Global, regional and national availability of essential medicines for children, 2009-2020: a systematic review and meta-analysis.

BACKGROUND: Access to essential medicines is a vital component of universal health coverage. The low availability of essential medicines for children (EMC) has led the World Health Organization (WHO) to issue a number of resolutions calling on member states on its improvement. But its global progress has been unclear. We aimed to systematically evaluate the progress of availability of EMC over the past decade across economic regions and countries. METHODS: We searched eight databases from inception to December 2021 and reference lists to identify included studies. Two reviewers independently conducted literature screening, data extraction and quality evaluation. This study was registered with PROSPERO, CRD42022314003. RESULTS: Overall, 22 cross-sectional studies covering 17 countries, 4 income groups were included. Globally, the average availability rates of EMC were 39.0% (95%CI: 35.5-42.5%) in 2009-2015 and 43.1% (95%CI: 40.1-46.2%) in 2016-2020. Based on the World Bank classification of economic regions, income was not proportional to availability. Nationally, the availability rate of EMC was reasonable and high (> 50%) in only 4 countries, and low or very low for the rest 13 countries. The availability rates of EMC in primary healthcare centers had increased, while that for other levels of hospitals slightly declined. The availability of original medicines decreased while that of generic medicines was stable. All drug categories had not achieved the high availability rate. CONCLUSION: The availability rate of EMC was low globally, with slight increase in the last decade. Continuous monitoring and timely reporting of the availability of EMC are also needed to facilitate targets setting and inform relevant policy making.

Availability of essential medicines, progress and regional distribution in China: a systematic review and meta-analysis.

Background: Essential medicines are the backbone of healthcare and meet the priority healthcare needs of the population. However, approximately one-third of the global population does not have access to essential medicines. Although China formulated essential medicine policies in 2009, the progress of availability of essential medicines and regional variations remains unknown. Therefore, this study was conducted to evaluate the availability of essential medicines, their progress, and regional distribution in China in the last decade. Methods: We searched eight databases from their inception to February 2022, relevant websites, and reference lists of included studies. Two reviewers selected studies, extracted data, and evaluated the risk of bias independently. Meta-analyses were performed to quantify the availability of essential medicines, their progress, and regional distribution. Results: Overall 36 cross-sectional studies conducted from 2009 to 2019 were included, with regional data for 14 provinces. The availability of essential medicines in 2015-2019 [28.1%, 95% confidence interval (CI): 26.4-29.9%] was similar to that in 2009-2014 (29.4%, 95% CI: 27.5-31.3%); lower in the Western region (19.8%, 95% CI: 18.1-21.5%) than Eastern (33.8%, 95% CI: 31.6-36.1%) and Central region (34.5%, 95% CI: 30.6-38.5%); very low for 8 Anatomical Therapeutic Chemical (ATC) categories (57.1%), and low for 5 categories (35.7%) among all ATC groups. Conclusion: The availability of essential medicines in China is low compared with the World Health Organization goal, has not changed much in the last decade, is unequal across regions, and lacks data for half of provinces. For policy-making, the monitoring system of the availability of essential medicines is to be strengthened to enable long-term surveillance, especially in provinces where the data has been missing. Meanwhile, Joint efforts from all stakeholders are warranted to improve the availability of essential medicines in China toward the universal health coverage target. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=315267, identifier: PROSPERO CRD42022315267.

The price and affordability of essential medicines, progress and regional distribution in China: a systematic review.

Background: Essential medicine is a vital component to assure universal access to quality healthcare. However, the trend of affordability to essential medicines in China and its regional differences were not yet fully understood. This study aimed to systematically evaluate the price and affordability of essential medicines, their progress, and regional distribution in China in the last decades. Methods: We searched seven databases and three websites for potentially eligible studies from inception until March 2022. Studies on the price and affordability of essential medicines investigated in China were included. Median and interquartile range (IQR) was used to describe the price and affordability of essential medicines, and compared in three periods, before 2009, from 2009 to 2014, and from 2015 to 2019. Subgroup analysis was performed to examine the price and affordability by regions, health facilities, and ATC categories of medicines. The study was registered with PROSPERO (CRD42022310173). Results: A total of 65 studies including 11,639 health facilities investigated between 2006 and 2019 were included in this review. Median price ratios (MPR) and affordability of essential medicines were reported in 44 studies and 50 studies, respectively. The median MPRs of essential medicines in China was 1.59 (IQR: 5.39), with a tendency to rise first and then fall from 2006 to 2019. And the median affordability was equal to 0.88 (IQR: 2.58) days' wage of the lowest paid unskilled government worker, but steadily rose from 2006 to 2019. Subgroup analysis showed that the affordability in the western region (1.40, IQR: 2.88), urban area (0.95, IQR: 2.80), private sector (0.90, IQR: 2.30), of originator brands (OB) (2.90, IQR: 6.68), and antineoplastic and immunomodulating agents (5.68, IQR: 56.47) were worse than their counterparts. Conclusion: The prices of essential medicine were higher than international level, the overall affordability of essential medicines in China is acceptable but poor in the western region, for OB drugs and anti-cancer medicines. Further national essential medicine policies are needed to reduce regional disparities and improve the affordability of expensive drugs. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

Lessons from Building a Sustainable Healthcare Exchange between the Netherlands and Cuba.

Over the past ten years, seven Dutch Universities have built a sustainable exchange with seven institutes in Cuban healthcare. The exchange was initiated by the Leiden University Medical Centre and the University of Medical Sciences of Havana. Cooperation with Cuba was chosen as Cuba has excellent primary healthcare and has a strong focus on prevention and public health. These were considered important due to the major contribution of non-communicable diseases to morbidity and mortality in the Netherlands. Exchanges have occurred with Dutch health professionals and students visiting Cuban healthcare institutions and Cuban postgraduate students studying in the Netherlands. There has been an increased awareness of the importance of public health and prevention in Dutch professional organizations following the exchange. The exchange has also helped to break the scientific and economic US blockade of Cuba and resulted in joint publications. In this review we described the process, key aspects, results and lessons learned in this process. Collaboration between Cuba (a middle income) and the Netherlands (a high-income country) is possible.

Management of patent ductus arteriosus in very preterm infants in England and Wales: a retrospective cohort study.

OBJECTIVE: To describe the diagnosis and treatment of patent ductus arteriosus (PDA) in infants born at <32 weeks' gestational age (GA) in England and Wales between 2010 and 2017. STUDY DESIGN: Retrospective cohort study using routinely recorded data from the National Neonatal Research Database of infants born at <32 weeks admitted to neonatal units in England and Wales from 2010 to 2017. RESULTS: Among 58 108 infants born at <32 weeks' GA, 28.3% (n=16 440) had a PDA diagnosed clinically or with echocardiographic confirmation. Of these, 34.8% (n=5721; 9.8% of total <32 weeks' infants included) had PDA treatment including 7.6% (n=1255) with indomethacin, 23.5% (n=3857) with ibuprofen and 5.6% (n=916) with surgical closure. The highest incidence of PDA was among infants born at 24 and 25 weeks' GA (70.2% and 70.8%, respectively), decreasing to 6.1% among infants born at 31 weeks' GA. The percentage of infants with a PDA increased over the study period (25.5% in 2010 to 28.5% in 2017). The percentage of infants who received ibuprofen or indomethacin or had PDA surgery decreased from 41.3% in 2010 to 33.7% in 2017, with an increase in use of ibuprofen from 20.2% to 27.3% while use of indomethacin decreased from 20.0% to 8.8%. Surgical closure of PDA decreased from 9.1% to 3.0%. Indomethacin was used for median (IQR) 3 (2-5) days while ibuprofen was given for 3 (2-4) days, at a median of 8 and 10 days after birth, respectively; surgical treatment was used later at 33 (24-45) days after birth. CONCLUSIONS: Ibuprofen is the preferred drug and surgical interventions are becoming less frequent for PDA closure among very preterm infants in England and Wales. TRIAL REGISTRATION NUMBER: NCT03773289.

Secondary Effects from Mass Azithromycin Administration: A Systematic Review and Meta-analysis.

The effects of azithromycin mass drug administration (MDA) on trachoma and yaws have been addressed. However, the secondary effects of azithromycin MDA remain unclear. This study aimed to explore the secondary effects of azithromycin MDA. PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from conception to January 5, 2022. Studies on secondary effects of azithromycin MDA were included. A total of 34 studies were included. Six of them reported on child mortality, 10 on malaria, and 20 on general morbidity and condition. Azithromycin MDA reduced child mortality, and quarterly MDA may be most beneficial for reducing child mortality. The effect of azithromycin MDA on malaria was weak. No association was observed between azithromycin MDA and malaria parasitemia (rate ratio: 0.71, 95% confidence interval: 0.43-1.15). Azithromycin MDA was associated with a lower risk of respiratory tract infections and diarrhea. Additionally, it was associated with a lower risk of fever, vomiting, and headache. The carriage of pathogenic organisms such as Streptococcus pneumoniae and gut Campylobacter species was reduced. However, these secondary effects of azithromycin MDA appeared to last only a few weeks. Moreover, no association was observed between azithromycin MDA and nutritional improvement in children. In conclusion, azithromycin MDA had favorable secondary effects on child mortality and morbidity. However, the effects were short term.

Accessibility of Essential Medicines for Children in Sichuan Province of China: A Cross-Sectional Study.

Background: Essential medicines for children are those medicines that satisfy the priority health care needs of children. Access to essential medicines for children is a big challenge, particularly in low- and middle-income countries. Our study aimed to assess the accessibility of essential medicines for children in public sector in Sichuan Province of China, based on availability, affordability, and price. Methods: We adopted the modified World Health Organization/Health Action International (WHO/HAI) standardization methodology to measure the availability, affordability, and prices of 30 essential medicines for children in 20 public hospitals in nine regions of the Sichuan Province, China. Availability was expressed as the percentage of public medicine outlets that stocked surveyed medicines on the day of data collection, and prices were expressed as median price ratio (MPR). Affordability was assessed as the number of Sichuan Province's daily wages required for the lowest-paid government unskilled worker (11.03 USD per day) to purchase one standard treatment of an acute disease or treatment for chronic disease for a month. Results: The mean availability of originator brands (OBs) and lowest priced generics (LPGs) were 9.7 and 46.5% in public sector. MPRs of only 3 OBs could be calculated, ranging from 0.55 to 13.37. MPRs of 18 LPGs ranged from 0.07 to 25.05. Among them, 2 OBs and 11 LPGs were priced at more than 1.5 times their international reference prices (IRPs) in public sector, most of which were injections. Except for cefazolin injection and ceftriaxone injection, most LPGs were affordable for the treatment of childhood diseases in public sector, as they each cost one or less than the daily wage for the lowest-paid unskilled government worker. Conclusions: Although the availability of LPGs for children was higher than OBs in public sector, the availability of children's essential medicines was low in surveyed public sector in Sichuan Province, which was similar to previous studies in other provinces of China. The price of most medicines surveyed was higher than their IRPs in surveyed public sector, especially for some injections. The affordability of most surveyed LPGs was reasonable in surveyed public sector, except for ceftriaxone injection and cefazolin injection.

Drug utilisation in neonatal units in England and Wales: a national cohort study.

PURPOSE: To describe drug utilisation patterns in neonatal units. METHODS: Retrospective observational cohort study using data held in the National Neonatal Research Database (NNRD) for neonatal units in England and Wales including infants born at 23 to 44 weeks' gestational age (GA) from 01 January 2010 to 31 December 2017. RESULTS: The cohort included 17,501 (3%) extremely preterm infants; 40,607 (7%) very preterm infants; 193,536 (31%) moderate-to-late preterm infants; and 371,606 (59%) term infants. The number of unique drugs received by an infant (median (IQR)) increased with decreasing GA: 17 (11-24) in extremely preterm, 7 (5-11) in very preterm, 3 (0-4) in moderate-to-late preterm, and 3 (0-3) in term infants. The two most frequently prescribed drugs were benzylpenicillin and gentamicin in all GA groups, and caffeine in extremely preterm. Other frequently used drugs among preterm infants were electrolytes, diuretics and anti-reflux medications. Among infants <32 weeks' GA, the largest increase in use was for surfactant (given on the neonatal unit), caffeine and probiotics, while domperidone and ranitidine had the largest decline. CONCLUSION: Antibiotics, for all GAs and caffeine, among preterm infants, are the most frequently used drugs in neonatal medicine. Preterm infants are exposed to a high burden of drugs, particularly antibiotics. Changing patterns in use reflect the emergence of evidence in some areas but several non-evidence-based drugs continue to be used widely. Improvements are needed to ensure rational drug use on neonatal units. REGISTRATION: ClinicalTrials.gov (NCT03773289). Date of registration 21 Dec 2018.

Access to medicines for children in China.

Access to essential medicines for children is a big challenge, particularly in low-income and middle-income countries. In China, the average availability of essential medicines for children is 1.6%-46.5%. The availability of generics was generally higher than original brands in public hospitals and the prices of generics were relatively lower and more reasonable (generics: availability, 27.3%-46.5%, prices, 0.52-4.28 times the international reference prices; original brands: 1.6%-33.0%, 2.59-11.38 times the international reference prices). In terms of affordability of medicines for children, generics were more affordable than original brands and tablets/capsules were more affordable than injections. Most commonly used anti-infective medicines (such as amoxicillin capsule, azithromycin tablet, cefuroxime tablet) and antipyretics (such as ibuprofen suspension) were relatively affordable. Six commonly used medicines in paediatrics, including amoxicillin/clavulanic acid, beclomethasone, cefazolin, ceftazidime, ceftriaxone, cyclosporine were unaffordable. Since August 2011, China has successively issued several policies to ensure the accessibility of medicines for children, covering research and development, production, procurement and prices of medicines. The accessibility of medicines for children has been partially improved, but still needs continuous improvement.

Climate Change and Child Health Inequality: A Review of Reviews.

There is growing evidence on the observed and expected consequences of climate change on population health worldwide. There is limited understanding of its consequences for child health inequalities, between and within countries. To examine these consequences and categorize the state of knowledge in this area, we conducted a review of reviews indexed in five databases (Medline, Embase, Web of Science, PsycInfo, Sociological Abstracts). Reviews that reported the effect of climate change on child health inequalities between low- and high-income children, within or between countries (high- vs low-middle-income countries; HICs and LMICs), were included. Twenty-three reviews, published between 2007 and January 2021, were included for full-text analyses. Using thematic synthesis, we identified strong descriptive, but limited quantitative, evidence that climate change exacerbates child health inequalities. Explanatory mechanisms relating climate change to child health inequalities were proposed in some reviews; for example, children in LMICs are more susceptible to the consequences of climate change than children in HICs due to limited structural and economic resources. Geographic and intergenerational inequalities emerged as additional themes from the review. Further research with an equity focus should address the effects of climate change on adolescents/youth, mental health and inequalities within countries.

Effectiveness of azithromycin mass drug administration on trachoma: a systematic review.

BACKGROUNDS: Azithromycin mass drug administration (MDA) is a key part of the strategy for controlling trachoma. This systematic review aimed to comprehensively summarize the present studies of azithromycin MDA on trachoma; provide an overview of the impact of azithromycin MDA on trachoma in different districts; and explore the possible methods to enhance the effectiveness of azithromycin MDA in hyperendemic districts. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched up to February 2021 with no language restriction. Studies reporting the effect of azithromycin MDA on trachoma were included. Mathematical modeling studies, animal studies, case reports, and reviews were excluded. The trachomatous inflammation-follicular (TF) <5.0% was used to judge the effect of azithromycin MDA on eliminating trachoma as a public health problem. Two researchers independently conducted the selection process and risk of bias assessment. RESULTS: A total of 1543 studies were screened, of which 67 studies including 13 cluster-randomized controlled trials and 54 non-randomized studies were included. The effect of azithromycin MDA on trachoma was closely related to the baseline prevalence in districts. For the districts with baseline prevalence between 5.0% and 9.9%, a single round of MDA achieved a TF <5.0%. For the districts with baseline between 10.0% and 29.9%, annual MDA for 3 to 5 years reduced TF <5.0%. However, for the districts with high level of baseline prevalence (TF >30.0%), especially with baseline TF >50.0%, annual MDA was unable to achieve the TF <5.0% even after 5 to 7 years of treatment. Quarterly MDA is more effective in controlling trachoma in these hyperendemic districts. CONCLUSIONS: Azithromycin MDA for controlling trachoma depends on the baseline prevalence. The recommendation by the World Health Organization that annual MDA for 3 to 5 years in the districts with TF baseline >10.0% is not appropriate for all eligible districts.

Accessibility of Medicines for Children: A Systematic Review.

Background: Accessibility of medicines for children is a matter of global concern. Medicines prescribed for children are often off-label. To formulate appropriate policies and undertake necessary interventions to improve access to medicines for children, it is necessary to evaluate the accessibility of medicines for children. However, there is no systematic review of the medicine accessibility for children. Methods: Relevant studies were identified through searching Pubmed, Embase, CNKI, Wanfang, VIP, World Health Organization website, and Health Action International website. Besides, the references of included studies as a supplementary search were read. We extracted the basic information of articles (the first author, published year, the name of journal, research institution, etc.), the basic study characteristics (survey area, survey time, survey method, survey medicine lists, the number of medicine outlets surveyed, etc.), and the study results (the current situation of the accessibility of medicines for children, including the availability, price, and affordability of medicines for children, etc.). Two reviewers independently selected studies and extracted the data. Descriptive analysis methods to analyze the current situation of the accessibility of children's medicines were used. Results: A total of 18 multicenter cross-sectional studies were included in this systematic review, which were from low-income and middle-income countries. Seventeen studies (17/18, 94.4%) used the WHO/Health Action International (HAI) medicine price methodology to investigate the accessibility of medicines for children. Fifteen studies (15/18, 83.3%) were selected to investigate medicines based on the WHO Model List of Essential Medicines for Children (WHO EMLc). In the public sectors, the availability of originator brands (OBs) ranged from 0 to 52.0%, with a median of 24.2%, and the availability of lowest-priced generics (LPGs) ranged from 17.0 to 72.6%, with a median of 38.1%. In the private sectors, the availability of OBs ranged from 8.9 to 80%, with a median of 21.2%. The availability of LPGs ranged from 20.6 to 72.2%, with a median of 35.9%. In most regions, the availability of OBs in the private sectors was higher than in the public sectors. Collectively, in the price of medicines for children, the median price ratio (MPR) of the OBs in the public sectors and private sectors were much higher than that of the LPGs. And the affordability of the LPGs in the public sectors and private sectors was higher than that of originator brands (OBs). Conclusion: The availability of medicines for children is low in both the public sectors and private sectors in low-income and middle-income countries. The MPR of originator brands (OBs) is higher than that of lowest-priced generics (LPGs), and the most lowest-priced generics (LPGs) have better affordability.

Arms sales and child health.

The adverse effects of armed conflict on child health are well recognised. The relationships among the arms trade, armed conflict and child health are less clearly defined. The arms trade is one of the largest industries in the world (total expenditure US$1917 billion in 2019), generating colossal profits to private companies and individuals at the expense of taxpayers throughout the world. The money wasted on weapons designed to kill and maim should be used for more socially useful products, such as clean water, food, health and education. The sustainable development goals can be funded by diverting money from the arms companies. Health professionals and their organisations have a responsibility to children to try and curb the ever-expanding arms industry.

Review of Drug Utilization Studies in Neonatal Units: A Global Perspective.

Rational prescribing is challenging in neonatology. Drug utilization studies help identify and define the problem. We performed a review of the literature on drug use in neonatal units and describe global variations. We searched databases (EMBASE, CINAHL and Medline) from inception to July 2020, screened studies and extracted relevant data (two reviewers). The search revealed 573 studies of which 84 were included. India (n = 14) and the USA (n = 13) reported the most. Data collection was prospective (n = 56) and retrospective (n = 26), mostly (n = 52) from one center only. Sixty studies described general drug use in 34 to 450,386 infants (median (IQR) 190 (91-767)) over a median (IQR) of 6 (3-18) months. Of the participants, 20-87% were preterm. The mean number of drugs per infant (range 11.1 to 1.7, pooled mean (SD) 4 (2.4)) was high with some reporting very high burden (≥30 drugs per infant in 8 studies). This was not associated with the proportion of preterm infants included. Antibiotics were the most frequently used drug. Drug use patterns were generally uniform with some variation in antibiotic use and more use of phenobarbitone in Asia. This study provides a global perspective on drug utilization in neonates and highlights the need for better quality information to assess rational prescribing.