Aberrant DNA methylation of hypothalamic angiotensin receptor in prenatal programmed hypertension.

Maternal malnutrition, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming, leading to hypertension in offspring. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, a synthetic glucocorticoid, mRNA expression of angiotensin receptor type 1a (Agtr1a) in the paraventricular nucleus (PVN) of the hypothalamus was upregulated, concurrent with reduced expression of DNA methyltransferase 3a (Dnmt3a), reduced binding of DNMT3a to the Agtr1a gene, and DNA demethylation. Salt loading increased BP in both types of offspring, suggesting that elevated hypothalamic Agtr1a expression is epigenetically modulated by excessive glucocorticoid and leads to adult-onset salt-sensitive hypertension. Consistent with this, dexamethasone treatment of PVN cells upregulated Agtr1a, while downregulating Dnmt3a, and decreased DNMT3a binding and DNA demethylation at the Agtr1a locus. In addition, Dnmt3a knockdown upregulated Agtr1a independently of dexamethasone. Hypothalamic neuron-specific Dnmt3a-deficient mice exhibited upregulation of Agtr1a in the PVN and salt-induced BP elevation without dexamethasone treatment. By contrast, dexamethasone-treated Agtr1a-deficient mice failed to show salt-induced BP elevation, despite reduced expression of Dnmt3a. Thus, epigenetic modulation of hypothalamic angiotensin signaling contributes to salt-sensitive hypertension induced by prenatal glucocorticoid excess in offspring of mothers that are malnourished during pregnancy.

The availability, pricing and affordability of three essential asthma medicines in 52 low- and middle-income countries.

BACKGROUND: Almost 300 million people suffer from asthma, yet many in low- and middle-income countries have difficulty accessing essential asthma medicines. Availability, price and affordability of medicines are likely to affect access. Very few studies have included asthma medicines, particularly inhaled corticosteroids, in these countries. Reflections about international reference prices (IRPs) are generally absent from pricing studies, yet some IRPs may be masking the extent of access problems. OBJECTIVES: Our objective was to determine the availability, pricing and affordability of beclometasone, budesonide and salbutamol, the three asthma medicines on the World Health Organization's Model List of Essential Medicines (EML) in selected low- and middle-income countries and to reflect on the appropriateness of using IRPs. METHODS: A cross-sectional pricing survey was conducted in 52 countries. Data were collected on country demographics including national currency, $US exchange rate and daily wage of the lowest-paid unskilled government worker. Pricing and availability data were collected for salbutamol, beclometasone and budesonide in two private retail pharmacies, the national procurement centre and a main public hospital. RESULTS: Availability was particularly poor for corticosteroids, and worse in national procurement centres and main hospitals. The surveyed strength of beclometasone was only on the EML of ten countries. Considerable variability was found in pricing and affordability across countries. Procurement systems appeared largely inefficient when Asthma Drug Facility prices were applied as references. Some countries appear to be subsidising asthma medicines, making them free or less expensive for patients, while other countries are applying very high margins, which can significantly increase the price for patients unless a reimbursement system exists. CONCLUSIONS: Findings raise important policy concerns. Availability of inhaled corticosteroids is poor; many EMLs are not updated; IRPs can be misleading; health systems and patients are paying more than necessary for asthma medicines, which are unaffordable for many patients in many countries.

Use of antenatal corticosteroids for preterm birth in Latin America: providers knowledge, attitudes and practices.

BACKGROUND: Antenatal corticosteroids administered to women at risk of preterm birth is an intervention which has been proved to reduce the risk of respiratory distress syndrome, intraventricular hemorrhage, and neonatal mortality. There is a significant gap in the literature regarding the prevalence of the use of antenatal corticosteroids in Latin American countries and the attitudes and opinions of providers regarding this practice. The aim of this study was to assess the knowledge, attitudes and practices of health care providers regarding the use of antenatal corticosteroids in women at risk of preterm birth in Latin America. METHODS: This was a multicenter, prospective, descriptive study conducted in maternity hospitals in Ecuador, El Salvador, Mexico and Uruguay. Physicians and midwives who provide prenatal care or intrapartum care for women delivering in the selected hospitals were approached using a self-administered questionnaire. Descriptive statistics was used. RESULTS: The percentage of use of ACT in threatened preterm labour (TPL) reported by providers varies from 70% in Mexico to 97% in Ecuador. However, 60% to 20% of the providers mentioned that they would not use this medication in women at risk and would limit its use when there was a threatened preterm labour. In only one country recommended regimens of antenatal corticosteroids are followed by around 90% of providers whereas in the other three countries recommended regimens are followed by only 21%, 61%, 69% of providers. Around 40% of providers mentioned that they would administer a new dose of corticosteroids again, regardless the patient already receiving an entire regimen. Between 11% and 35% of providers, according to the countries, mentioned that they do not have adequate information on the correct use of this medication. CONCLUSIONS: This study shows that the use of this intervention could be improved by increasing the knowledge of Latin American providers on its indications, benefits, and regimens.

Computerized reminders reduce the use of medications during shortages.

Medication shortages pose serious problems in health care. This study examines the impact of a computer-based reminder in addressing a national methylprednisolone shortage. An alert was designed and implemented in a computerized order entry platform at a children's hospital. The alert informed physicians of the shortage and provided an alternative prescribing pathway. Data regarding the number and type of parenteral corticosteroid prescriptions were collected for a one-month period before and after the alert was implemented. The alert resulted in a 55% relative reduction in methylprednisolone use and an average reduction of more than three orders each day. Dexamethasone and hydrocortisone, the recommended alternative medications, increased in use by 12% and 49%, respectively. The alert resulted in a $36,552 annualized cost reduction to the institution. Similar alert applications have great potential for effectively altering physician prescribing behavior.