World Health Organization Model List Research Articles

PRESCRIPTION PATTERN ANALYSIS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN TERTIARY CARE HOSPITAL

Objective: The aim of the study was to analyze the prescription pattern of non-steroidal anti-inflammatory drugs (NSAIDs) and to identify the commonly used NSAIDs and their drug-related problems (DRPs). Methods: A prospective and cross-sectional study on prescription pattern analysis of NSAIDs was conducted for the period of 6 months. Results: Prescriptions of 150 patients containing at least one NSAIDs were analyzed. About 56% of the prescription were prescribed for males and 44% prescription were female. NSAIDs were more prescribed for below 60-year age group (47%) but were most frequently used by 61–70-year age group (21%). Subjects were regularly prescribed with acetaminophen (95%) and diclofenac (22%). Among all the prescriptions, (19%) of the prescriptions contained NSAIDs in the form of fixed dose combinations (FDCs). About 37% of prescriptions had other analgesic coprescribed along with NSAIDs amid which tramadol was in majority (22%). Prescription was also coprescribed with antibiotic (90%) and gastroprotective agents (GPAs) (97%) that consisted of pantoprazole belonging to the class of proton pump inhibitors which was the persistently prescribed GPA (86%). Due to coprescription, (3%) suspected drug-drug interactions (DDIs) were observed. Conclusion: The goal of studying prescribing patterns was to monitor, assess, and, if required, advise changes in medical practitioners’ prescribing behavior to offer quality medical treatment and reasonable drug use. The prescribing pattern was rational and in accordance with national list of essential medicine (NLEM-2015) but was not in accordance with the World Health Organization (WHO) model list of essential medicines.

Comparison of the 22nd World Health Organization Model List of Essential Medicines with the explicit criteria for the treatment of chronicity in elderly patients

ObjectivesThis study analysed whether the Model List of Essential Medicines is suitable for elderly patients. Furthermore, it investigated the specific issues that should be considered when prescribing a drug and...

National adaptation and implementation of WHO Model List of Essential Medicines: A qualitative evidence synthesis.

The World Health Organization Model List of Essential Medicines (WHO EML) has played a critical role in guiding the country-level selection and financing of medicines for more than 4 decades. It continues to be a relevant evidence-based policy that can support universal health coverage (UHC) and access to essential medicines. The objective of this review was to identify factors affecting adaptation and implementation of WHO EML at the national level. We conducted a qualitative evidence synthesis by searching 10 databases (including CINAHL, Embase, Ovid MEDLINE, Scopus, and Web of Science) through October 2021. Primary qualitative studies focused on country-level implementation of WHO EML were included. The qualitative findings were populated in the Supporting the Use of Research Evidence (SURE) framework, and key themes were identified through an iterative process. We appraised the papers using the Critical Appraisal Skills Programme (CASP) tool and assessed our confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation working group-Confidence in Evidence from Reviews of Qualitative research (GRADE-CERQual). We screened 1,567 unique citations, reviewed 183 full texts, and included 23 studies, from 30 settings. Non-English studies and experiences and perceptions of stakeholders published in gray literature were not collected. Our findings centered around 3 main ideas pertaining to national adaptation and implementation of WHO EML: (1) the importance of designing institutions, governance, and leadership for national medicines lists (NMLs), particularly the consideration of transparency, coordination capacity, legislative mechanisms, managing regional differences, and clinical guidance; (2) the capacity to manage evidence to inform NML updates, including processes for contextualizing global evidence, utilizing local data and expert knowledge, and assessing budget impact, to which locally relevant cost-effectiveness information plays an important role; and (3) the influence of NML on purchasing and prescribing by altering provider incentives, through linkages to systems for financing and procurement and donor influence. This qualitative evidence synthesis underscores the complexity and interdependencies inherent to implementation of WHO EML. To maximize the value of NMLs, greater investments should be made in processes and institutions that are needed to support various stages of the implementation pathway from global norms to adjusting prescribed behavior. Moreover, further research on linkages between NMLs, procurement, and the availability of medicines will provide additional insight into optimal NML implementation. PROSPERO CRD42018104112.

Evaluation of rationality of fixed dose combinations of antimicrobials available in Indian market

Background: The antimicrobial resistance is alarming at present. One of the important factors for resistance is use of irrational fixed dose combinations. Thus, objective was to critically analyze the rationality of FDCs of antimicrobial agents currently available in India.Methods: The FDCs of AMAs enlisted in Indian Drug Review 2019 were analyzed by 8 point criteria tool. Analysis includes number of active pharmacological ingredients, approval by central drug standard control organization, listing in world health organization model list of essential medicines (2019) or Government of India national list of essential medicines (2015). Literature search was used for assessing efficacy, safety, pharmacokinetic and pharmacodynamic interactions and advantages of each FDC. Each criterion was assigned score one, if positive and minus one, if negative leading to total score of 12. FDC with score of ≥7 was considered as rational. Results: The FDCs of AMA available in Indian market were 116 while FDCs included in WHO model list, 2019 were 24. Majority of FDCs available were irrational that include combination of antibacterial with bromhexine, carbocisteine, ambroxol, serratiopeptidase, antiamoebic and antifungal etc. Most of the rational FDCs belong to antiretroviral, antitubercular and antimalarial drugs. Conclusions: Most of the FDCs of AMAs available in Indian market are irrational. These needs educating the prescribers including resident doctors. There is need to critically review such FDCs by drug regulators with strict action regarding manufacturing and marketing.

Addition of direct oral anticoagulants to the World Health Organization model list of essential medicines for the treatment of atrial fibrillation: An African perspective.

Atrial fibrillation (AF) is a major cause of adverse cardiovascular outcomes, and its prevalence is fast rising in Africa. The advent of direct oral anticoagulants (DOACs) has been a major revolution for the prevention of AF-related stroke and systemic embolism given the significant advantage over vitamin K antagonists in terms of both efficacy, safety, and adherence. However, due to their high cost, equitable access to DOACs has been a challenge, especially in low- and middle-income countries. Therefore, the recent addition of DOACs to the 21st WHO list of essential medicines comes as good news. African governments should take this opportunity to scale up the accessibility to DOACs for African patients with AF. This could be achieved through advocacy, appropriate training of health professionals, task shifting, patient education, strategic partnership to increase availability and quality of low-cost generic drugs, and appropriate medico-economic studies.

Disparities in Access to Systemic Treatment for Breast Cancer in Thailand and Major Asian Territories.

PurposeBreast cancer (BC) treatment has shifted from chemotherapy to targeted therapy. Several targeted agents have demonstrated an improvement in survival. Given that national healthcare resources were correlated with the cancer mortality-to-incidence ratio, we compared access to BC drugs in Thailand with that in other Asian countries.MethodsBC experts involved in the Breast International Group (BIG)-Asia in six representative groups for countries or special administrative region (SAR) in Asia (Hong Kong SAR, Japan, Korea, Taiwan, Thailand, and Singapore) were invited to participate in the survey. The questionnaire addressed national health reimbursement schemes, molecular testing for early BC (EBC), availability and accessibility of BC drugs. Accessibility and reimbursement of the drugs were reported based on their listing as essential medicines in the World Health Organization Model List of Essential Medicines (WHO-EML) and their nomination as effective drugs in the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). The study was approved by all participating BIG-Asia organizations in November 2021.ResultsGenomic tests for EBC were non-reimbursable in all surveyed territories. Reimbursement and co-payment of BC drugs vary between and within these regions (particularly Thailand). Most drugs in the WHO-EML and ESMO-MCBS (A/B for EBC and 4/5 for advanced BC) were accessible in all surveyed territories. However, the accessibility of effective but costly WHO-EML and ESMO-MCBS drugs was not uniform in Thailand. There was an evident disparity for individuals covered by the Thai Social Security/Universal Health Coverage schemes.ConclusionEssential BC drugs are generally accessible in selected BIG-Asia countries or SAR. There is a disparity in accessing high-cost drugs in Thailand compared with other Asian territories.

Mutual Prodrugs of 5-Fluorouracil: From a Classic Chemotherapeutic Agent to Novel Potential Anticancer Drugs.

The development of potent antitumor agents with a low toxicological profile against healthy cells is still one of the greatest challenges facing medicinal chemistry. In this context, the “mutual prodrug” approach has emerged as a potential tool to overcome undesirable physicochemical features and mitigate the side effects of approved drugs. Among broad‐spectrum chemotherapeutics available for clinical use today, 5‐fluorouracil (5‐FU) is one of the most representative, also included in the World Health Organization model list of essential medicines. Unfortunately, severe side effects and drug resistance phenomena are still the primary limits and drawbacks in its clinical use. This review describes the progress made over the last ten years in developing 5‐FU‐based mutual prodrugs to improve the therapeutic profile and achieve targeted delivery to cancer tissues.

Improving the Russian-language Wikipedia articles on medicines using new knowledge Cochrane

Aim. To evaluate the effectiveness of the Cochrane Russia Initiative to improve the articles of the Russian-language Wikipedia by including information from Cochrane Systematic Reviews (CSR) to ensure the accuracy and impartiality of their content as an information basis for the quality use of medicines by doctors and the public.
 Methods. Wikipedia articles on selected drugs were improved by introducing evidence from Cochrane Systematic Reviews Cochrenized. A parallel open-label non-randomized controlled intervention study was conducted. We assigned 2 groups of drugs and Wikipedia articles about them: the intervention group (Cochrenization) and the control group (36 articles each). Control group articles were not edited. The change in the number of visits to Wikipedia pages for the year (20182019) was measured, the statistical significance of the differences was assessed by using the Wilcoxon signed-rank test.
 Results. We edited 36 Wikipedia articles, including 13 articles on migraine treatment, 9 diabetes mellitus, 14 pain and inflammation articles. These articles constituted the intervention group. The control group consisted of articles on cardiovascular (11), gastrointestinal (14) and dermatological agents (11). We used the Cochrane Russia Initiative dashboard on Wikipedia to compare the number of article views before and after the intervention and Cochrane analytics on demand for translations of Cochrane systematic reviews summaries. After Cochrenization, the number of Wikipedia article views (20182019) increased in total/average article views for treatments: migraines by 18%/47%, pain and inflammation 16%/43%, diabetes mellitus 18%/0%. Analysis of Cochrane reports showed an increase in the number of views of Cochrane systematic reviews summaries on the Cochrane.org website in general by 9 times and from Russian-speaking browsers by 11 times. Improvement of medicine-related articles of the Russian-language Wikipedia by the introduction of information from Cochrane systematic reviews was accompanied by an increase in their demand in terms of the number of views in general by 34%, with a similar increase in control (without intervention) (p-value of the experimental group 0.002, control 0.000). The Wikipedia articles on medicines, which belonged to the Russian Vital and Essential Drugs List or the World Health Organization Model List of Essential Medicines, got more views.
 Conclusion. The role of confounding factors justifies the feasibility of developing a methodology for studying the usefulness of improving Wikipedia articles, different from controlled trial research methodology; further inclusion of Cochrane knowledge into Wikipedia is needed.

Trends and patterns of antibiotic prescribing at orthopedic inpatient departments of two private-sector hospitals in Central India: A 10-year observational study.

Frequent antibiotic prescribing in departments with high infection risk like orthopedics prominently contributes to the global increase of antibiotic resistance. However, few studies present antibiotic prescribing patterns and trends among orthopedic inpatients. To compare and present the patterns and trends of antibiotic prescription over 10 years for orthopedic inpatients in a teaching (TH) and a non-teaching hospital (NTH) in Central India. Data from orthopedic inpatients (TH-6446; NTH-4397) were collected using a prospective cross-sectional study design. Patterns were compared based on the indications and corresponding antibiotic treatments, mean Defined Daily Doses (DDD)/1000 patient-days, adherence to the National List of Essential Medicines India (NLEMI) and the World Health Organization Model List of Essential Medicines (WHOMLEM). Antibiotic prescriptions were analyzed separately for the operated and the non-operated inpatients. Linear regression was used to analyze the time trends of antibiotic prescribing; in total through DDD/1000 patient-days and by antibiotic groups. Third generation cephalosporins were the most prescribed antibiotic class (TH-39%; NTH-65%) and fractures were the most common indications (TH-48%; NTH-48%). Majority of the operated inpatients (TH-99%; NTH-97%) were prescribed pre-operative prophylactic antibiotics. The non-operated inpatients were also prescribed antibiotics (TH-40%; NTH-75%), although few of them had infectious diagnoses (TH-8%; NTH-14%). Adherence to the NLEMI was lower (TH-31%; NTH-34%) than adherence to the WHOMLEM (TH-65%; NTH-62%) in both hospitals. Mean DDD/1000 patient-days was 16 times higher in the TH (2658) compared to the NTH (162). Total antibiotic prescribing increased over 10 years (TH-β = 3.23; NTH-β = 1.02). Substantial number of inpatients were prescribed antibiotics without clear infectious indications. Adherence to the NLEMI and the WHOMLEM was low in both hospitals. Antibiotic use increased in both hospitals over 10 years and was higher in the TH than in the NTH. The need for developing and implementing local antibiotic prescribing guidelines is emphasized.

Evaluation of Critical Quality Attributes of Immediate Release Ciprofloxacin Tablets of Different Pharmaceutical Companies in Bangladesh

Critical Quality Attributes (CQAs) is an important factor in Pharmaceutical development as it determines the strength, release of the API from SDFs, and stability of a pharmaceutical dosage form. Moreover, substandard and counterfeit drugs have been a major concern in recent days.Ciprofloxacin is a second-generation fluoroquinolone derivative that exerts its effects by inhibiting bacterial DNA gyrase (Topoisomerase II). It is used for the treatment of bacterial gastroenteritis, respiratory tract infections, controlling bronchitis and pneumonia caused by Gram negative bacteria. Ciprofloxacin has been listed in the World Health Organization (WHO) Model list of Essential Medicines. In recent decades, the pharmaceutical industry has been experiencing excellent growth in both local and international market.In our present study, we have analyzed theCritical Quality Attributes (CQAs) including length, thickness, friability, weight variation, hardness test and disintegration time of Ciprofloxacin tablet to study whether the ciprofloxacin immediate release tablets of different pharmaceutical companies available in the Bangladeshi market to assess whether they are compliant to BP or USP guidelines in respect of physical parameters. We have also performed statistical analysis and found that that all the tablets from different brands are within the BP or USP requirements. So, from the study, we reached the conclusion that the critical quality attributes for ciprofloxacin immediate release tablets of different pharmaceutical companies in Bangladesh ensure the appropriateness of their strength, purity, release of the API from SDFs, and stability.

Dual Effect of Prussian Blue Nanoparticles on Aβ40 Aggregation: β-Sheet Fibril Reduction and Copper Dyshomeostasis Regulation.

Alzheimer's disease (AD), affecting almost 50 million individuals worldwide, is currently the first cause of dementia. Despite the tremendous research efforts in the last decade, only four supportive or palliative drugs, namely, acetylcholinesterase (AChE) inhibitors donepezil, galantamine, and rivastigmine and the glutamate NMDA receptor antagonist memantine, are currently available. New therapeutic strategies are becoming prominent, such as the direct inhibition of amyloid formation or the regulation of metal homeostasis. In the present report, the potential use of Prussian blue (PB), a drug that is in the World Health Organization Model List of Essential Medicines, in AD treatment is demonstrated. Both in vitro and in cellulo studies indeed suggest that PB nanoparticles (PBNPs) are capable of reducing the formation of typical amyloid-β fibers (detected by thioflavin T fluorescence) and restoring the usual amyloid fibrillation pathway via chelation/sequestration of copper, which is found in high concentrations in senile plaques.

Drug utilization study in post-operative cases of obstetrics and gynecology department in a tertiary care hospital

Background: After any surgery, drugs are prescribed for analgesia, prevention of infection, nausea, vomiting, and to maintain the hemodynamic status. Drug utilization studies identify the associated problems and aid prescribers to optimize resource allocation and utilization. Aim and Objectives: This study was done to explore the utilization pattern of medications in obstetrics and gynecology post-operative cases for assessment of the following: (1) Various medications prescribed, (2) their route of administration, (3) duration of usage, and (4) the World Health Organization (WHO) core drug indicators. Materials and Methods: A retrospective observational case-sheet based study was conducted after obtaining approval from the Institutional Ethics Committee. Data were collected from case sheets dated May 1, 2018, to October 31, 2018, in the obstetrics and gynecology department using a structured pro format. Results: A total of 240 patients (247 encounters) were prescribed antimicrobials, analgesics, antacids, and intravenous (IV) fluids with an average of 7.25 drugs per encounter. Injectable drug was prescribed to 222 (89.88%) patients. Antimicrobials were prescribed to 168 patients (68.01%); most common being metronidazole which was prescribed to 120 patients (48.58%). Diclofenac was prescribed to 232 patients (93.93%) and Ranitidine to 239 patients (96.76%); these were the most commonly prescribed analgesic and antacid, respectively. Out of 68 different types of drugs prescribed, 16 (23.53%) were prescribed by their generic name and 51 (75%) were from the Essential Medicines WHO Model List (EML) (2015). Conclusions: Antimicrobials were moderately used in management of post-operative cases. Although only about a quarter of medications were prescribed by generic name, nearly three-fourths were from EML.

Is there a case for inclusion of medicines used to manage alcohol use disorder in the World Health Organization Model List of Essential Medicines?

Is there a case for inclusion of medicines used to manage alcohol use disorder in the World Health Organization Model List of Essential Medicines?

Access to essential anticancer medicines for children and adolescents in Europe

Essential anticancer medicines are an indispensable component of multidisciplinary treatment of paediatric malignancies. A European Society for Medical Oncology (ESMO) study reported inequalities in the availability of anticancer medicines for adult solid tumours and provided a model for the present survey. The aim of this survey was to assess the accessibility of essential medicines used in paediatric cancer patients aged 0 to 18 years across Europe from 2016 to2018. A list of medicines was drawn with input from the European Society for Paediatric Oncology (SIOP Europe) Clinical Research Council referring to the World Health Organization Model List of Essential Medicines for Children (WHO EMLc) 2017. A survey was sent to nominated national clinician and pharmacist rapporteurs and parent associations in up to 37 countries; answers were obtained from 34 countries. The full survey list contained 68 medicines, including 24 on the WHO EMLc 2017. Health professionals reported that 35% of all medicines were prescribed off-label in at least one country and that 44% were always available in >90% of countries. Only 63% of the EMLc 2017 medicines were reported as always available. The main determinant of unavailability was shortages, reported for 72% of medicines in at least one country. Out-of-pocket costs were reported in eight countries. Twenty-seven percent of orally administered medicines were never available in child-friendly formulations. Parents detailed individual efforts and challenges of facilitating ingestion of oral medicines as prescribed. Inequalities in access to pain control during procedures were reported by parents across Europe. Children and adolescents with cancer in Europe experience lack of access to essential medicines. Urgent actions are needed to address shortages, financial accessibility, availability of safe age-appropriate oral formulations, and pain management across Europe.

Antibiotic procurement and ABC analysis for a comprehensive primary health care clinic in the Eastern Cape province, South Africa.

BackgroundAntimicrobial resistance (AMR), a major threat to global public health, can be addressed using a managed care approach. This includes timely analysis of antibiotic consumption and procurement data to drive evidence-based policies and practices in healthcare facilities. ‘ABC analysis’ presents an opportunity for this.MethodsABC analysis data for a comprehensive Primary Health Care (PHC) clinic in the Eastern Cape province of South Africa was obtained from the Provincial Department of Health for 01 April 2015 to 31 March 2018. Procured antibiotics were analysed on the quantities purchased, total cost, route of administration and spectrum of activity. Antibiotic categorization was also carried out according to the World Health Organization Model List of Essential Medicines (WHO EML) 2017.ResultsAntibiotics made up approximately 7% of the total annual pharmaceutical expenditure. A total of 31, 35 and 34 antibiotics were procured in the first, second and third years, respectively. The most procured antibiotics were: (1) isoniazid, (2) flucloxacillin, (3) azithromycin, (4) a combination of rifampicin, isoniazid, pyrazinamide, and ethambutol and (5) amoxicillin. Overall, 55%, 2% and 15% of antibiotics accounted for the ‘Access’, ‘Watch’ and ‘Access and Watch’ categories, respectively, of the WHO EML. No ‘Reserve’ antibiotics were procured. The remaining 28% were antituberculosis medicines. Altogether, 89%, 8% and 3% of the antibiotics were respectively administered orally, systemically, and topically. A total of 58% were broad-spectrum and 42% were narrow-spectrum antibiotics.ConclusionOral antibiotics in the ‘Access’ category presented favourable usage of antibiotics. Decreasing the use of broad-spectrum antibiotics requires consideration.

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

SummaryCombinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model.

Preventive Effect of Muscone against Cisplatin Nephrotoxicity in LLC-PK1 Cells.

Cisplatin, one of the most common antitumor agents, is widely applied to treat various cancerous diseases and is included in the World Health Organization Model List of Essential Medicines. Cisplatin therapy is used to treat 10–20% of all cancerous cases, and its cure rate is especially high in testicular cancer (over 90%). However, a major side effect of this anticancer drug is nephrotoxicity, limiting treatment effect and reducing the quality of life in cancer patients. Muscone, an odoriferous constituent of musk, was confirmed to inhibit cisplatin-induced LLC-PK1 kidney proximal tubule cell death in a dose-dependent manner. In term of renal protective mechanism, muscone inhibited cisplatin oxidative toxicity by decreasing reactive oxygen species (ROS) level and stimulating HO-1 expression. Muscone also exerted anti-inflammation effect through inhibition of p38 phosphorylation. Furthermore, muscone mitigated cisplatin-induced apoptosis in LLC-PK1 cells via both intrinsic and extrinsic pathways by inhibiting pro-apoptotic protein Bax expression, and cleaved caspase-3, 7, and 8; and increase of anti-apoptotic protein Bcl-2 level. In addition, the anti-apoptotic effect of muscone also was enhanced by preventing p53 expression and its phosphorylation. Our study showed that muscone may be a potential protective agent against cisplatin-induced nephrotoxicity.

Do South Asian women with menopausal symptoms have access to optimal therapy?

Background Menopausal symptoms can have a significant impact on a woman's quality of life. Information on availability of menopausal hormone therapy (MHT) in National Essential Medicines Lists (NEMLs) of South Asian (SA) countries has not been widely studied. Objective To review the availability of non-injectable MHT included in NEMLs of SA countries and to assess differences in availability compared to the recommended MHT preparations in the World Health Organization (WHO) model essential medicines list and the list of MHT available to women of a developed country in the Asia Pacific Region, while comparing with the healthcare expenditure and country's economic status. Methods Most recent NEMLs were obtained from all eight SA counties by visiting the Ministry of health/regulatory website of the respective country. Latest WHO model essential medicines list and Pharmaceuticals Benefits Scheme (PBS) schedule from Australia were obtained from the WHO and PBS websites respectively. Per capita health expenditure was obtained from The WHO Global Health Expenditure Database. Two investigators extracted the non-injectable MHT preparations independently from NEMLs and conducted the comparison. Results Except in two countries, in all other SA coun­tries NEMLs were updated within the preceding five years. According to available data, seven SA countries had at least one separate preparation of oestrogen suitable for MHT while all countries had a separate progesterone preparation suitable for MHT. The oestrogen preparations available in the SA NEMLs were limited to either ethinyl estradiol or conjugated oestrogen tablets whilst in the WHO model, oestrogen preparations were not specified. In Australia, estradiol tablets were the only available oral oestrogen while there were four more different dosage forms of oestrogens available through the PBS Scheme. Progesterone preparations found in SA countries, WHO list and PBS schedule were similar, but oestrogen progesterone combination MHT preparations were only available in the PBS schedule. Per capita health expenditure was much higher in Australia compared to SA countries where a wide variation was observed. Conclusions The available evidence suggests that a larger population of SA women have access only to a very limited number of options if in need of MHT. In contrast, importance of MHT is highlighted in PBS Schedule. Although per capita health expenditure was low in SA countries, given that MHT products are relatively low cost and that there is a large proportion of women in menopausal age in this region, it would be imperative to update the WHO model list and NEMLs of SA countries to address the growing need of safe MHT and to improve the quality of life of postlnenopausal women in our region.

The "Square Box": Therapeutic Equivalence as a Foundation of the WHO Model List of Essential Medicines.

Every two years, the World Health Organization (WHO) updates its Model List of Essential Medicines, intended as a guide for countries to adopt or adapt in accordance with local priorities and treatment guidelines, for the development of national essential medicines lists. When more than one therapeutic option is available for a given indication, the WHO Model List often includes a single medicine as representative of a group of equivalent and interchangeable medicines. The representative medicine of that group is listed with an accompanying ‘square box’ symbol. The intended purpose of the square box is to highlight pharmacological classes or groups of medicines for which countries, institutions and health professionals can assume homogeneous therapeutic efficacy and safety and select the most appropriate single medicine based on price, local availability, and acceptability. Though this concept of therapeutic equivalence within a therapeutic class has been endorsed by most authoritative textbooks of pharmacology since Goodman & Gilman’s The Pharmacological Basis of Therapeutics and evidence-based guidelines, marketing forces have often made claims on individual drugs to distinguish them beyond relevant differences shown by reliable evidence: this has generated the concept of “me-too drugs” with its double meaning—i.e., market latecomers differing minimally from products preceding them and whose marketing budgets have significant opportunity costs, or medicines which may be useful to substitute for equivalent products in the event of shortages. The square box concept is applied in the context of a comprehensive list: therapeutic equivalence or interchangeability cannot always be easily established. Different interpretations have been applied to different groups of medicines over the 40+ year history of the Model List. This paper presents the concept of the square box, provides key examples and guidance on how square box listings should be practically interpreted in the development and implementation of national essential medicine lists, considers the applicability of a square box listing concept to biologic medicines and proposes that an updated review of the square box concept and listings is warranted.

Inclusion in the World Health Organization Model List of Essential Medicines of Non-Vitamin K Anticoagulants for Treatment of Non-Valvular Atrial Fibrillation: A Step Towards Reducing the Burden of Cardiovascular Morbidity and Mortality.

Non-vitamin K antagonist oral anticoagulants (NOACs) represent a paradigm shift in the treatment of non-valvular atrial fibrillation (AF) with major practice guidelines around the world recommending NOACs over vitamin K antagonist oral anticoagulants for initial treatment of AF for stroke prevention. Here we describe the evidence collated and the process followed for the successful inclusion of NOACs into the 21st WHO Model List of Essential Medicines (EML).Individual NOACs have been reported to be non-inferior or superior to warfarin in preventing stroke and systemic embolism in eligible AF patients with a reduction in the risk of stroke and systemic embolism and a lower risk of major bleeding in patients with non-valvular AF compared with warfarin in both RCTs and real-world data.The successful inclusion of NOACs in the WHO EML is an important step forward in the global fight against cardiovascular morbidity and mortality, especially in low- and middle-income countries, where the burden of disease is high and limited access to diagnosis and treatment translates into a higher burden of morbidity, mortality, and economic costs.