Cheaper Medicines Research Articles

Screening of bacteria isolates from earthworm cast for antibacterial activities

The healthy operation of the soil ecosystem is significantly influenced by earthworms. Various medical treatments have included the use of earthworms. This study isolated and screened bacterial species from earthworm cast for antibacterial activities. Two (2) bacteria species were isolated from the earthworm cast by culturing on starch casein agar using pour plate techniques. The isolates were identified as Streptomyces and Actinomadura species while the test isolates include Klebsiella specie, Salmonella shigella and Staphylococcus aureus strains. This study revealed that Streptococcus and Actinomadura metabolite exhibited variable degrees of antimicrobial activities against the test isolates. The highest in-vitro antimicrobial activity is (12.0mm) was exhibited by the Streptococcus metabolite at the highest concentration of 100mg/ml against Staphylococcus aureus, while the least antimicrobial activity (8.0mm) was exhibited at the concentration of 80mg/ml and 40mg/ml against Salmonella species and Staphylococcus aureus. Actinomadura metabolite was effective against Staphylococcus aureus at the highest concentration of 100mg/ml. However there was significant difference observed in antibacterial activity of the metabolites when compared to the standard antibiotic (Gentamicin) (p<0.05). From the minimum inhibitory concentration (MIC) test result, Streptococcus metabolite demonstrated greater activity on Salmonella specie at the range of 3.12mg/ml and a lower activity on Staphylococcus aureus and Klebsiella specie at the range of 12.5mg/ml each. The Actinomadura metabolite demonstrated greater activity on Salmonella species at the range of 1.56mg/ml. Based on the findings of this research, earthworm (Pheretima posthuma) is a good source of antibacterial agents that can be identified and extracted as source of cheap medicines to control serious infections.

The silent epidemic of substandard and falsified medicines in low- and middle-income countries: heed lessons from the tragic deaths of children in Indonesia

The silent epidemic of substandard and falsified medicines in low- and middle-income countries: heed lessons from the tragic deaths of children in Indonesia

Comparing the Effect of Local Application of Peppermint and Cold Compresses on the Severity of Pain from Venipuncture in Dialysis Patients: A Parallel Randomized Clinical Trial Study.

Pain at the injection site is one of the most common complaints in the clinic and is the most important symptom affecting the quality of life of hemodialysis (HD) patients. The aim of this study was to determine the effect and compare the topical application of peppermint and cold compresses on the intensity of pain caused by the insertion of a needle into the fistula of HD patients. In this parallel randomized clinical trial, 99 HD patients were assigned to three groups receiving peppermint, a cold compress, or a control using six blocks. For the peppermint group, 20 min before the needle's insertion, a peppermint gel was used; for the cold compress group, an ice pack was used; and for the control group, the usual method was applied. The patients' pain was assessed with the Visual Analog Scale immediately after the needle's insertion. The results showed that after the intervention, the mean and standard deviation of the pain score in the intervention groups receiving peppermint (4.81 ± 1.13) or a cold compress (4.78 ± 1.13) were significantly less than those of the control group (8.42 ± 1.22) (P <0.001), but there was no statistically significant difference between the peppermint group and the cold compress group (P = 0.91). The use of peppermint, which is a cheap and uncomplicated herbal medicine, and a cold compress, which is easy to use and available, is recommended to reduce the severity of pain caused by venipuncture in HD patients.

АHOLINI DORI VOSITАLАRI BILАN TА’MINLАSHNING NAZARIY-HUQUQIY ASOSLARI

The peculiarities of regulating legal relations concerning the provision of free medical care to the population and their social security means are manifested in the norms of branches of social security law of administrative law. One of the additional elements of providing citizens with free medical care is medicines. All the legislation of our country in the field of medicines provides social protection to the population by supplying cheap and high-quality medicines to a wide range of citizens and contributing to a narrow circle of certain categories of citizens with medicines on a free or partial basis. Although the mechanisms of drug provision to the population are fixed by legal norms, the theoretical and scientific foundations of the inseparable connection between the concepts of social security and drug provision have not been studied. The subject of the article is national and foreign legislation in the field of drug provision, as well as the research work of scientists. During the research, such methods as historicism, system analysis, comparative-legal, logical, generalizing, complex analysis of scientific sources were used. Based on the results of the research work, a general conclusion was drawn and proposals were developed to introduce the concept of “drug provision” into the relevant legislation and give it a legal definition.

PEMBERDAYAAN IBU-IBU PKK DALAM MENGEMBANGKAN TANAMAN APOTEK HIDUP DI KELURAHAN SUKABUMI UTARA, JAKARTA BARAT

This research focuses on empowering PKK, especially women in North Sukabumi Village, Kebon Jeruk, West Jakarta. A live pharmacy is an activity to use part of the land to plant medicinal plants for daily needs with the aim of helping people who have diseases and slowly shifting medical treatment to herbal medicines. Live apothecary plants are types of plants that are useful for health and beauty. Efforts to improve public health need to be continued to realize the welfare of the community which is still diverse. The method used in this research is a qualitative approach with data collection techniques based on field studies in the form of observations and interviews with 3 stages, starting with the preparation stage, then the implementation stage and closing with the report stage. Community empowerment is carried out through outreach activities or counseling about the importance of using medicinal plants for family life in the hope of helping the community in getting cheap medicines that can be formulated by themselves without worrying about side effects that are harmful to health.

Colchicine for Coronary Artery Disease: A Review

Coronary artery disease is a serious threat to human health. More and more evidences indicate chronic inflammatory plays a key role in the development of this disease. Inflammation markers are gradually used in the diagnosis and treatment. Although the treatment of coronary heart disease with colchicine is still controversial, more and more studies showed that patients can benefit from this medicine. In this review, we discuss and summarize colchicine on essential pharmacology, anti-inflammatory mechanism of action, and the most important and recent clinical studies. According to these literatures, colchicine possibly will possibly become a new valuable and cheap medicine for the treatment of coronary artery disease.

Endless Run Based Medicinal Plant Educational Game Development

Medicinal plants are very beneficial for health. Medicinal plants can be used as an alternative to cheap and efficient medicine, but not everyone knows what plants can be used as medicine and how to process them. Students are expected to be more familiar with the types of medicinal plants, both local and scientific names, uses, parts used, processing methods, and rules for use. To be able to introduce medicinal plants more interactively, then one solution that can be applied is through application-based games. Educational games are expected to stimulate students to be more active in studying medicinal plants. The game technique used is endless run. Game "Endless Run" is categorized as an action game, has a linear design without ending, without stopping and no stages or changing levels. "Endless Run" is a game where the main character in the game continues to run the game that will not stop. The results of the usability trials shown to teachers, lecturers and students showed good respondents so that people who want to learn the introduction of medicinal plants can obtain information and benefits so that they can increase students' learning desires and the application is easy to operate and the survey results from the percentage (effect 80 %, control 90%, efficiency 70%, helpfulness 80%, learnability 90%). The Endless Run-Based Medicinal Plant Educational Game Development Application can be used by students, college students, millennials and the general public. By utilizing the Unity 3D application, this software includes a game engine capable of handling three-dimensional graphics. This application will run on the Android 8.0 (Oreo) mobile platform with an application capacity of 33.37MB.

International Academy of Perinatal Medicine (IAPM) guidelines for screening, prediction, prevention and management of pre-eclampsia to reduce maternal mortality in developing countries.

Approximately 800 women die from pregnancy or childbirth-related complications around the world every day, 99% of which occur in developing countries. In majority of cases deaths are related to pre-eclampsia and eclampsia. The purpose of new adjusted and simplified IAPM guidelines is specifically lowering maternal mortality by decreasing preventable deaths in developing countries (particularly in remote rural areas) by using rather cheapmedicines used to control chronic and gestational hypertension, prevent pre-eclampsia in high-risk pregnancies and treat severe pre-eclampsia and eclampsia. IAPM guidelines should be implemented and evaluated ineach developing country respecting specific problems, needs and resources. It is of essential importance to: 1.Identify specific high-risk pregnancies, 2. Commence timely appropriate ASA and calcium supplementation, 3.Organize basic antenatal care and adequate referral of pregnancies with early onset of pre-eclampsia to the appropriate institutions and ensure induction of labour inwell-equipped delivery facility for women with near-term and term pre-eclampsia 4. Ensure magnesium sulphate availability to prevent severe pre-eclampsia and eclampsia-related maternal deaths, and 5. Identify specific barriers for implementation of these guidelines and correct them accordingly. Only by systematic implementations of these guidelines, we may have a chance to decrease the mortality of pre-eclampsia an its complications as a killer number one of mothers in developing countries.

Foreign Direct Investment in Pharmaceutical Sector: Role Analysis and Case Study

India’s economic reforms since 1990s and World Trade Organisation’s agreement on trade related aspect of Intellectual Property Rights have caused significant changes in the operational environment of Indian Pharmaceutical industry (IPI). This study examines the Foreign Direct Investment flows into the firm of IPI. Foreign companies dominates the Indian pharmacy industry due to availability of cheap labour. The basic opinion is that the Expenditure on Research &amp; development is very low in India. The General Agreement on Tariffs and Trade (GATT) and Trade Related Aspects of Intellectual Property Rights (TRIPS) has an adverse impact on pricing of pharmaceutical products. The Indian pharmaceutical industry has developed through a range of governmental incentives and, foreign firms that have invested in the industry have additionally contributed to the growth. The firms with foreign ownership experience higher productivity levels. It is possible that under the new patent laws, MNCs will start to outsource even patented drugs in India; consequently Researcher recommends that the government must look at the option of alternative public policies like public procurement of generic drugs. The domestic industry should be encouraged to produce cheap medicines. The R&amp;D from the foreign companies must be encouraged. Researcher’s limitation in this secondary research is that the quality of secondary research should be scrutinized closely since the origins of the information may be questionable.

Existing bitter medicines for fighting 2019-nCoV-associated infectious diseases.

The sudden outbreak of COVID‐19 has led to more than seven thousand deaths. Unfortunately, there are no specific drugs available to cure this disease. Type 2 taste receptors (TAS2Rs) may play an important role in host defense mechanisms. Based on the idea of host‐directed therapy (HDT), we performed a negative co‐expression analysis using big data of 60 000 Affymetrix expression arrays and 5000 TCGA data sets to determine the functions of TAS2R10, which can be activated by numerous bitter substances. Excitingly, we found that the main functions of TAS2R10 involved controlling infectious diseases caused by bacteria, viruses, and parasites, suggesting that TAS2R10 is a key trigger of host defense pathways. To quickly guide the clinical treatment of 2019‐nCoV, we searched currently available drugs that are agonists of TAS2Rs. We identified many cheap, available, and safe medicines, such as diphenidol, quinine, chloroquine, artemisinin, chlorpheniramine, yohimbine, and dextromethorphan, which may target the most common symptoms caused by 2019‐nCoV. We suggest that a cocktail‐like recipe of existing bitter drugs may help doctors to fight this catastrophic disease and that the general public may drink or eat bitter substances, such as coffee, tea, or bitter vegetables, to reduce the risk of infection.

Recent patents in anti-wart treatment.

Warts, small skin protuberances caused by human papillomavirus, are not life-threatening, but can be unsightly, embarrassing, uncomfortable and potentially contagious. They may regress naturally but over a prolonged time. Hence wart-afflicted people seek prescribed or over-the-counter therapies. Out of the innumerable marketable anti-wart medications, only a few are effective. Besides, frequent applications over months and certain undesirable side effects limit their success rates. Recurrences are also known. Hence the search for an effective, safe, cheap and quick medicine that is easy to apply continues. A number of patents for anti-wart therapies have been filed in the last few years. In this article, we enlist the recent anti-wart patents and find out those holding promise in the future.

Role of Demographic, Cognitive, Social Factors and Personality Trait on Treatment Modality Related Decision Making: A Conceptual Framework

Purpose: Understanding individual’s treatment modality related preference and choice-behavior is prerequisite for equitable distribution of community medicine and Health Human Resource planning. Standard models emphasize on demographic determinants and need-based perception, loosely incorporating social affecters, cognitive components and personality trait. This study addresses these factors separately and integrates into a statistically valid model. Methodology: Cross sectional study with sample size n=300 and 30 point questionnaire. Items are treated with exploratory factor analysis and regressed with preference and choice. Maximum likelihood estimates led to a path model. Results: 40.3% prefer CAM and 51.3% used it in last 12 months. Male, people with higher education, low disease burden and making decision in-group, choose CAM and believe Conventional Medicine has side effect, CAM cures all disease, cheaper and usage along-with Conventional Medicine, is better. Extraversion has positive (B=0.693,p<0.001), Conscientiousness (B=-.306,p<0.001) has negative effect on CAM usage. The integrated model shows 12 months usage score has strong negative prediction to stated CAM preference, whereas cognitive component is strongest predictor of CAM preference and conscientiousness acts negatively on choice and preference. Disease burden acts as need factor and social effect as external influence over CAM preference. Conclusion: Separately, demographic, cognitive, social factors, disease burden and personality traits influence treatment decision but the integrated path model shows factors act differently on preference and choice behaviour and also at different levels. This understanding will contribute to modify the existing conceptual models of healthcare utilization, facilitating the healthcare strategic planning and distribution system, related to health human resource management

Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV

Chikungunya fever is a major public health issue in India affecting millions of people and occurs due to Chikungunya. Chikungunya virus (CHIKV) is a single stranded RNA virus from the family of Togaviridae and genus alpha virus. It contain three structural proteins: glycosylated E1 and E2, embedded in the viral envelope, and a non-glycosylated nucleocapsid protein. Till date, researchers are working on inhibition of CHIKV but till now no cheap and effective medicine is available in the market. Therefore, the authors of this work thought of isoquinoline based noscapine to inhibit the nsP3 protease of CHIKV. The aim of the work is to understand the mechanism for the synthesis of noscapine theoretically using DFT. Further study the potential of all four isomers of noscapines {(13 (S,R), 14 (R,R), 15 (R,S) and 16 (S,S)} against nsP3 protease of CHIKV with the help of docking and MD simulation. The integrated e-pharmacophore binding affinity based virtual screening, docking and molecular dynamics simulation recognized four hits isomers as inhibition nsP3 protease of CHIKV. The docking energies of all the isomers of noscapine (13–16) with nsP3 protease CHIKV was found out to be more negative than baicalin (−8.06 kcal/mol) on selected sites. Amongst the isomers of noscapine, CMPD 13 possessed best binding affinity with four hydrogen bonding interactions. Further, ADME properties and blood-brain barrier permeability properties have been calculated. DFT studies of all the isomers of noscapine was investigated.

Promotion of Indian Drugs in Media

The Indian pharmaceutical industry is very wide and in volume it has been ranked 3rd in the world. It is contributing to 10% of the total pharmaceutical production. In terms of value the pharmaceutical industry is 14th largest in the world. As far as market is concerned it is 1.5% of the total pharmaceutical market. India is a good source of good quality and cheap medicines with strong retail base. It is also a hub for clinical trials, biotechnology, contract research, and clinical data management services. There has been tremendous competition among all pharmaceutical companies. In this competitive situation, media has emerged as a strong tool to promote pharmaceutical drug to end customers. This research paper contributes to the different aspects of pharmaceutical drug promotion in media in India.

Cross verification of prescribing trends through loop evaluation of physicians, patients and medical store personnel

BackgroundPrescription connects physician, patient and community pharmacy personnel who can help in understanding prescribing pattern. The present study was aimed to get an insight of viewpoints of all members involved in progression of events from prescription to drug purchase, i.e., physician, patient and medical-store personals regarding the prescription pattern in Pakistan.MethodsTherefore, a cross-sectional study was conducted in four provinces and capital territory (Islamabad) of Pakistan to evaluate the perception of physicians, patients and medical stores/pharmacy personnel of the prescribing trends in Pakistan.ResultsResponse rate was higher from Punjab and lower in Sindh. Responses of 981 walk-in patients with 393 physicians and 618 medical stores/pharmacies were received and statistically evaluated. The majority of physicians, patients and pharmacists/medical store personnel considered the medicines of multinational manufacturers as more effective. Physicians considered their prescribing cost-effective. However, majority of patients as well as pharmacists/medical store personnel strongly disagreed or disagreed with this notion that physicians prescribe cheap medicines. Furthermore, physicians and patients reported that medicines of local companies were not as effective as the medicines of multinational manufacturers, which were contrary to what pharmacists thought. Majority of physicians disagreed that their prescribing was under the influence of medical stores in their vicinity. The response of most of the patients (40.5%) was in line with that of physicians whereas 32% pharmacist/medical store personnel agreed. Nearly half of the physicians strongly agreed or agreed that patients demand medicines of multinational companies. Contrarily, a majority of patients and medical store personnel denied that patients demand for the medicines of multinational manufacturers.ConclusionThe study highlighted that there was a need to develop policy guidelines at the level of Federal Government and Drug Regulatory Authority of Pakistan in connection with prescribing practices to reduce the variation in perception of key stakholders involved in drug use process.

Między reklamą a nazwą własną. Przymiotnik tani w nazwach polskich aptek

Between an Advertisment and a Proper Name. The Adjective Tani ‘Cheap’ in the Names of Polish Pharmacies The paper considers a particular case of onomastic motivation, providing examples of the use of the adjective tani ‘cheap’ in the creation of pharmacy names in Poland (e.g. Tanie Leki ‘cheap medicines’, Tania Apteka ‘cheap pharmacy’). This Polish word is frequently used in marketing, both as an element of company names and marketing slogans. In many instances tani constitutes part of a complex pharmacy name, e.g.: Calotygodniowa Apteka Familijna — Tylko Tanie Leki, Super Tania Apteka im. Zawiszy Czarnego, Centrum Tanich Lekow — Apteka św. Barbary. On the basis of judgments from Polish administrative courts, the article discusses the question of the distinction or lack of one between advertisements and proper names. The significant fact is that the Pharmaceutical Law has prohibited the advertising of the operations of pharmacies since 2012 and, as a result, the use of names with the component tani was found to be in violation of the provision. In response to this, the owners of stores have argued that the proper name refers to the object alone, having no literal meaning. The controversial phrases were used to create legal names which are placed on signboards and in announcements. The paper focuses on a more general problem: chrematonyms and appellative lexis can hardly be distinguished due to their persuasive and marketing value.

The effect of eye exercise, triphala kwath eyewash, and instillation of distilled water on computer vision syndrome

Background: Computer vision syndrome (CVS) is a serious problem for the millions of people who spend hours in front of a computer. In modern lifestyle, every person is getting affected to the radiations caused by video display terminals, computer, television, and CFL lamp, mobile etc. The catastrophic effect of CVS has resulted in low performance and extreme discomfort to the sufferer. Being a disease of modern era,”it is difficult to get the nearest resembling disease in Ayurveda, but relief can be obtained by following Dinacharya, Rutucharya and basic principles of Ayurveda . So this study includes Eye exercise, Triphala kwath Eye Wash and distilled water eyewash. Aims & Objectives: The present study aimed to compare the efficacy of Eye exercise Triphala Kwath eyewash and instillation of distilled water in the management of CVS and To provide easily available, efficient, and cheaper medicine. Materials and Methods:The total sample size was 80. Each group consist of 40 sample size. Group I treated with eye exercise and Triphala Kwath eyewash and Group II treated with eye exercise and distilled water eyewash. Clinical Eye Examination done before treatment (D0), Follow up every 7th day upto 42 days .The effect of intervention was assure. Result:The results of the study revealed average 55% relief for group I for most of the subjective criteria and objective criteria. Conclusion:Eye exercise and Triphala Kwath eyewash is more significant than eye exercise and instillation of distilled water.

Swedish patients' trust in the bioequivalence of interchangeable generics. What factors are important for low trust?

Background:Generic substitution (GS), is a cost-containment strategy meant to contain pharmaceutical expenditure without compromising health objectives. In order to shape GS into a policy that is both efficient and safe it is crucial to understand which factors are most important for patients’ trust in GS.Objective:To assess Swedish patients’ level of trust in the bioequivalence of cheap and expensive generic medicines, and the association between trust and various factors.Methods:A cross-sectional study was conducted. Questionnaires were handed out at 12 community pharmacies in Sweden, selected through stratified sampling, between March and April 2015. The questionnaire included seven socio-demographic questions in addition to 18 items divided into three sections: the ‘views on generic medicine’-scale, information on and prior experiences of GS, financial aspects and change of color/name. Odds Ratios (ORs) were estimated applying adjusted logistic regression analyses with trust in the bioequivalence of generic medicines used as outcome variable and various factors as predictors.Results:A total of 719 patients participated (response rate 85.7%). The results show that 70.7% of the respondents’ trust that cheap and expensive interchangeable generic medicines are equal. Of the respondents 36.0% considered the change in appearance and 40.8% the change in names to complicate adherence. Lower trust in the bioequivalence of generic medicines were associated with being female (aOR=1.82, 95%CI 1.20:2.75, p<0.01), patients perceiving that changes in product name and appearance make adherence more complicated (aOR=2.18, 95%CI 1.48:3.19, p<0.001), disagreeing in that GS saves money for me (the customer) (aOR=2.68, 95%CI 1.58:4.55, p<0.001) or that GS saves money for society (aOR=3.21, 95%CI 1.46:7.08, p<0.01).Conclusions:Seven out of ten respondents had trust in the bioequivalence of generic medicines, and one in three considered GS to complicate adherence. Four factors were associated with lower trust in GS, i.e. female gender, agreeing that changes in product name and appearance complicates adherence, disagreeing in that GS saves money for me or disagreeing in that GS saves money for the society. Low trust in GS needs to be addressed, not least in the communication between health professionals and patients.

The current status and effects of emergency drug shortages in China: Perceptions of emergency department physicians.

ObjectivesThe shortage of emergency drugs in China is severe. This study aimed to characterize emergency drug shortages in China and to measure their effects.MethodsAn online questionnaire based on a literature review was sent to emergency department physicians in Chinese secondary and tertiary hospitals from November 2016 to February 2017. The survey asked physicians questions about their experiences with emergency drug shortages.ResultsIn total, 236 physicians from 29 provinces participated in the survey. According to their responses, 90.7% of the respondents experienced drug shortages during the last year. More than half of the physicians (65.7%) reported that drug shortages occurred at least once a month. Hospitals in the eastern and western regions of China had more emergency drugs in shortage than hospitals in central China, especially those with many inpatient beds (≥800). In addition, the shortage situation was more serious in secondary hospitals than in tertiary hospitals. More respondents agreed that original medicines, injections, essential medicines, medicines without alternative agents and cheap medicines were more susceptible to shortages than generics, oral medicines, nonessential medicines, medicines with alternative agents and expensive medicines, respectively. Most respondents thought that drug shortages always, often or sometimes affected patients [delayed therapy (62.6%), longer rescue and recovery times (58.9%) and higher costs (58.7%)] and physicians [inconvenience (81.0%), higher pressure (76.5%) and harm to patient-doctor relationships (72%)] and compromised hospital reputations (55.1%).ConclusionsThe shortage of emergency drugs in China is serious, especially in secondary hospitals located in eastern and western China. Emergency drug shortages have significant effects on patients and physicians.

Views and perceptions about locally manufactured medicines in Ethiopia: a qualitative study of physicians, patients and regulatory authorities

BackgroundBecause of their cost, the use of locally produced, bioequivalent, generic drugs is universally recommended. In Ethiopia. while the government is committed to raising the market share and use of locally produced drugs, the process is hampered by the lack of a bioequivalence testing centre to strengthen the regulatory environment and deliver quality-assured local medicines. The purpose of this study is to assess the views and perceptions of key regulatory stakeholders, physicians and patients about locally produced generic medicines.MethodsA descriptive qualitative study, using focus group discussions and key informant interviews, was conducted. Five key informant interviews (two senior regulatory authority members and 3 institutional review board members) as well as 4 focus group discussions (2 with physicians and 2 with patients) were held. Data were analysed using an inductive, thematic process.ResultsFour major themes emerged: awareness of lack of bioequivalence profiles associated with local medicines, perceptions about the quality and effectiveness of local medicines, quality and efficacy of imported medicines from developing countries and quality and efficacy of cheaper medicines. All institutional review board members were aware of bioequivalence issues. However, many physicians lacked detailed knowledge about bioequivalence, its clinical relevance and the lack of bioequivalence data for local medicines. All institutional review board members, physicians and male patients, but not female patients, were concerned about the quality and effectiveness of local medicines. Female patients were more confident about the locally produced drugs. In addition, some physicians and patients were not confident about the quality and effectiveness of cheaper drugs and drugs imported from developing countries. Government officials believed that local drugs are reliable.ConclusionThe success of promoting the use of inexpensive local medicines and changing the perception of the community depends not only on increasing the domestic market share held by local companies, but also on the capacity of the regulatory environment and companies to produce quality assured medicines and to overcome misconceptions. Among other initiatives, establishing an accredited bioequivalence centre in the country needs to be addressed urgently.