Baseline assessment of WHO's target for both availability and affordability of essential medicines to treat non-communicable diseases

Background: WHO has set a voluntary target of 80% availability of affordable essential medicines, including generics, to treat major non-communicable diseases (NCDs), in the public and private sectors of countries by 2025. We undertook a secondary analysis of data from 30 surveys in low- and middle-income countries, conducted from 2008-2015 using the World Health Organization (WHO)/Health Action International (HAI) medicine availability and price survey methodology, to establish a baseline for this target. Methods Data for 49 medicines (lowest priced generics and originator brands) to treat cardiovascular diseases (CVD), diabetes, chronic obstructive pulmonary diseases (COPD) and central nervous system (CNS) conditions were analysed to determine their availability in healthcare facilities and pharmacies, their affordability for those on low incomes (based on median patient prices of each medicine), and the percentage of medicines that were both available and affordable. Affordability was expressed as the number of days' wages of the lowestpaid unskilled government worker needed to purchase 30 days' supply using standard treatment regimens. Paying more than 1 days' wages was considered unaffordable. Findings In low-income countries, 15.2% and 18.9% of lowest-priced generics met WHO's target in the public and private sectors, respectively, and 2.6% and 5.2% of originator brands. In lower-middle income countries, 23.8% and 23.2% of lowest priced generics, and 0.8% and 1.4% of originator brands, met the target in the public and private sectors, respectively. In upper-middle income countries, the situation was better for generics but still suboptimal as 36.0% and 39.4% met the target in public and private sectors, respectively. For originator brands in upper-middle income countries, none reached the target in the public sector and 13.7% in the private sector. Across the therapeutic groups for lowest priced generics, CVD medicines in low-income countries (11.9%), and CNS medicines in lower-middle (10.2%) and upper-middle income countries (33.3%), were least available and affordable in the public sector. In the private sector for lowest priced generics, CNS medicines were least available and affordable in all three country income groups (11.4%, 5.8% and 29.3% in low-, lower-middle and upper-middle income countries respectively). Interpretation This data, which can act as a baseline for the WHO target, shows low availability and/or poor affordability is resulting in few essential NCD medicines meeting the target in low- and middle-income countries. In the era of Sustainable Development Goals, and as countries work to achieve Universal Health Coverage, increased commitments are needed by governments to improve the situation through the development of evidence-informed, nationallycontextualised interventions, with regular monitoring of NCD medicine availability, patient prices and affordability.IS

ATP13A2 deficiency disrupts lysosomal polyamine export

ATP13A2 (PARK9) is a late endolysosomal transporter that is genetically implicated in a spectrum of neurodegenerative disorders, including Kufor-Rakeb syndrome—a parkinsonism with dementia1—and early-onset Parkinson’s disease2. ATP13A2 offers protection against genetic and environmental risk factors of Parkinson’s disease, whereas loss of ATP13A2 compromises lysosomes3. However, the transport function of ATP13A2 in lysosomes remains unclear. Here we establish ATP13A2 as a lysosomal polyamine exporter that shows the highest affinity for spermine among the polyamines examined. Polyamines stimulate the activity of purified ATP13A2, whereas ATP13A2 mutants that are implicated in disease are functionally impaired to a degree that correlates with the disease phenotype. ATP13A2 promotes the cellular uptake of polyamines by endocytosis and transports them into the cytosol, highlighting a role for endolysosomes in the uptake of polyamines into cells. At high concentrations polyamines induce cell toxicity, which is exacerbated by ATP13A2 loss due to lysosomal dysfunction, lysosomal rupture and cathepsin B activation. This phenotype is recapitulated in neurons and nematodes with impaired expression of ATP13A2 or its orthologues. We present defective lysosomal polyamine export as a mechanism for lysosome-dependent cell death that may be implicated in neurodegeneration, and shed light on the molecular identity of the mammalian polyamine transport system

The AppNL-G-F mouse retina is a site for preclinical Alzheimer's disease diagnosis and research

In this study, we report the results of a comprehensive phenotyping of the retina of the AppNL-G-F mouse. We demonstrate that soluble Aβ accumulation is present in the retina of these mice early in life and progresses to Aβ plaque formation by midlife. This rising Aβ burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings revealed signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unafected in the AppNL-G-F mouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aβ, underscoring its potential as a biomarker for AD diagnosis and monitoring. These fndings suggest that the AppNL-G-F retina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, ofers unique opportunities for drug discovery and fundamental research into preclinical AD

Availability, price and affordability of cardiovascular medicines: A comparison across 36 countries using WHO/HAI data

<p>Abstract</p> <p>Background</p> <p>The global burden of cardiovascular disease (CVD) continues to rise. Successful treatment of CVD requires adequate pharmaceutical management. The aim was to examine the availability, pricing and affordability of cardiovascular medicines in developing countries using the standardized data collected according to the World Health Organization/Health Action International methodology.</p> <p>Methods</p> <p>The following medicines were included: atenolol, captopril, hydrochlorothiazide, losartan and nifedipine. Data from 36 countries were analyzed. Outcome measures were percentage availability, price ratios to international reference prices and number of day's wages needed by the lowest-paid unskilled government worker to purchase one month of chronic treatment. Patient prices were adjusted for inflation and purchasing power, procurement prices only for inflation. Data were analyzed for both generic and originator brand products and the public and private sector and summarized by World Bank Income Groups.</p> <p>Results</p> <p>For all measures, there was great variability across surveys. The overall availability of cardiovascular medicines was poor (mean 26.3% in public sector, 57.3% private sector). Procurement prices were very competitive in some countries, whereas others consistently paid high prices. Patient prices were generally substantially higher than international references prices; some countries, however, performed well. Chronic treatment with anti-hypertensive medication cost more than one day's wages in many cases. In particular when monotherapy is insufficient, treatment became unaffordable.</p> <p>Conclusions</p> <p>The results of this study emphasize the need of focusing attention and financing on making chronic disease medicines accessible, in particular in the public sector. Several policy options are suggested to reach this goal.</p

Emma Gelders Sterne papers, W.0099

Abstract: Contracts and business correspondence related to the publication of books written by Alabama author Emma Gelders Sterne.Scope and Content Note: This collection contains contracts and business correspondence between Alabama author Emma Gelders Sterne and her publishers at Dodd, Mead, and Company. The correspondence and contracts are dated from 1934 to 1953 and mostly include republication agreements between Sterne and the publishers. The collection includes materials related to The Calico Ball, Some Plant Olive Trees, and Drums of Monmouth.Biographical/Historical Note: Emma Gelders Sterne was born on May 13, 1894, in Birmingham, Alabama. She graduated from Smith College in 1916, receiving a BA. After college, Sterne returned to Birmingham, where she was involved in a number of activist efforts, including the suffrage movement.In 1917, she married lawyer Roy M. Sterne; the couple had two daughters, Ann and Barbara. The family moved to New York, where Roy worked for the Liggett Drug Company and Emma became involved in a number of activist groups, including the National Association for the Advancement of Colored People and the American Civil Liberties Union.A prolific children's author, Sterne published a total of forty-four books during a literary career that spanned four decades. Several of her books, including No Surrender, Amarantha Gay, M.D., and The Calico Ball are set in Birmingham; another work, Some Plant Olive Trees, was inspired by the French settlement of Demopolis, Alabama.Sterne spent her final years in California; she died on August 29, 1971, in San Jose.Source: Encyclopedia of Alabam