Helicobacter pylori!

ABSTRACT

Helicobacter pylori (H. pylori) infection has been strongly associated with gastroduodenal diseases that have high morbidities and mortalities. The infection is found worldwide, with a higher prevalence in developing countries and generally, areas of poor hygiene. Transmission is largely faeco-oral, but oro-oral transmission is also possible. By far the strongest association has...

    

   

Click Here to Read More And Earn MDCN Approved CPD Points

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Medenhanz Resources is an accredited ONLINE CPD provider by Medical and Dental Council of Nigeria (MDCN)

For inquiries, please call 08137740195 or send a mail to cpd@medenhanz.com
www.medenhanz.com


MedEnhanz CME Activity: Diabetic Ketoacidosis in Clinical practice

INTRODUCTION: In developing countries, mortality from DKA is about 20-50%, this is due to paucity of facilities for adequate care, shortage of insulin supplies and death of qualified caregivers. Thus the knowlege and understanding of DKA is essential to the 21st century practitioner. Prof. Kolawole a Fellow of the West African College of Physicians (FWACP), American College of Physicians (FACP) as well as a Fellow of the American College of Clinical Endocrinologists (FACE), has brilliantly in detail, provided a practical approach to the management of diabetic ketoacidosis, which is vital in daily medical practice.

ABSTRACT: Diabetes ketoacidosis (DKA) is a recognized consequence of the insulin deficient state that characterizes type 1 diabetes mellitus and less often type 2 diabetes. DKA is characterized by a high blood glucose level ≥ 14mmol/l, ketonaemia, ketonuria and metabolic acidosis (pH ≤ 7.3). Together with the Hyperosmolar Hyperglycaemic State (HHS), DKA constitutes two...

    

   

Click Here to Read More And Earn MDCN Approved CPD Points

http://www.medenhanz.com/cme-cpd.php

Medenhanz Resources is an accredited ONLINE CPD provider by Medical and Dental Council of Nigeria (MDCN)

For inquiries, please call 08137740195 or send a mail to cpd@medenhanz.com
www.medenhanz.com

 


Practice of Safe Blood Transfusion

INTRODUCTION: Dr. Benedict Nwogoh, a Consultant Hematologist has brilliantly distilled the essentials of safe transfusion of blood and its products, in a way that makes it easier for healthcare professionals to understand and apply in clinical practice. All stages of transfusion should be so handled to eliminate risk. Implementation of policies recommended by WHO requiring members to place safety at the heart of health priorities is of paramount importance in achieving safety in transfusion.

ABSTRACTIt is estimated that over 4.9million people require blood and blood products annually. Despite the challenges of getting adequate products, safety of blood and blood products is an important public health priority. Although enhancements in donor and blood screening have...

    

   

Click Here to Read More And Earn MDCN Approved CPD Points

http://www.medenhanz.com/cme-cpd.php

Medenhanz Resources is an accredited ONLINE CPD provider by Medical and Dental Council of Nigeria (MDCN)

For inquiries, please call 08137740195 or send a mail to cpd@medenhanz.com
www.medenhanz.com

 


Iron Deficiency Anaemia: Principles of Clinical Management

INTRODUCTION
Given the role of iron in oxygen transport and the low levels of available iron in the diets of a large proportion of the global population, it is assumed that iron deficiency is one of the biggest contributing factors to the global burden of anaemia. Consultant haematologist at Ahmadu Bello University, Dr. Aliyu A. Babadoko with his years of experience, has robustly presented the clinical approach to management of iron deficiency anaemia in the Sub-Sahara. 

ABSTRACT
More than 10 million lives are claimed every year by hunger and under-nutrition resulting in more than the deaths from AIDS, malaria and tuberculosis combined. Many of these people are affected by ...

    

   

Click Here to Read More And Earn MDCN Approved CPD Points

http://www.medenhanz.com/cme-cpd.php

Medenhanz Resources is an accredited ONLINE CPD provider by Medical and Dental Council of Nigeria (MDCN)

For inquiries, please call 08137740195 or send a mail to cpd@medenhanz.com
www.medenhanz.com

 


HYPOGLYCAEMIA IN CHILDREN: A PRACTICAL APPROACH TO MANAGEMENT


ABSTRACT
The term hypoglycaemia refers to blood glucose level below normal. Most of the time low blood glucose concentration is not associated with the development of the classic clinical manifestations of hypoglycaemia. The absence of clinical symptoms does not indicate that glucose concentration is normal or has not fallen below optimal level for maintaining brain metabolism.

Hypoglycaemia in the paediatric age group is a common clinical finding and is associated with a wide variety of disorders. Even in the Tropics, there is a growing awareness that hypoglycaemia can complicate many childhood illnesses. The condition often presents urgent diagnostic and therapeutic challenges. The major long-term sequelae of severe, prolonged hypoglycaemia are...

 

    

   

Click Here to Read More And Earn MDCN Approved CPD Points

http://www.medenhanz.com/cme-cpd.php

Medenhanz Resources is an accredited ONLINE CPD provider by Medical and Dental Council of Nigeria (MDCN)

For inquiries, please call 08137740195 or send a mail to cpd@medenhanz.com
www.medenhanz.com

 

 


SEPSIS: CLINICAL APPROACH TO DIAGNOSIS AND MANAGEMENT

INTRODUCTION
The knowledge of sepsis and its associated syndromes is vital in modern day medicine. An in-depth understanding of terms like sepsis, infection, septicemia, bacteremia; which have been used interchangeably by physicians for decades, is key to proper management and reduction in mortality globally in clinical practice.

Recent research in the developed world reveals that sepsis is dramatically increasing by an annual rate of between 8-13 % over the last decade, and now claims more lives than gastrointestinal and breast cancer combined.

ABSTRACT
Although the word sepsis is not new, our current definition of the Sepsis Syndromes started more than two decades ago with the publication of the consensus conference report. The origin of the word sepsis itself can be traced to a Greek word which refers to the the process by which flesh rots, swamps generate foul airs, and wounds fester due to the microbial mediated decomposition of organic matter. In 1992, the American College of chest physicians (ACCP) and the Society of Critical Care Medicine (SCCM) first published consensus conference definitions for sepsis syndromes. Sepsis was defined as a systemic inflammatory response to infection which is...

Click Here to Earn MDCN Approved CPD Points

http://www.medenhanz.com/cme-cpd.php

Medenhanz Resources is an accredited ONLINE CPD provider by Medical and Dental Council of Nigeria (MDCN)

For inquiries, please call 08137740195 or send a mail to cpd@medenhanz.com
www.medenhanz.com

 

 


Great Strides for Cystic Fibrosis

Cystic Fibrosis (CF) is an autosomal recessive inherited disease characterized by accumulation of mucus with markedly thick viscosity that causes damage to multiple organs in the body.

More than 20,000 people in the US have cystic fibrosis and it occurs when there is a mutation of thecystic fibrosis transmembrane conductance regulator (CFTR) gene. There are several mutations but the most common is the F508del mutation. This gene regulates sodium and chloride channels which helps control movement of water across tissues, this is necessary for the production of thin, freely flowing mucus.



Thus CTFR gene mutation thickens the viscosity of mucus across membranes forming occlusive clogs and scar tissue. This condition usually presents with symptoms that reflect damage mostly to the respiratory and gastro-intestinal systems. Other systems may be affected, however symptoms and their severity vary among individuals.

In the digestive system, CF may also cause meconium ileus which is as a result of occlusion of the intestinal tract in infancy. Mucus secretions in CF may also prevent vital secretions from the pancreas from being released and utilized by the body (e.g. Insulin), hence causing CF related Diabetes Mellitus in adolescence. This abnormally thick secretions can occlude the airways leading to severe respiratory problems including chest infections (staphylococcus aureus and pseudomonas aeruginosa). This may lead to permanent lung damage and formation of fibrotic scar tissue and deposition of cysts. Most men with CF develop congenital bilateral absence of the vas deferens, which may lead to male infertility. Other complications of cystic fibrosis include osteoporosis, cutaneous vasculitis, delayed puberty, psycho-social problems etc. In a meeting held in May 2015 which included a panel of 13 noted researchers and physicians.

The FDA approved the first drug for cystic fibrosis, a combo drug called ORKAMBI (Ivacaftor and Lumacaftor). The medication targets the F508del mutation; the root cause of CF rather than treating the severe symptoms. Orkambi is a product of Vertex Pharmaceuticals. It is indicated for patients with cystic fibrosis above the age of 11 years. Phase II clinical trials reveal a protective function of ORKAMBI in reducing pulmonary exacerbation rates, mean sweat chloride concentration and increasing forced expiratory volume.

The downside is that ORKAMBI is mutation-specific and does not target other variants of CF mutations. It also requires advice from the physician to educate the patient on possible side effects, haematological investigations, drug compliance and dietary changes. Currently research is on-going to produce a medication that treats all kinds of CF gene mutations. Early diagnosis and treatment still is the main-stay for survival.

Stay current,

Dr. Seun Odiase


References
1. The Lancet Journal (June 2014)
2. New England Journal of Medicine (NEMJ 2015)
3. Orkambi (FDA)
4. Genetics Home Reference
5. Cystic Fibrosis Australia


Modern Management of Pre-Eclampsia

Seasoned Obsterician/Gynecologist, Prof. Victor Oboro who is a professor of Obstetrics and Gynaecology at College of Health Sciences, Ladoke Akintola University highlights modern management of pre-eclampsia. Pre-Eclampsia and its complications are common presentations in primary, secondary and tertiary obstetric practice. This approved CPD material incorporates practice-changing nuances. Se abstract below and click the link to read full material to earn your CPD points and improve the care delivered to your patients.

ABSTRACT

Preeclampsia is defined as defined by the International Society for the Study of Hypertension in Pregnancy as gestational hypertension accompanied by at least one of the following: 1) significant proteinuria, 2) other maternal organ dysfunction or 3) uteroplacental dysfunction. Gestational hypertension is blood pressure of at least 140/90 mmHg on two separate occasions at least 4 hours apart occurring after 20 weeks of gestation. Significant proteinuria is any of 1) 2+ on urine dipstick; 2) at least 300mg in a 24 hour collection of urine or 3) protein/creatinine ratio of at least 30mg/mmol on spot urine or at least 1g/litres. Uteroplacental dysfunction is the presence of…….

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Doctors and Blindness from Diabetes

Aside from noncompliance on the part of patients and a system of health care in Nigeria plagued with poor regulatory and infrastructural problems, doctors could be amazed how we as care providers are contributing to the increasing prevalence of blindness and/or impaired vision from diabetic retinopathy (DR).

This write-up was inspired by the statement from one of the publications from Nigeria national blindness and visual impairment survey which says “As the epidemic of diabetes matures, visual loss from diabetic retinopathy (DR) will increase unless mechanisms for early detection and treatment improve, and health systems respond to the growing burden of non-communicable diseases”1. This large population-based study involving 13,591 participants aged ≥40 years put the prevalence of diabetes as 3.3%. About 48% of those diagnosed with diabetes in the study did not know they were diabetic while 20.5% of people with diabetes already developed diabetic retinopathy. That signals the magnitude of the threat of impaired vision and/or blindness from DR – a largely preventable and treatable condition.

The best way to determine our culpability in the huge gap in care of diabetic patients is to challenge ourselves individually by carrying out a performance improvement (PI) study in our clinical micro-practice with the aim to determine the percentage of patients with diabetes mellitus that we have personally referred or counselled on the need to see an ophthalmologist for routine eye screening for DR without the prompting of visual complaints from the patients. This PI exercise will not require too much of our time as the ancillary staff could be commissioned to collate raw data from the medical records while we take few hours to do the simple descriptive data analysis. I challenge any provider that feels too busy for this PI study to simply cast his/her mind back on the proportion of diabetic patients he/she has sent or counselled to see an ophthalmologist for routine eye examination in the last one or two years. This simple introspection could be equally revealing.

Rationale for Screening

Screening for diabetic retinopathy is important because the vast majority of patients who develop DR have no symptoms until the very late stages (by which time it may be too late for effective treatment). At that stage macular edema (ME) and/or proliferative diabetic retinopathy (PDR) are already present. The other reason cited is that the efficacy of laser photocoagulation in preventing visual loss from PDR and ME is well documented in randomized trials2.

American Diabetes Association Screening Recommendations3

  • Patients with type 2 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist shortly after the diagnosis of diabetes3.

  • Adults with type 1 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist within 5 years after the onset of diabetes3.

  • If there is no evidence of retinopathy for one or more eye exams, then exams every 2 years may be considered

  • If diabetic retinopathy is present, subsequent examinations for type 1 and type 2 diabetic patients should be repeated annually by an ophthalmologist

  • If retinopathy is progressing or sight threatening, then examinations will be required more frequently.

Role of Care-Givers

Health care providers can easily absolve themselves by doing those things that qualified them to be called care-givers. To our credit, we are reasonably good at those things – good glycaemic control, good blood pressure control and lowering lipid levels as appropriate. Beyond controlling blood sugar, it is the physician’s responsibility to counsel patients on need for routine eye screening and referral to an ophthalmologist.

Role of Health Care System

The system as a whole needs to be intentional in addressing vision impairments and/or blindness from DR. I suggest the following:

  • As our managed care system continues to evolve, there would be need for Health Maintenance Organizations (HMOs) to incentivize physicians on quality metrics that capture essential care for diabetic patients. Everyone responds to incentives!

  • Promotion and widespread procurement of digital retinal photographic equipment as a screening tool in areas where there is shortage of ophthalmologists. A trained ophthalmic technician is all that is required to do the screening and electronically send the photograph to an ophthalmologist for remote interpretation and reporting.

  • Schools of Health Technology should incorporate training in digital retinal imaging in their curriculum. This will help produce the critical mass of skilled ophthalmic technicians or ophthalmic nurses.

  • Of course, the overriding political will from governmental agencies like the Federal Ministry of Health cannot be downplayed.

Stay Current,

Dokun Dairo, MD

 

References:

  1. Fatima Kyari, Abubakar Tafida, Selvaraj Sivasubramaniam, et al. Prevalence and risk factors for diabetes and diabetic retinopathy: results from the Nigeria national blindness and visual impairment survey. BMC Public Health 2014, 14:1299

  2. Diabetic retinopathy: Screening. UpToDate

  3. Standards of Medical Care in Diabetes – 2014. Diabetes Care Volume 37, Supplement 1, January 2014

 


Approval of New Antibiotic

The cry of the world running out of efficacious antibiotics has been rising for the past 2 decades especially with increasing emergence of drug-resistant bacteria. Multi-drug resistant bacteria are well recognized as posing tremendous threat to global public health. When this is considered in the context of the dwindling interest in developing antibiotics, the situation can only be best described as a public health conundrum.

The new beta-lactamase inhibitor, Avibactam, gives a boost to the war against drug-resistant bacteria. The combination of this agent with the well-known cephalosporin, Ceftazidime, has been approved for marketing by the United States’ FDA. It is going to be marketed as Avycaz (ceftazidime-avibactam). It is indicated for treatment of complicated intra-abdominal infections (cIAI), in combination with metronidazole, and complicated urinary tract infections (cUTI), including kidney infections (pyelonephritis), who have limited or no alternative treatment options1

The other beta-lactamase inhibitors are clavulanic acid (used in combination with Amoxicillin as Augmentin or Ticarcillin as Timentin); sulbactam (used in combination with Ampicillin as Unasyn); and tazobactam (used in combination with piperacillin as Zosyn or Tazocin).

The armoury against beta-lactamse producing bacteria is again expanded by approval of ceftazidime-avibactam combination. Some of the common bacteria capable of producing beta-lactases include Staphlococcus, Klebsiella pneumoniae, Enterobacteriaceae, Morganella spp, Haemophilus influenza, and Neisseria gonorrhea amongst others. This is a strong signal to extended spectrum beta-lactamases (ESBL) producing bacteria to be on the run as drug manufacturers further fortify penicillins, cephalosporins and carbapenems. Kudos to the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act signed into law by President Barack Obama in July 2012 to incentivize pharmaceutical companies to develop antibacterial products to treat serious or life-threatening infections.

Hope the newer beta-lactamase inhibitor combinations find their way into National Agency for Food and Drug Administration and Control (NAFDAC) corridors for marketing approval soon.

References: 1. FDA Division of Drug Information.

Stay current,

Dokun Dairo, MD


MDCN Accepts Online CPD Transcripts from MedEnhanz

The Good news is MDCN now accepts online CPD transcripts from MedEnhanz Resources.

Following completion of the Medical and Dental Council of Nigeria’s mandated Pilot Study on delivery of online Continuing Professional Development (CPD) activity in Nigeria, MedEnhanz Resources has been accredited as a pioneer online CPD provider to Nigerian physicians and Dentists by the Council. This is a welcome development for Doctors and the MDCN’s CPD initiative. This is significant because the accreditation and regulatory framework for web-based CPD is different from traditional learning (in-person instruction) that existing providers of CPD are approved for.

Apart from fostering the mandate of MDCN on continuing professional development, MedEnhanz’s online CPD brings the following benefits to physicians:

  • Increase compliance with acquisition of 20 units of CPD for practicing license renewal

  • On demand access - anytime, anywhere – accessible to practitioners in rural areas on their tablet computer or smartphones

  • Flexible and self-paced study

  • Personalized CME from a variety of courses

  • No travel costs and no costs for closing clinic/hospital or finding coverage

  • Instant certification and opportunity to track CPD activities on archived transcripts

  • Access to diverse resource persons irrespective of experts’ location

MedEnhanz Resources is a company whose overriding philosophy is improving patient outcomes in Nigeria through its web-based point-of-care clinical reference tools and specialized educational activities tailored to the needs of Nigerian physicians.

The company promised to leverage its vast network of highly qualified network of authors and experts to provide up-to-date medical information based on current clinical guidelines and research. The educational materials are designed with a focus on practice improvement for physicians and better outcomes for patients. The team of Specialty Editors that comprise the editorial board not only ensure that educational contents are tropicalized but are based on Nigeria health infrastructure and environment.

Course formats and assessment are designed in tandem to programmes of international leaders in continuous medical education and will continue to evolve and positively impact the quality of care delivered at every level of Nigerian medical service system.


Ebola Response: Collaboration is Key

MedEnhanz joined other private sector leaders, United nations, government and civil society to highlight successful interventions by business in support of Ebola response, identify lessons learned, and explore longterm recovery strategies. Click link below for 5 takeaways from the conference.

http://unfoundationblog.org/5-key-takeaways-on-un-business-collaboration-for-the-ebola-response