Policies and measures implemented to reduce the impact of international sanctions on Iran's pharmaceutical sector.

Background and purpose: Continuous evaluation of the policies and interventions could explore their efficacies in improving the accessibility and availability of medicines in the local market. This study explained the health system policies of the Islamic Republic of Iran concerning the impact of the economic sanctions on the local pharmaceutical market and addressed the issue of whether these policies were able to improve patients' access to medicines. Experimental approach: In this study, qualitative and quantitative research methods were used. In the qualitative part, semi-structured interviews with pharmaceutical system experts were used. In the next step, the structural analysis method was used. In the quantitative part, numerical sales data of the selected medicines were extracted and analyzed. Findings/Results: Reported statistics regarding the presence of the medicines in the market indicates the obvious fluctuations in the numerical sales of medicines in the studied years. This may indicate that the policies implemented are not able to fully compensate for the negative effects of sanctions and improve access to medicine. In addition, according to some experts, policy, and management weaknesses are mainly rooted in unresolved domestic hurdles which have exacerbated the effects of international sanctions on the country's pharmaceutical market. Conclusions and implications: Effective policy-making in response to economic sanctions can reduce the negative effect of international sanctions and result in drug shortages. Results of this study showed despite efforts made by the Iran health sector to subside the impact of sanctions on the pharmaceutical sector, there is an obvious disruption of the medicine supply chain in the market.

The Association of Age, Sex, and RT-PCR Results with the Lymphocyte and Neutrophil Counts in SARS-CoV-2 Infection: A Cross-sectional Analysis of 1450 Iranian Patients with COVID-19.

Containment of pandemic infections mainly depends on prompt identification of carriers, achievable through strict surveillance and truthful diagnostic testing. Although molecular identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard method, its low sensitivity and long turnaround time are among major concerns. In this retrospective single-center study, we reviewed the results of the lymphocyte and neutrophil counts of 1450 Iranian patients with coronavirus disease 2019 (COVID-19) recruited at Baqiyatallah Hospital, Tehran, Iran. Of 1450 patients, 439 cases (30.3%) were polymerase chain reaction (PCR) negative; further emphasizing that getting negative molecular testing is not as reliable as a positive result. While the lymphocyte count in cases with less than 50 years old was 1.8×103/µL (1.2-2.5), it was 1.47×103/µL (0.84-2.16) in the older group (p<0.001). Also, men experienced lower lymphocytes as compared to women (1.53×103/µL vs 1.76×103/µL; p=0.002). Of particular interest, the lymphocyte count in the PCR-negative cases was 1.77×103/µL (0.98-2.45) which was significantly higher than its count in their positive counterparts (1.53×103/µL; p=0.004). Unlike lymphocytes, sex and PCR did not significantly affect the number of neutrophils. The odds ratio for neutrophilia in patients aged older than 50, either with a negative or a positive PCR, was 2.46 and 2.23, suggesting old age as the most significant associated factor. The number of lymphocytes along with increased neutrophil count may probably serve as simple, rapid, and economical biomarkers, and are seemingly appropriate items that should be taken into account in the identification of patients with COVID-19, especially those aged more than 50.

Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: Results of a multicenter clinical study.

Since Dec. 2019 the new coronavirus (SARS-CoV-2) has infected millions and claimed life of several hundred thousand worldwide. However, so far no approved vaccine or drug therapy is available for treatment of virus infection. Convalescent plasma has been considered a potential modality for COVID-19 infection. One hundred eighty-nine COVID-19 positive patients including 115 patients in plasma therapy group and 74 patients in control group, registered in the hospitals with confirmed COVID-19 infection, entered this multi-center clinical study. Comparison of outcomes including all-cause mortality, total hospitalization days and patients' need for intubation between the two patient groups shows that total of 98 (98.2 %) of patients who received convalescent plasma were discharged from hospital which is substantially higher compared to 56 (78.7 %) patients in control group. Length of hospitalization days was significantly lower (9.54 days) in convalescent plasma group compared with that of control group (12.88 days). Only 8 patients (7%) in convalescent plasma group required intubation while that was 20 % in control group. This clinical study provides strong evidence to support the efficacy of convalescent plasma therapy in COVID-19 patients and recommends this treatment for management of these patients. Clinical efficacy, immediate availability and potential cost effectiveness could be considered as main advantages of convalescent plasma therapy.

Management of COVID-19 Virus Infection by Convalescent Plasma.

No Abstract.

Gentamicin-Loaded Chitosan Nanoparticles Improve Its Therapeutic Effects on Brucella-Infected J774A.1 Murine Cells.

BACKGROUND: Final elimination of some intracellular bacterial agents, such as Brucella, is often a complex issue and impossible to achieve, primarily due to the presence and survival of the bacteria within phagocytic cells. By penetrating into the cell membrane, drug delivery nanosystems can reduce the number of intracellular bacteria. The aim of this study was to assess the efficacy of chitosan nanoparticles on the delivery of gentamicin into Brucella infected J774A.1 murine cells in vitro. MATERIALS AND METHODS: Chitosan nanoparticles (NPs) were synthesized using ionic gelation technique. The shape, size and charge of NPs, loading rate and release of the drug were investigated. Finally, the effects of gentamicin-loaded chitosan NPs (Gen-Cs) and free gentamicin on J774A.1 murine cells infected with these bacteria were examined. RESULTS: The mean size and charge of NPs were computed as 100 nm and +28mV, respectively. The loading capacity of NPs was 22%. About 70% of the drug was released from NPs during the first 8 hours. Antimicrobial activity of the two formulations showed that MIC (minimum inhibitory concentration) of the Gen-Cs and free drug was 3.1 and 6.25 µg, respectively. The minimum bactericidal concentration of the NPs-loaded drug and free drug was 6.25 and 12.5 µg, respectively. Cell culture analysis revealed that there was a significant reduction in the load of the intercellular bacteria in J774A.1 murine cells in both formulations. CONCLUSION: Our results showed the Gen-Cs have a proper potential for optimal treatment of intracellular bacterial agents.

Impact of economic sanctions on access to noncommunicable diseases medicines in the Islamic Republic of Iran.

BACKGROUND: It has been argued that economic sanctions and the economic crisis have adversely affected access to drugs. AIM: To assess the impact of economic sanctions on the Iranian banking system in 2011 and Central Bank in 2012 on access to and use of drugs for noncommunicable diseases (NCDs). METHODS: An interrupted time series study assessed the effects of sanctions on drugs for diabetes (5 drug groups), asthma (5 drug groups), cancer (14 drugs) and multiple sclerosis (2 drugs). We extracted data from national reference databases on the list of drugs on the Iranian pharmaceutical market before 2011 for each selected NCD and their monthly sales. For cancer drugs, we used stratified random sampling by volume and value of sales, and source of supply (domestic or imported). Data were analysed monthly from 2008 to 2013. RESULTS: Market availability of 13 of 26 drugs was significantly reduced. Ten other drugs showed nonsignificant reductions in their market availability. Interferon α2b usage reduced from 0.014 defined daily doses per 1000 inhabitants per day (DID) in 2010 to 0.008 in 2013; and cytarabine from 1.40 mg per 1000 population per day in 2010 to 0.96 in 2013. Selective ß2-adrenoreceptor agonists usage reduced from 8.4 to 6.8 DID in the same time period. CONCLUSION: There is strong evidence that sanctions have had a negative effect on access to drugs, particularly those that depended on the import of their raw material or finished products.

Health-Related Quality of Life and Health Utility Values in Beta Thalassemia Major Patients Receiving Different Types of Iron Chelators in Iran.

Background: Thalassemia is a chronic, inherited blood disorder, which in its most severe form, causes life-threatening anemia. Thalassemia patients not only engage with difficulties of blood transfusion and iron chelating therapy but also have some social challenges and health threatening factors. There are some reports on quality of life in thalassemia patients around the world from southeast of Asia to Italy in Europe and United States. In this study, we tried to evaluate and compare Health Related Quality of life (HRQoL) and the health utility in beta thalassemia major patients receiving different types of iron chelators and living in different socio-economical situations. Subjects and Methods: EQ-5D-3L accompanied by a Visual Analogue Scale (VAS) questionnaire was used. The respondents were patients with beta thalassemia major that were at least 12 years old selected from 3 provinces of Sistan-Blouchestan, Fars and Mazandaran. Comorbidities including heart complication, Diabetes Mellitus and Hepatitis and also types of iron chelators (oral, injection, combination of both) were also asked. Cross tab and ANOVA analysis conducted to evaluate each dimension score and health utility differences between provinces, iron chelation methods, comorbidities, age group and gender. Results: 528 patients answered the questionnaires. The health utility of patients that received oral iron chelator were 0.87 ± .01 for oral iron chelators versus 0.81 ± .01 for injection dosage form (p<0.05). Increase in age was accompanied by decrease in health utility. Females faced more usual activity problems, anxiety and depression. Heart problems were more prevalent in males. Conclusion: This study suggests that the quality of life of beta thalassemia major patients is dependent on type of iron chelation treatment which they received, the gender they have, the comorbidities they suffer and socio-economical situations they live in.

Evaluation of prescriptions of medicines not included in Iran medicine list: A cross-sectional study.

OBJECTIVE: Iran Food and Drug Administration (IFDA) has the mission to regulate all aspects of pharmaceutical market including registration of the new medicines. Iran Drug Selection Committee has the responsibility to maintain and revise Iran Medicine List (IML). The National law has banned production, importation, distribution, and prescription of medicines not included in IML. Although, IFDA policy makers have created a mechanism to provide medicines not included in the list but might be essential for the treatment of specific patients. METHODS: A cross-sectional study was carried out on prescription of out of IML medicines during the year 2015. This study was conducted on a total of 1375 application forms received by Secretariat of Iran Drug Selection Committee for prescription of out of IML medicines. FINDINGS: It has been shown that among 402 specialist physicians, the most out of IML medicine were prescribed by oncologist/hematologist. Antineoplastic and immunomodulating agents were the most frequently prescribed medicines both in terms of number and diversity. According to the collected data, more than 76% of all medicines were supplied by only 4 out of 25 pharmaceutical companies in 1 year. CONCLUSION: Results of this study show that despite its early intention this mechanism is easily abused by some pharmaceutical companies as an unethical way of induced demand and marketing of their products. Therefore, IFDA decision makers should revise this mechanism and decide based on its real benefits and harms both to the patients and Iran national health system.

A review of pharmaceutical policies in response to economic crises and sanctions.

An economic crisis has been defined as a situation in which the scale of a country's economy becomes smaller in a period of time. Economic crises happen for various reasons, including economic sanctions. Economic crises in a country may affect national priorities for investment and expenditure and reduce available resources, and hence may affect the health care sector including access to medicines. We reviewed the pharmaceutical policies that the countries adopted in order to mitigate the potential negative effects on access to medicines. We reviewed published reports and articles after conducting a comprehensive search of the PubMed and the Google Scholar. After extracting relevant data from the identified articles, we used the World Health Organization (WHO) access to medicines framework as a guide for the categorization of the policies. We identified a total of 40 studies, of which 10 reported the national pharmaceutical policies adopted to reduce the negative impacts of economic crises on access to medicines in high-income and middle-income countries. We identified 89 policies adopted in the 11 countries and categorized them into 12 distinct policy directions. Most of the policies focused on financial aspects of the pharmaceutical sector. In some cases, countries adopted policies that potentially had negative effects on access to medicines. Only Italy had adopted policies encompassing all four accesses to medicine factors recommended by the WHO. While the countries have adopted many seemingly effective policies, little evidence exists on the effectiveness of these policies to improve access to medicines at a time of an economic crisis.

Evaluation of heavy metals contamination in Iranian foodstuffs: canned tomato paste and tomato sauce (ketchup).

One hundred and thirty-five samples of canned tomato paste and 30 tomato sauces (ketchup) samples (23 and 10 brands, respectively) purchased from wholesale markets in the Tehran, Iran, during the period 2010-2013 were analysed. Levels of lead and cadmium were determined by graphite furnace atomic absorption spectrophotometer (GF-AAS) and arsenic by hydride vapour generation (HG-AAS or VGA). Average concentration of arsenic found in the tomato paste and ketchup samples was 62 ± 14 and 48 ± 12 ng g(-1), respectively. Cadmium values in 7% of tomato paste and 10% of ketchup samples were below the limit of quantification (LOQ). Lead concentrations were below LOQ in 75% of tomato paste and 77% of ketchup samples. Values obtained for these heavy metals in all samples were lower than the limits of national and international standards.

A system dynamics model for national drug policy.

BACKGROUND: Data modeling techniques can create a virtual world to analyze decision systems. National drug authorities can use such techniques to take care of their deficiencies in decision making processes. This study was designed to build a system dynamics model to simulate the effects of market mix variables (5 P's) on the national drug policy (NDP) indicators including availability, affordability, quality, and rationality. This was aimed to investigate how to increase the rationality of decision making, evaluate different alternatives, reduce the costs and identify the system obstacles.System dynamics is a computer-based approach for analyzing and designing complex systems over time. In this study the cognitive casualty map was developed to make a concept about the system then the stock-flow model was set up based on the market demand and supply concept. RESULTS: The model demonstrates the interdependencies between the NDP variables through four cognitive maps. Some issues in availability, willingness to pay, rational use and quality of medicines are pointed in the model. The stock-flow diagram shows how the demand for a medicine is formed and how it is responded through NDP objectives. The effects of changing variables on the other NDP variables can be studied after running the stock-flow model. CONCLUSION: The model can initiate a fundamental structure for analyzing NDP. The conceptual model made a cognitive map to show many causes' and effects' trees and reveals some relations between NDP variables that are usually forgotten in the medicines affairs. The model also provides an opportunity to be expanded with more details on a specific disease for better policy making about medication.

Comparison of bypassing agents in bleeding reduction in treatment of bleeding episodes in patients with haemophilia and inhibitors.

CONTEXT: Mild-to-moderate bleeding disorders in haemophilia are primarily treated via recombinant activated factor VII a (rFVIIa) or activated prothrombin complex concentrate (aPCC). However, the efficacy of each bypassing agents may vary and none of them is universally effective. EVIDENCE ACQUISITION: After reviewing the databases of PubMed, Scopus, MD Consult, Ovid, Trip database, Google Scholar, ProQuest and the Cochrane Library, finally, 17 papers published from 2000 to 2013 were extracted. We used as a random effect model in meta-analysis. Comprehensive meta-analysis (CMA) software was used for calculating and estimating the mean of bleeding reduction and performing meta-analysis. RESULTS: The mean of bleeding reduction in aPCC and rFVIIa were 71.2% with CI 95% (lower limit 86.8% and upper limit 82%) and 72.3% with CI 95% (lower limit 57.6% and upper limit 83.4%), respectively. CONCLUSIONS: Although differences between the two products were very close to each other, they reported similar effects on joint bleeds. Further clinical studies should be performed by incorporating a standardized measurement in comparative efficacy of aPCC and rFVIIa.

Impacts of international sanctions on Iranian pharmaceutical market.

Iran in recent decade faced several regional and international sanctions in foreign trade, financial and banking services. Iran national pharmaceutical industry has always played a major role in providing medicines to the Iranian patients. However, following the sanctions it has faced profound difficulties for importing of both finished products and pharmaceutical raw materials. Although medicines are exempted from sanctions, due to restriction on money transaction and proper insurance Iranian pharmaceutical companies have to pay cash in advance for imports of medicines and raw materials or to secure offshore funds at very high risks. Current situation in Iran pharmaceutical market confirms that the sanctions against Iran are affecting ordinary citizens and national health sector which resulted to reduction of availability of lifesaving medicines in the local market and has caused increasing pain and suffering for Iranian patients.

Cost effectiveness of Iran national plasma contract fractionation program.

Plasma derived medicines (PDM) including immunoglobulins, clotting factors and albumin are life saving medicines which due to their high costs are inaccessible for many patients living in developing countries. By contrary substantial volume of plasma as raw materials for production of these medicines are discarded worldwide. Good quality recovered plasma, as a result of separation of donated blood into its components, could be used for production of PDM. In 2011 Iranian donors donated about 2 million units of blood. A shift from administration of whole blood to components therapy has resulted in the generation of over 250,000 liters of surplus of recovered plasma. This created a good opportunity for Iran's health care system to use this plasma for production of PDM. Therefore Iran national transfusion service has started a contract fractionation program for converting recovered plasma into PDM. This program not only provided essential PDM for Iran pharmaceutical market but also has created a direct saving of about 8.5 million Euros in 2011 for national health sector. In addition this program has drastically contributed to improvement of overall quality of working procedures and services provided by Iran national blood transfusion organization.

Cost Assessment of Implementation of Immune Tolerance Induction in Iran.

OBJECTIVE: A number of hemophilia A patients who receive clotting factors may develop antibodies (inhibitors) against clotting factors. The immune tolerance induction (ITI) method has proved to be a very cost-effective alternative to bypassing agents. Iran's national health authority is interested in implementing the ITI method for the management of hemophilia patients with inhibitors. The objective of this study was to calculate the breakeven point between costs attributed to the ITI method and the use of bypassing agents for the management of high-responder hemophilia patients with inhibitors. METHODS: This study assessed costs attributed to the implementation of ITI for the management of Iranian hemophilia patients with costs of high-titer and high-responding inhibitors from the perspective of the national health system. The main objective was to find the breakeven point for the ITI method in comparison with the use of bypassing medicine, recombinant factor VIIa (Novoseven). RESULTS: Based on the sensitivity analysis performed, the breakeven point mainly depends on costs of factor VIII, Novoseven, and the success rate of the ITI intervention. According to this analysis, the breakeven point of ITI and Novoseven methods varies between 16 and 34 months posttreatment. The optimized point is about 17 months posttreatment. CONCLUSIONS: Iran's national health system spends more than 24 million euros for providing bypassing agents to about 124 hemophilia patients with inhibitors. Because of limited resources available in Iran's health sector, this is a huge burden. Results of this study show that the implementation of the ITI method for the management of Iranian hemophilia patients with inhibitors is a cost-saving method and Iran's health system will recover all the expenditure related to the implementation of ITI in less than 2 years and will make a considerable saving along with providing standard care for these patients.

Blood safety concerns in the Eastern Mediterranean region.

Blood transfusion is a life-saving component of health care systems. Nevertheless, it can also be a quick and easy method of exposing patients to risks, particularly the transmission of infectious agents to recipients. Despite substantial improvements in the safety of transfusion services worldwide, the presence of paid and replacement blood donors are still of cause concern for ensuring sustainable safe blood donations. Although the Eastern Mediterranean region consists of a heterogeneous group of countries that vary in their levels of development, they all share common concerns regarding blood safety. In the region, concerns regarding the spread of Hepatitis B and C through blood transfusion continue to exist. Therefore, there is an urgent need for further improvements in both organization and safety measures of blood transfusion activities in the region. Although establishing a centralized blood transfusion system might not be achievable in the short term in some of the countries in the region, the implementation of centralized test kit procurement, data collection, and donation testing could be considered feasible approaches.

Improving availability and affordability of plasma-derived medicines.

Plasma contains several therapeutically important proteins. Currently more than 25 of them are commercially available to treat life-threatening diseases. Some of these medicines already included in the WHO Model List of Essential Medicines indicating their importance from a global perspective. However, unfortunately due to very high cost of treatment with plasma-derived medicines, these clinically precious tools are not affordable for a majority of the patients living in developing countries. There are some options available for securing accessibility to these medicines. These include local production, importation and contract fractionation of locally produced plasma. Although local production of plasma-derived medicines and/or importation of these medicines might be a practical approach to respond to the needs for these medicines, in recent years several countries have used contract fractionation of locally produced plasma as a very effective approach for improving availability and affordability of plasma-derived medicines in their national market.