News and Media

The World Health Organization (WHO) announced that the viral shedding of the Middle East Respiratory Syndrome (MERS) in South Korea was important, but not a global crisis, reported Reuters the week before. Eight new cases of the disease have been reported in the recent days.

162 people were infected with the virus and 20 people died in the first major viral shedding of MERS outside Saudi Arabia.

The virus came to South Korea after a Korean adult returned from a trip to the Middle East in early May, and the WHO reported an outbreak of new cases was expected, although it seemed that the number of infected people was decreasing.

The members of the emergency committee of the WHO unanimously indicated that MERS in South Korea was not a threat to public health worldwide. Otherwise, coordinated international actions would have had to be organized.
“The problem is of great importance,” said the WHO. “In a world with great mobility the states have to be prepared for the expected possibility of such cases, as well as other serious infectious diseases.”

The organization added that there had been no evidence that the viral shedding was easy and therefore it was not necessary to introduce restrictions on travel to and from the country.

The last eight new cases were more than four and five on the two days before that, while every day the week before that marked more than 10 new cases – the global trend seemed decreasing.

Currently more than 6500 people are under quarantine in South Korea, and the government received criticism for its initial underestimation of the outbreak in the country. “Now all measures to try to stop viral shedding are taken. It is very impressive,” said Keiji Fukida, who was leading the team of the WHO experts, who visited the country last week.

Authorities reported that 19 people diagnosed with MERS, have recovered and have now been discharged from hospitals.

The latest victim of the disease in South Korea was a 54-year-old woman who suffered from bronchiectasis and high blood pressure. Most deaths until now have occurred in people who had pre-existing diseases or elderly people.

All known cases of infection occurred in hospitals. Three hospitals were partially closed and two prohibited medical staff and patients to leave the hospital.

MERS is caused by a coronavirus, similar to the one that led to the worst outbreak of SARS in China in 2003. The majority of infections and deaths have taken place in Saudi Arabia, from 2012 onwards, were more than 1,000 people have been infected, while the victims came to   454.

Referrals will not be necessary for preventive routine examinations starting 2016

Employees are granted one day paid leave every year to undergo preventive medical examinations. The Health Minister Petar Moskov has already held talks with his colleague Ivaylo Kalfin to allow such a change to the Labour Code. This practice exists in all civilized countries like Germany and Sweden, for example. Moskov defended the idea by stating he did not see that Bulgarians were any worse in order to take advantage of such a convenience.

The fine for missing a checkup is BGN 50. However, not a single citizen has been sanctioned.

Starting 2016, when a people went to check their health condition they would not even need a referral from their GP, as every person with healthcare coverage would have an electronic health card. It would hold information about the package of examinations which they were entitled to, Moskov said.

According to him, the division of health services into a basic and additional package would not deprive people of healthcare. The basic package would include all diseases that progress rapidly and could not be put on hold, while the additional package – the ones that could wait, such as cataracts. However, if a person wanted to remove a cataract immediately, they would have to be covered by an additional health insurance fund as well.

At the press conference some days ago the Minister of Health Dr. Peter Moskov stated that at that time the valuation of clinical pathways was like a cat in a bag – no one knew what was in it. He noted that it was unclear how the prices on pathways were formed and what they actually cost. The Minister said he would address a number of issues in that direction – whether the price at that moment ensured a person quality of service, whether the work of doctors was valuated in general, how much went for medical costs, etc.

Dr. Moskov said he was planning to change that and the Ministry was working at that time on the actual evaluation of the activities that would fall into the basic package of health insurance. In his words, it should be clear how much was the actual value of each medical activity, including the funds for the simplest gauze to the most expensive antibiotic. The costs for the use of the equipment and its depreciation would also be taken into account. He said that it was essential to valuate the work of nurses, because at that time that was not calculated in the clinical pathways. Therefore were the planned talks with the BMA where a discussion would be held on how much the average doctors’ salary in the country should be and what were the possibilities to implement the proposals of the professional organizations.

Dr. Moskov said that at that time work was carried out on the evaluation of three disease groups – cancer, cardiovascular and cerebrovascular diseases. He said that the cost of treatment would include all of the above, as well as the cost of consumables.

According to Dr. Moskov such evaluation should be done in relation to the other treatment components – such as the medical devices. He noted that at that moment there was no clarity regarding the basis on which to form their prices and said that would also change. From his words it became clear that the Ministry was preparing a register of products, which would be very different from the current BDA list. A working group would be dealing with this.

The first health reforms initiated by the government are already happening. With the support of the deputies from the parties Patriotic Front and Alternative for Bulgarian Revival last week were adopted conclusive amendments to the Health Insurance Act, which significantly modify the current system of healthcare. Some of them were met with extreme distrust by the opposition politicians who bombarded with criticism the Minister of Health Dr. Petar Moskov, drawing quite apocalyptic results of the innovation. On his part, the Minister explained that the structuring of healthcare, which was at the basis of that law, had existed in many other countries that perform better than Bulgaria, but there had been no apocalypse happening there.

The most serious debate logically flared around the most significant change in the system – the division of the health insurance package into primary and additional. According to the idea of ​​the government, the most socially significant illnesses that cause about 90% of deaths and disability among people are separated in so-called “basic package”. Maternal and child healthcare diseases and conditions also fall into this group. Minister Moscow explained repeatedly to lawmakers and the media that the health indicators of the Bulgarians at that moment had worsened extremely and that we had been at one of the first places in mortality and morbidity negative ratings. He indicated that in order to reverse that trend, it was necessary that health resources were pointed in that direction – both financial and human. From his words it became clear that that was the recommendation of the experts from the World Bank. The Minister ensured that all diseases that fell into that package would be treated quickly and without having the patient pay extra for them. He noted that people had to pay additional sums for the treatment of almost any disease at that moment, regardless whether it was a serious socially significant disease, or could be postponed. Dr. Moscow promised that that would change and that the basic package would include everything concerning socially significant diseases – from the prevention to the treatment of the most severe conditions, where therapy would be performed quickly.

“No person will be sent back in an emergency, and no person with a socially significant disease will be sent back. This is an important thing. For example, cardiovascular diseases will be included the basic package. The way so far: a person goes somewhere, enters am hospital and begins wandering around, paying for all kinds of consumables, paying the doctor and you name whom… The idea is that now we will not be paying,” explained the MP from the party Reformist Bloc, Assoc. Prof. Dimitar Shishkov.

The so called “additional package” is the brainchild of the limited funding of our system. The government holds that with the limited resources available to the Health Fund, the most logical is to look seriously at funding only for the diseases placed in the basic package. In the additional package, for which there is not enough money in the NHIF, fall conditions that can be postponed without jeopardizing patients’ lives or lead to the deterioration of their health. The idea of ​​the ministry here is that for these diseases the Fund will provide money while it has, after which patients will be included in waiting lists or if one does not want to wait, then they should provide for themselves via additional insurance funds.

The packages’ division brought about a number of issues raised mostly by the opposition politicians. One of the most important ones is whether there is patient discrimination because of their right to timely treatment. According to the opposition, there is discrimination, because people are divided into those who can be treated immediately, and those that have to wait. From there, a division between rich and poor was also noticed – the rich will obtain extra coverage, while the poor will have to wait and, as some MPs said some days ago, “to die.”

However, from the various statements made by Dr. Moscow and the MPs from the ruling coalition it became clear that the additional package has two main functions. One is to eliminate cash payments under the table, legalize the already existing at the moment surcharge by the inclusion of insurance funds. The second is linked precisely with the participation of the funds – the creation of the second pillar of health insurance and a gradual shift towards the de-monopolization of the NHIF. According to the ruling coalition, the inclusion of insuring persons is getting prepared for a model change. When this would take place, though, remains unknown.

There have been attacks in the direction that there is still no public information about which diseases would be included in which package and what would the financial impact on the system be. Here, the Minister explained, what was sought was not financial impact – what was sought was a change the health indicators of the Bulgarians in a positive direction. A few days ago he said that the lists of diseases would be ready by October, after which they would be discussed.

Another important aspect of the Health Insurance Act (HIA) changes is connected with the health system financing. There are several texts that modify the current situation. One of them is an attempt to answer the problem of the huge number of uninsured Bulgarians. There is currently no clarity how many they are, although in the public domain there were some numbers, such as 250 000 people, who are able to pay their contributions, but do not wish to do so. Several hundred thousands of poor have been spoken about, who cannot afford to pay, because they have no income. All are theoretically affected by the adopted text, according to which the restoration of health rights will be subject to the payment of contributions for a period covering five years back in time. For those who want to pay their debt to the National Health Insurance Fund by the end of 2015 there was a grace period of 3 years.

According to the government, this measure will greatly enhance the collection of contributions and the Fund will collect additional millions. The reason is that from now on those who are bad payers will be able to use only the emergency package. It is expected that a third package will be created to significantly reduce the number of people who use the emergency services for conditions that are not urgent, as emergency conditions will be determined by clear criteria.

Here the main concerns of the opposition are related to the number of poor, which is too big, and they cannot afford to pay sums exceeding BGN 1,000 that are the due amount for five years back without interest. The problem is compounded by the fact that the number of those whom the state provides for as poor, is not great, and many people remain outside this category.

It is precisely with those whom the state provides for that the next issue, relating to the financing of the system, is connected. The state has managed to escape from its obligation to pay the full fee for the groups of citizens whom it provides for over the next ten years. It currently provides only half of the amount due. It was recorded in the text of the HIA that next year the state will pay 55% of the outstanding 8-percent contribution, and this amount will be increasing by 5% per year until it reaches 100% in 2026

Here is the place to recap that because of the small amounts of money coming into the Fund, the management of the Bulgarian Medical Association, as well as the trade unions, wanted the state to start paying the full coverage as early as next year, or at least only for children. According to their calculations, had the state agreed to pay only for children, it would have provided BGN 300 million extra budget or thereabout for the Fund, as much as the planned deficit for 2015 is.

One of the most important texts proved to be a paragraph where a decision was taken for the NHIF to pay for activities according to the volumes agreed upon in the National Framework Agreement. Here it should be noted that the changes in the HIA returned the practice of negotiating prices and volumes to take place between the Fund on one hand, and the doctors and dentists – on the other. So it becomes absolutely important for the state of the system what prices and volumes will the NHIF and the professional organizations negotiate. Previous years’ experience shows that there are always significant differences between the proposals of the Fund and the doctors, which often leads to the failure to sign an agreement and the adoption of unilateral decisions by the NHIF.

In this sense, it can be assumed that the paragraph in question imposes limits on medical activities through legislation, since the text indicates that the NHIF will only pay the volumes agreed upon. Currently, these limits are imposed by a decree of the Council of Ministers.

There is, of course, the deal between the BMA and the NHIF, that there will be no limitation of the volumes, but prices could be reduced. What happens when this option occurs became apparent a month ago when the NHIF announced it had exceeded volumes and suggested reducing the prices of clinical pathways. After the Doctors’ Union did not agree to that, what is now considered is the transfer of activities and procedures from hospitals to primary care.

The key moment in the future of the healthcare system is linked to another change in the HIA – the NHIF shall be entitled to examine patients’ dissatisfaction and if it proves to be justified – to impose sanctions on medical institutions and even to terminate contracts. The government says the measure would increase the control and quality of the offered services. The reason is that the Fund will have about 2.2 million “controllers” per year – as is the number of hospitalizations. Almost none of the politicians said it was a bad idea, but the remarks of the opposition came from fears it could be used as vigilant justice on some hospitals. According to them, certain patients may get paid to file unfounded complaints. They hold that this could lead to deliberate vigilant justice exercised by the Fund or government hospitals in dealing with disobedient hospitals or those designated to be privatized. It was noted that there was a lack of clarity regarding the criteria for dissatisfaction because the Ministry of Health had yet to determine them.

The ruling coalition responded by pointing out that the termination of contracts would be a punitive measure for serious violations and would be made after a certain number of complaints came in. At the same time the MPs agreed that before reaching the final sanction there would be financial penalties, depending on the seriousness of the offense.

The changes in the HIA are essential for the healthcare future in our country. The government argued that they were dictated by the World Bank and imposing a new model that already exists in the European countries with the best healthcare. Concerns about how some of the changes will fit into our current reality and whether they can change certain negative practices still remain. Especially in the conditions of a political war between the government and the opposition, the war field unfortunately being the healthcare in the years to come.

Metformin is the most commonly used anti-diabetic medicine worldwide. It is generally recognized by experts as the first choice diabetic glucose-lowering drug for glycemic diabetes type 2 (DT2) control – the preferred tool for starting pharmacotherapy according to the international guidelines (the European Association for the Study of Diabetes, the American Diabetes Association and the International Diabetes Federation) and the national standards.

Metformin is associated with beneficial effects, including with increasing life expectancy, improving the cardiovascular outcomes or even preventing the onset of certain cancers.

Metformin reduces hyperglycaemia by mainly suppressing hepatic glucose production (hepatic gluconeogenesis), by the activation of the enzyme adenosine monophosphate-activated protein kinase (AMPK).

Other molecular mechanisms that may play a role for the glucose-lowering effect of this drug are: the inhibition of the mitochondrial respiratory chain; the inhibition of the glucagon-induced increase of cyclic adenosine monophosphate (cAMP) and the subsequent activation of protein kinase A (PKA); the activation of the intestinal flora (microbiota) and increased levels of total and intact glucagon-like peptide-1 (GLP-1).
Evidence that metformin is very effective as monotherapy for improving HbA1s dates from 1995. DeFronzo and his colleagues conducted two large randomized, double-blind, parallel group studies in patients with moderate obesity and DT2, who had not achieved good glycemic control with diet alone, and showed that metformin was superior to:

– Placebo, when improving the levels of fasting plasma glucose – FPG (10.6 +/- 0.3, respectively, as compared to 13.7 +/- 0.3 mmol / l) and HbA1c (7.1 +/- 0.1 as compared to 8.6 +/- 0.2%);
– the Sulfonylurea agent glibenclamide, for improving the levels of FPG (10.5 +/- 0.2 as compared to 14.6 +/- 0.2 mmol / l) and HbA1c (7.1 +/- 0.1 as compared to 8.7 +/- 0.1%) but at a low incidence of hypoglycemia.
Moreover, patients treated with metformin demonstrated a statistically significant reduction in the plasma levels of total cholesterol, LDL-cholesterol and triglycerides, while in the other two subgroups no changes were observed.

Metformin maintains lasting control in time, as compared to sulfonylurea agents, applied in both cases as monotherapy (the cumulative rate of depletion of the action for a period of five years – 21% vs. 34%), as the survey data of ADOPT (A Diabetes Outcome Progression Trial), published in 2006 indicated.

Metformin alone can maintain the glycemic control in patients with DT2 at a significantly lower incidence of hypoglycaemia for a long time, as compared to sulfonylurea agents – which is another important conclusion from the study.

The intensive glycemic control with metformin, used as first-line therapy, resulted in a lower incidence of all diabetes-related adverse outcomes, including diabetes-related death in patients with DT2 and obesity, indicated the UKPDS (UK Prospective Diabetes Study) survey data.
Moreover, metformin is associated with a much lower risk for hypoglycemia and has a neutral effect on weight, unlike the sulfonylurea agents CC (+2.3 kg) and insulin (+4.5 kg). The authors of the UKPDS recommend the use metformin as a pharmacological first choice therapy for patients with DT2 and obesity.

There was a decrease of 32% of all diabetes-related outcomes, 42% – of diabetes-related mortality, 36% – of total mortality, 39% – of myocardial infarction and 50% – of deaths from coronary heart disease in patients treated with metformin, as compared to the group on conventional glycemic diet control alone.

In patients on intensive glycemic control, metformin achieved a better effect than the sulfonylurea agents or insulin to lower the incidence of all diabetes-related outcomes, of overall mortality and stroke. In the study HOME, the therapy with metformin resulted in weight loss (-3 kg) and lower insulin needs. The administration of this drug for an average of 4.3 years has led to a reduction in macrovascular events (secondary endpoint) by 39%, confirming the results from the UKPDS.

Retrospective observational studies suggest an increased cardiovascular events and deaths risk associated with sulfonylurea agents, as compared to metformin, used in both cases as an initial monotherapy in patients with DT2. A retrospective analysis of the UK Clinical Practice Research Datalink (CPRD) for the period 2000-2012, compared initial monotherapy with metformin to that with sulfonylurea agents. It indicated that sulfonylurea agents are linked to 1.58 times higher total mortality than biguanide. These data support the idea that metformin should be the first choice for DT2 treatment.

The analysis included the data of 78,241 people treated with metformin, 12 222 patients treated with sulfonylurea agents and 90 463 controls without diabetes, who had similar demographic characteristics, smoking history, health status, and were monitored by the same GP.

A total of 7498 cases were fatal, as the mortality rate reached 14.4 (for those on monotherapy with metformin) and 15.2 (in the corresponding controls) to 50.9 (for those on monotherapy with sulfonylurea agents) and 28.7 (in the corresponding controls) per 1000 patient-years.

Metformin may slow down the development of DT2

The study DPP (Diabetes Prevention Program) found that metformin (850 mg twice daily) as compared to placebo may decrease the risk of the onset of DT2 by 31% over three years in patients with a pre-diabetic condition. The benefits of this preventive intervention are particularly pronounced in younger obese patients.

During the extension phase (the DPPOS- Diabetes Prevention Program Outcomes Study), which lasted for a period of 12 years after the DPP, in the group receiving metformin treatment during the DPP / DPPOS, the risk of DT2 development remained lower by 18% than in the placebo control group during the DPP, although both groups took measures to change their lifestyle.

The authors of the DPPOS drew an important conclusion – that delaying the onset of DT2 via introducing a lifestyle change (the more efficient method) or by taking metformin, or by using both methods, may protect people with pre-diabetes conditions from the onset of DT2 and the related microvascular complications (-28% lower frequency compared to the patients who developed DT2). The results of the DPP / DPPOS show that the treatment with metformin leads to mild, but long-term weight loss, as this seems to be the main factor that slows the development of DT2.

For a period over 15 years biguanidine has demonstrated an excellent safety profile and tolerability. A particularly valuable advantage of metformin is the very low risk of hypoglycaemia. Patients who have suffered through one or more episodes of severe hypoglycemia, associated with glucose-lowering therapy, have a higher likelihood of cardiovascular events (myocardial infarction or ischemic stroke) and increased mortality (cardiovascular and all-cause), showed the results of the studies ADVANCE ( Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) and ORIGIN (Outcomes Reduction with an Initial Glargine Intervention).

Therefore, the prescription of agents that can cause hypoglycemia should be done only when absolutely necessary and after careful consideration. An advantage should be given to antidiabetic drugs that are associated with a minimal risk of hypoglycemia.

Opinion on the control of hyperglycemia in DM type 2

In 2012, the American Diabetes Association and the European Association for the Study of Diabetes produced an Opinion on the control of hyperglycemia in DM type 2, and in 2015 they published a second updated option. According to this opinion, the first step in the treatment of DM type 2 is a change in lifestyle and monotherapy with metformin. If in three months’ time the individual glycemic targets have not been reached, a switch is made to two drugs combination therapy, and upon its failure in another three months – a third medicine is added to the therapy.

Few therapeutic agents intended for the treatment of diabetes type 2 have an effective impact both – insulin resistance, and the function of the beta-cells, when administered as monotherapy. Another drug which enhances insulin sensitivity and improves the function of beta cells apart from metformin is pioglitazone (from the group of the thiazolidinediones). Pioglitazone appears to have an even more pronounced positive effect on beta-cells. These characteristics of both medicines make them suitable combination for initial or additional therapy in patients who cannot achieve good glycemic control.

In comparative/combined studies with metformin, pioglitazone showed equal efficacy in terms of the reduction of glycated hemoglobin and fasting plasma glucose with continuous monitoring. The combination therapy with metformin and pioglitazone had a synergistic effect, leading to significant improvements in glycemic control, as well as an increase in HDL-cholesterol and a decrease in triglycerides, as compared to metformin and placebo.

To sum up:

1. First-line therapy – metformin;
2. Second line therapy – adding sulfonylurea agents to metformin;
3. Third-line therapy – the replacement of sulfonylurea agents/metformin or adding pioglitazone, sitagliptin, vildagliptin, at the choice of the physician. Data from clinical trials showed that the addition of pioglitazone reduced HbA1c to a greater degree than sitagliptin and vildagliptin (Chawla et al., 2013, Liu et al., 2013, Lee et al., 2013, Bolli et al., 2008, Kaur M. et al., 2014, Kaur K. et al., 2014);
4. Fourth-line therapy – exenatide is added to metformin or sulfonylurea agents only when the BMI> 35,0 kg / m².

Tchaikapharma High Quality Medicines Inc. offers the following medicines for the treatment of DM type 2 on the Bulgarian market:

NHIF code – AF 341 – Metformin-Tchaikapharma (metformine)

850 mg x 30 tablets – does not require extra pay

NHIF code – AF 505 – Pizona (pioglitazone)

15 mg x 30 tablets – does not require extra pay

NHIF code –  AF 506 – Pizona (pioglitazone)

30 mg x 30 tablets – does not require extra pay

NHIF code –  AF 507 – Pizona (pioglitazone)

45 mg x 30 tablets – does not require extra pay