Monthly Archives: May 2019

Osteoporosis: Overview and Recent Advances in its Management

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Osteoporosis is a silent age-related skeletal disease characterized by loss of bone mineral density and microarchitectural deterioration leading to increased fragility and susceptibility to fractures. The most common sites of fracture are femoral neck, lumbar spine and distal forearm which more than often are debilitating and disabling if not intervened. Osteoporosis has affected more than 200 million people worldwide, with almost 8.9 million fractures reported annually across the globe. Close to 30% of postmenopausal women in America and Europe suffer from osteoporosis while India estimates not less than 50 million of its people in the plexus of this debilitating bone disease. The overall impact of osteoporosis is presented in Table 1.

Impact of osteoporosis
Table 1: Impact of osteoporosis

Assessed by a T score of less than -2.5 (World Health Organization definition in Figure 1) and a Z score significantly higher or lower than the average, osteoporosis may operationally be classified as the following 2 types:

Postmenopausal (type I): Linked to the fall in oestrogen levels, this type affects women between 50 and 70 years of age.

Senile (type II): Affects both men and women over the age of 70, but predominantly women.

Figure 1: Understanding the T-Score

Risk Factors for Osteoporosis

Using Fracture Risk Assessment Tool Model (FRAX) algorithms, several risk factors have been recognized that predispose men and women to osteoporosis. Smoking, alcohol consumption, high salt intake, immobilization, sedentary life, excessive weight loss reducing the BMI below 18.5 kg/m2, inadequate exposure to sun and socioeconomic factors have been shown to be significantly associated with its risk and incidence. The most common risk factors are shown in Figure 2, of which, modifiable factors like declining levels of sex hormones, anorexia nervosa, low calcium and vitamin D intake are attributed to faulty lifestyle. Public awareness campaigns have been spreading their annex to educate and motivate necessary changes towards preventing osteoporosis.

Figure 2: Common osteoporotic risk factors

RECENT ADVANCES IN OSTEOPOROSIS

Diagnosis

With one in three women and one in every five men over the age of 50 years worldwide are being estimated to face the risk of osteoporotic fractures in their lifetime [1], inclusion of diagnostic tests for bone health in their health check-up plans to help them get therapeutic or preventive measures in time becomes imperative.

  • Dual energy X-ray absorptiometry (DXA): Stands as the gold-standard for diagnosis of osteoporosis by determination of bone mineral density (BMD). However, the high capital cost of DXA created a need for alternative diagnostic tools.
  • Bindex®: Recently approved by United States Food and Drug Administration (USFDA) for osteoporosis diagnosis, it is a portable hand-held instrument that measures with 90% sensitivity and specificity, cortical bone thickness of the tibia. The algorithm calculates the density index, a parameter which estimates BMD at the hip as measured with DXA.
  • OsCare Sono: This is another inexpensive and small portable ultrasound-based instrument that measures bone strength from the forearm radial bone. It provided measurement results in a few minutes and they correlate well with bone cortical thickness, bone elasticity and BMD, including BMD of the deeper cortical layers. These attributes suggest a promising device that offers enhanced sensitivity to early osteoporotic changes.

Treatment

Currently, to accost the imbalance between bone resorption and build-up in osteoporosis, anti-resorptive and osteoanabolic agents crown the list and fall under the first and second line of therapy [9].

  • Bisphosphonates which bind to bone mineral and also inhibit bone osteoclast activity (resorption), are anti-resorptive agents which mainly increase the trabecular BMD and are one of the reliable and cost-effective first-line therapy options for both primary and secondary osteoporosis.  
  • Denosumab, a human monoclonal antibody, inhibits RANKL-induced bone resorption and increased cortical BMD.
  • Teriparatide is an N-terminal 34-amin acid long peptide of the parathyroid hormone which again acts on increasing lumbar BMD and contributes to prevention of vertebral and non-vertebral fractures.
  • Abaloparatide is again a peptide 34-amino acid long and belonging to the N terminal region of PTH-related protein. It has shown to be effective in increasing the lumbar spine- and proximal femoral BMD.
  • Romosozumab, an anti-sclerostin humanized monoclonal antibody, is shown to increase the lumbar spine- and proximal femoral BMD.

Table 2 gives a brief glance over the current mediation used to treat osteoporosis with their trade names.

Medications for osteoporosis
Table 2: Medications for osteoporosis

Apart from these current ones, there have been a surge in development of more efficacious drugs for osteoporosis management (Table 3).

Recent therapeutic agents for osteoporosis
Table 3: Recent therapeutic agents for osteoporosis

A minimally invasive targeted treatment in which local bone loss due to osteoporosis is restored by implanting a unique material that is resorbed and replaced by bone, is being offered as Ossure LOEP (local osteo-enhancement procedure) kit by AgNovos, USA. Also, during the last decade, vertebroplasty and kyphoplasty has also evolved as an effective surgical procedure in certain cases with subacute pain, oedema and focal joint tenderness.

THE KNOWLEDGE-PRACTICE GAP

Despite path-breaking diagnostic and therapeutic advances, there exists a lacuna in their application and compliance. Osteoporosis stays unfortunately and vastly, underdiagnosed and undertreated, and identifying these gaps in patient care becomes indispensable. A few of them are listed below:

  • Failure to follow screening guidelines for osteoporosis by physicians leading to erroneous assumptions and subsequent lack of appropriate treatment plan.
  • Inefficacy to treat patients sustaining fragility fracture with a timely intervention reducing the likelihood of preventing future fractures. One of the commonly observed reason is concerns around side effects of drugs like bisphosphonates, etc. which lead to reluctance from physicians in prescribing medicines and challenges in compliance by patients.
  • Underestimating the menace of osteoporosis especially by women who are more at risk but are unfortunately lesser concerned about its consequences; poor communication with physicians and non-compliance of screening and diagnostic recommendations puts patients at irreversibly damaging risks.
  • Inadequate follow-up and non-adherence by patients during the treatment regimen.
  • Insufficient funding and reimbursement of exorbitant diagnostic and therapy costs also remaining one of the main reasons why osteoporosis lies low on the priority list of patients.

PREVENTION

Rebuild. Refuel. Renew.

Although lifestyle choices, genetics and systemic diseases, and even certain medications pose as substantial risk factors, the good news is that osteoporosis is preventable.

  • Weight bearing and cardiovascular exercises: These not only work towards building muscles, but also strengthen bones, ligaments and tendons. In turn they improve agility, strength, balance and posture, considerably reducing the risks of fractures.
  • Dietary calcium and vitamin D3 intake: Falling on the fundamentals of skeletal science, calcium and vitamin D stay incontestable for bone health. A good balanced diet and adequate exposure to sun are always the safest choices to regulate calcium and vitamin D3 levels,
  • Supplements: calcium and vitamin D3 supplements are also often opted in times of nutritional inadequacy. Yet, concerns over prolonged supplementation causing serious adverse effects like hypercalcemia and hypercalciuria, have been cropping up lately. The U.S. Preventive Services Task Force (USPSTF) recently recommended “against daily supplementation with 400 IU or less of vitamin D3 and 1,000 mg or less of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women”.

“A thousand tiny steps can conquer the tallest tower”

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 provides an 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.

Here is Everything You Should Know About Cystic Fibrosis

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The month of May is commemorated as Cystic Fibrosis Awareness Month. It aims at raising awareness about cystic fibrosis (CF). Cystic fibrosis foundation (CFF) sponsors this month.

According to estimates, more than 70,000 people globally are affected by cystic fibrosis, but the prevalence of the condition varies globally. The US alone accounts for around 30,000 people living with cystic fibrosis. Around 1000 new cases of cystic fibrosis are diagnosed every year in the US. More than 75% of these cases are of children of age 2 or below. Asia and Africa are thought to be under-diagnosed for CF. Many nations don’t screen for CF in new-borns unlike the US, and the nation registries suffer from lack of data.

What is Cystic Fibrosis (CF)?

CF is a genetic disease that has an impact on lungs and digestive system of human body. Under the influence of this condition, the body produces thick and sticky mucus that can lead to blockage of lungs and obscure pancreas.

In individuals with CF, metamorphosis in the cystic fibrosis transmembrane conductance regulator (CFTR) gene makes the CFTR protein debilitated. When this protein doesn’t function properly, it is incapable of moving chloride- a salt component- to the surface of cell. Without the chloride to bring water to the surface of cell, the mucus in different organs turns thick and sticky.

The mucus blocks the airways and entrap germs such as bacteria, in the lungs, which lead to infections, soreness, respiratory issues and other complications. The people with CF need to be extra cautious and avoid contact with germs.

The thickening of mucus can also lead to infertility in males by clogging the vas deferens or the tube responsible for carrying sperms from testes to urethra.

Symptoms of CF:

Mentioned below are some prominent symptoms of cystic fibrosis:

  • Skin tasting very salty
  • Continual coughing
  • Running out of breath
  • Breathing roughly/heavily
  • Persistent lung infections inclusive of pneumonia or bronchitis
  • Problem with gaining weight despite of heavy diet
  • Infertility in males
  • Greasy and heavy stools
  • Troubles with bowel movements
  • Nasal polyps or slight fleshy growth in the nose

Due to the obstruction in lungs, infections like bronchitis and pneumonia can occur in the patient, leading to growth of pathogens. Blockage in pancreas contribute to malnutrition and poor growth. The risk of developing osteoporosis and diabetes is also associated with it.

Causes of Cystic Fibrosis:

Since CF is a genetic disease, to be affected by it one is required to inherit the mutated gene from both of their parents. The mutated genes are the carriers of codes that produce protein controlling the flow of salt and water on the surface of organs, inclusive of pancreas and lungs.

People suffering from CF struggle with the balance of salt and this leads to more salt and water on the surface of cells and formation of very thick mucus.

Individuals with a single copy of the mutated gene are known as carriers. They do not fall prey to the condition or symptoms of CF. For someone to be affected by CF, both their parents must be the carriers.

If two people are carriers and have a child together, there are:

  • 25% chances that the kid will have CF
  • 50% chances that the kid will be a carrier, but won’t suffer from CF
  • 25% chances that the kid will neither be the carrier and nor suffer from CF

Treatment for CF:

At present, CF is not curable. Certain treatments work on controlling the symptoms and improving quality of life for CF patients. Depending on the kind and intensity of symptoms, the treatments are personalized.

Clearing airway

It is very important for CF patients to reduce the level of mucus in their lungs in order to breathe easily and avoid any lung infections.

Airway Clearance Techniques (ACT) helps individuals with CF to soften their mucus and get rid of it from their lungs. Inhalable medications are effective in reaching the airways and are usually used. The medication can be given through aerosol or through inhalers. These medications help in thinning mucus, killing bacteria and setting off mucus to enhance airway clearance.

Antibiotics act as an essential part of routine care. These can be consumed orally, through injecting and inhalation. Some other medications like azithromycin and ibuprofen are said to protect and enhance lung function and now made a part of standard therapy for CF patients.

CF patients can lower the risk of developing lung infections by taking the below mentioned steps:

  • Washing hands often
  • Avoid smoking
  • Avoid futile contact with people suffering from cold or other contagious diseases
  • Getting a flu injection every year

Other styles of treatment:

Other than the airway clearance technique, there are other types of treatment too.

Implanted devices:

These allow long-term contact with the bloodstream for constant supervision of drugs. These are capable of making the management of CF more powerful and less invasive.

CFTR Modulators:

CFTR (CF Transmembrane Conductance Regulator) modulators are the recent medications developed to focus on the defective CF-causing gene. They help in easing the flow of salt and fluids on the expanse of lungs and weed out the heavy mucus that CF patients generally form in their lungs.

At present, two CFTR modulator brands are certified by FDA (Food and Drug Administration), namely Orkambi and Kalydeco. They’re recommended for children suffering from 10 distinct mutations of the CF-causing gene. Kalydeco might be recommended for kids of age 2 years or more, whereas Orkambi is for kids aged 6.

Remedial measures based on Nutrition:

CF affects the digestive system adversely and the patient suffers from poor nutrient absorption. It is recommended that CF patients should consult their doctor regarding their diet. A nutritionist would assist them in having a control of digestive symptoms.

To balance the digestion of nutrients, a variety of additional supplements like pancreatic enzyme supplements, vitamins or salt might be required along with a specific kind of diet.

CF is responsible flawed growth. To ensure proper development and growth in affected children, a diet rich in calorie and fat, is very essential. It also helps adults in maintaining optimum health. Good nutrition is very crucial for CF patients so that they can be safeguarded against high risk of lung infection.

Cystic fibrosis cannot be cured as of now but with proper care, treatment and diet, the symptoms of it can be controlled. The average life expectancy of CF patients is early 40s. The life expectancy may vary based on the intensity of the symptoms, age of diagnosis and the kind of mutation in gene.

The life expectancy of CF patients has increased significantly in last few years, being around 47 years. There are many patients living well in their 50s or 60s.

Turacoz healthcare solutions, a medical communications firm, believes that appropriate treatment and caution is the key to control currently incurable diseases like cystic fibrosis. Turacoz provides cost-effective medical writing services like regulatory writing, publication writing, advisory board meetings, etc. To know more about Turacoz and to avail the services, drop a mail at [email protected]

Talc, a cosmetic ingredient: Safety issues

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Most of us have possibly used it or sprinkled on our skin at some point in our life, ‘Talc’ which is a processed from of soft mineral compound of magnesium silicate and is called talcum powder or just talc in general terms. The natural smoothness and adsorbency of talc have been utilized since millennia and its use dates back to the Egyptian time. Some of the major brands utilizing talc’s adsorbent properties are Nivea, Pond’s, Cinthol and Johnson & Johnson. Ideally, cosmetic grade talc should not contain asbestos but recent lawsuits against Johnson & Johnson have claimed its presence in the marketed cosmetic products.

Non-clinical Findings

In 1993, the National Toxicology Program (NTP) in their report stated that there were some evidence of carcinogenic activity in male F344/rats, clear evidence of carcinogenic activity in female F344/N rats, and no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to aerosols of 6 or 18 mg/m3 non-asbestiform cosmetic grade talc in a lifetime study. In 2010, the International Agency for Research on Cancer (IARC) Working Group reported that there is a limited carcinogenicity evidence for talc (not containing asbestos/asbestiform fibres) in experimental animals.

Clinical Safety Alerts

Talc has been safely used and is well tolerated since many years and recent scientific reviews on available data have supported this position lately. However, the first alert associated with genital was reported by identification of talc particles in ovarian cancers which came in 1971.

This finding was strongly contested by Dr G.Y. Hildick-Smith, Johnson & Johnson’s medical director. A subsequent publication in the Lancet warned that “The potentially harmful effects of talc in the ovary should not be ignored”. This warning was confirmed in a 1992 Obstetrics & Gynaecology publication, reporting that a woman’s frequent talc uses on her genitals increased her risk of ovarian cancer by threefold. The talc in question was simple brand or generic ‘baby powder’.

Unexpectedly, the mortality of ovarian cancer in women over 65 years of age has escalated sharply, especially in black women who have a higher rate of talc use as compared to other races. Almost 16,000 women in the United States die from ovarian cancer yearly, by some estimates, one out of five women regularly applies talc to her genitals either via direct application, or from tampons, sanitary pads and diaphragms that have been dusted with talc.

Conclusion

IARC reports perineal use of talc-based body powder to be possibly carcinogenic (Group 2B) in humans, and that inhaled talc (without asbestos or asbestiform fibres) is not classifiable as to its carcinogenicity (Group 3). Additionally, the US Cosmetic Ingredient Review Expert Panel published a safety assessment of talc as used in cosmetics. It concluded that talc is safe for use in cosmetics in the present practices of use. Johnson & Johnson faced continued concerns on about the threat posed by lawsuits over the safety of the company’s signature baby powder. The company has always denied the allegations and maintained a swift stance on the safety of talc.

At Turacoz Healthcare services, we provide end to end toxicology and regulatory assistance to meet the high standards set by the regulators worldwide. We provide exhaustive toxicology/safety literature search from pre-clinical to post-marketing stage. We provide consultation at various stages of product lifecycle in order support the ingredient compliance with the guidelines of respective regulatory bodies.

Medical Diagnostics: An Update

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Diagnostics play a very important role in our everyday life, be it for a disease, condition or identification of a risk factor. Various diagnostic advancements viz. novel techniques, devices, pathology and laboratory services, etc. are introduced regularly in the market by companies across the globe to help improve the lives of people and ensure quality‑care for patients.

The first quarter of 2019 featured some important updates on medical diagnostic and innovations and some are shared below:

  • Paper-based LAMP Diagnostics for Detecting Malaria

According to the World Malaria Report 2018, 219 million people were affected by malaria in 2017. Diagnosing the same is difficult in rural areas and in developing countries. Keeping the disease burden and non-accessibility in mind, scientists have developed a low-cost portable device which accurately and efficiently detects malaria. The technique uses a paper infused with loop-mediated isothermal amplification, LAMP, which involves printing with hydrophobic wax using a commercial printer and then heating the paper on a hot plate to bind the wax with the paper [2]. The paper attached to a lateral flow device helps in containing the blood sample (DNA) for the detection of malaria. This device uses amplification and detection techniques which help in identifying Plasmodium falciparum, the malarial parasite. This device was used to detect malaria in 67 school children from 2 different schools in Uganda. The results were also compared to the gold standard test in malaria, PCR. The new device showed promising results by identifying 98% of the malaria cases and is now undergoing further research for proper implementation.

  • Objective Diagnosis for PTSD

Posttraumatic stress disorder is associated with functional impairment involving delayed-speech and substance abuse. Diagnosis of PTSD involves long-term counseling sessions which often tend to get biased owing to the subjective nature of the entire process. Also, patients are often reluctant and unwilling to visit the clinician in-order to avoid confrontation. Diagnostic biological markers, though available for PTSD related factors, are not cost-effective. Further, PTSD has a high disease burden which limits the success of these markers.

A software known as the random forest was developed by researchers which assesses speech patterns for variations in speech, lifeless, metallic tone of the speech along with animated speech using AI. It provided 89% accurate results in the tested participants. The software was fed with data on various speech patterns which it uses as training data to grasp better and provide suitable results. With the use of this preliminary information, clinicians can use naturally collected data for diagnosis of PTSD. This technique, however, is still under research and hopes to aid in the diagnosis of PTSD.

  • Blood Test for Detecting Breast Cancer Relapse

The second most common type of cancer-causing death in women is breast cancer. It can be detected using various methods such as mammography, ultrasound, etc. Although the survival rate has improved in comparison to earlier times, relapse is still a very important concern. Approximately 30% of the patients suffer through a relapse within 5 years. Natera, a genetic testing company has developed a blood test by the name of Signatera, which detects the mutant DNA released by the cancerous cells. The technique, known as Molecular Residual Disease (MRD) Assessment is used for early detection of breast cancer, enabling patients to take proper precautionary measures. This technique was found successful in 89% of relapse cases. The detection, however, has to be clinically confirmed for a confirmed diagnosis. The researchers aim to test this in a large number of the sample population in order to bring this into mainstream diagnostics.

  • New Diagnostic Manufacturing Facility Launches in India

Co-Diagnostics Inc. and Synbiotics Pvt Ltd, together in partnership have launched a diagnostic manufacturing facility in India. It is said to be a one-of-a-kind facility providing state of the art facilities in the world of diagnostics. The owners are known for developing facilities which have global approvals from the leading regulatory bodies (US Food and Drug Administration, World Health Organisation-Good Manufacturing Practices). This facility is not only ready to start operations in India but has plans underway for further expansion. Asence Inc, a US company which specializes in providing pharmaceutical products to various markets, would be managing the commercial operations for the facility.

  • VITROS® XT Chemistry Product Slides (FDA approved)

One factor that delays the diagnosis of various diseases is the delay in lab test results. These diagnostic tests are either time taking or are too many done at one time, which in turn delays the results. Ortho Clinical Diagnostics have come up with a new VITROS® XT MicroSlide which can run two tests simultaneously, thus reducing the time required to conduct these tests along with less usage of the products. Ortho’s VITROS XT MicroSlides, which are available for use on Ortho’s VITROS® XT 7600 Integrated System, provide high-quality results and are used for paired tests such as, triglycerides and cholesterol; urea and creatinine; and glucose and calcium. The miniature testing area in the slide is highly efficient and requires less amount of sample for providing results. With this FDA approved technique (approval received in October 2018), multiple tests can be done together, thus saving time and infrastructure.

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 provides an 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.