Mother-Baby Friendly Philippines: Using Citizen Reporting to Improve Compliance to the International Code of Marketing of Breastmilk Substitutes.

INTRODUCTION: In 1986, the Philippines was one of the first countries to pass national legislation on the International Code of Marketing of Breastmilk Substitutes in the form of Executive Order (EO) 51 and Republic Act (RA) 10028. While violations against the legislation and corresponding sanctions are clearly defined, infractions remain unreported or go unpunished. Enforcement of the laws remains a significant challenge as government capacities suffer from inadequate resources to regularly monitor breastfeeding-related law violations. To address these gaps, The Department of Health (Philippines) and the World Vision Development Foundation developed a reporting platform to enable citizen reporting of EO 51 and RA 10028 violations as part of the Mother-Baby Friendly Philippines (MBFP) initiative. METHODS: Upon completion of the project, the Alliance for Improving Health Outcomes Inc. conducted 68 surveys and 24 key informant interviews and focus group discussions with individuals who participated in trainings on EO 51 and RA 10028, community health workers, representatives of local government units and hospitals involved in breastfeeding programs, and city health officials to document benefits, challenges, and lessons learned. RESULTS: The intention and interest of consulted stakeholders to uphold the law by reporting violations through the platform indicate that citizen reporting can be harnessed as an effective tool for reporting violations. Nevertheless, multiple challenges remain in reporting and following up on Code violations. DISCUSSION: The platform provided citizens with an opportunity to report violations, but, in reality, the status of action and feedback did not change. There is a need to strengthen implementation and enforcement at all levels of relevant national government agencies and improve feedback loops on reported violations.

Breastfeeding, first-food systems and corporate power: a case study on the market and political practices of the transnational baby food industry and public health resistance in the Philippines.

BACKGROUND: The aggressive marketing of breastmilk substitutes (BMS) reduces breastfeeding, and harms child and maternal health globally. Yet forty years after the World Health Assembly adopted the International Code of Marketing of Breast-milk Substitutes (The Code), many countries are still to fully implement its provisions into national law. Furthermore, despite The Code, commercial milk formula (CMF) markets have markedly expanded. In this paper, we adopt the Philippines as a case study to understand the battle for national Code implementation. In particular, we investigate the market and political strategies used by the baby food industry to shape the country's 'first-food system', and in doing so, promote and sustain CMF consumption. We further investigate how breastfeeding coalitions and advocates have resisted these strategies, and generated political commitment for a world-leading breastfeeding policy framework and protection law (the 'Milk Code'). We used a case study design and process tracing method, drawing from documentary and interview data. RESULTS: The decline in breastfeeding in the Philippines in the mid-twentieth Century associated with intensive BMS marketing via health systems and consumer advertising. As regulations tightened, the industry more aggressively promoted CMFs for older infants and young children, thereby 'marketing around' the Milk Code. It established front groups to implement political strategies intended to weaken the country's breastfeeding policy framework while also fostering a favourable image. This included lobbying government officials and international organizations, emphasising its economic importance and threats to foreign investment and trade, direct litigation against the government, messaging that framed marketing in terms of women's choice and empowerment, and forging partnerships. A resurgence in breastfeeding from the mid-1980s onwards reflected strengthening political commitment for a national breastfeeding policy framework and Milk Code, resulting in-turn, from collective actions by breastfeeding coalitions, advocates and mothers. CONCLUSION: The Philippines illustrates the continuing battle for worldwide Code implementation, and in particular, how the baby food industry uses and adapts its market and political practices to promote and sustain CMF markets. Our results demonstrate that this industry's political practices require much greater scrutiny. Furthermore, that mobilizing breastfeeding coalitions, advocacy groups and mothers is crucial to continually strengthen and protect national breastfeeding policy frameworks and Code implementation.

Detection and Genome Sequencing of SARS-CoV-2 Variants Belonging to the B.1.1.7 Lineage in the Philippines.

We report the sequencing and detection of 36 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage in the Philippines.

Effects of Rifampin on the Pharmacokinetics of a Single Dose of Istradefylline in Healthy Subjects.

Istradefylline, a selective adenosine A2A inhibitor, is under development for the treatment of Parkinson's disease. The effect of oral steady-state rifampin 600 mg/day, a potent cytochrome P450 (CYP) 3A4 inducer, on the disposition of a single oral dose of istradefylline 40 mg was determined in a crossover study in 20 healthy subjects by measuring plasma concentrations of istradefylline and its M1 and M8 metabolites and their derived pharmacokinetic parameters. Based on the geometric mean ratio of log-transformed data, rifampin reduced istradefylline exposure: Cmax , 0.55 (90%CI, 0.49-0.62); AUClast , 0.21 (90%CI, 0.19-0.22); and AUCinf , 0.19 (90%CI, 0.18-0.20), indicating nonequivalence. These changes were primarily because of the effect of rifampin on the elimination parameters of istradefylline; mean CL/F was increased from 4.0 to 20.6 L/h, and mean t1/2 was reduced from 94.8 to 31.5 hours. The effect of rifampin coadministration on the disposition of the istradefylline M1 and M8 metabolites was inconsistent and variable. Furthermore, as exposure of the istradefylline M1 and M8 metabolites in plasma was generally <9% of total drug exposure, it would be expected to have a negligible impact on the pharmacodynamic effect of istradefylline. Caution should be exercised when istradefylline is administered concurrently with strong CYP3A4 inducers and dose adjustment considered.

Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23). OBJECTIVE: Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody. METHODS: Twenty-eight adult outpatients with XLH received up to four doses of KRN23 administered subcutaneously every 28 days. General HRQoL was measured with the SF-36v2 and condition-related HRQoL with the WOMAC at baseline and study endpoint as a secondary outcome of a Phase 1/2, open-label, multicenter, dose-escalation trial. RESULTS: Testing for scale discriminant validity and convergent-divergent validity supported the use of these scales in the assessment of HRQoL in XLH. Both instruments indicated impairment of physical function at baseline with all mean scores showing a trend to improved health at study endpoint compared to baseline. When corrected for multiple comparisons, the score for Role Limitations due to physical health on the SF-36v2 which measures the patient's perception of their own chronic functional impairments due to poor physical health remained significantly improved (P < 0.05), increasing to the mean score of US adults. For the WOMAC, Physical Functioning and Stiffness scores were significantly improved (P < 0.05). CONCLUSION: KRN23 administration was associated with significantly improved patient perception of their Physical Functioning and Stiffness due to their disease. This study demonstrates that the SF-36v2 and WOMAC are valid tools for assessing HRQoL in XLH.

Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia.

In X-linked hypophosphatemia (XLH), serum fibroblast growth factor 23 (FGF23) is increased and results in reduced renal maximum threshold for phosphate reabsorption (TmP), reduced serum inorganic phosphorus (Pi), and inappropriately low normal serum 1,25 dihydroxyvitamin D (1,25[OH]2 D) concentration, with subsequent development of rickets or osteomalacia. KRN23 is a recombinant human IgG1 monoclonal antibody that binds to FGF23 and blocks its activity. Up to 4 doses of KRN23 were administered subcutaneously every 28 days to 28 adults with XLH. Mean ± standard deviation KRN23 doses administered were 0.05, 0.10 ± 0.01, 0.28 ± 0.06, and 0.48 ± 0.16 mg/kg. The mean time to reach maximum serum KRN23 levels was 7.0 to 8.5 days. The mean KRN23 half-life was 16.4 days. The mean area under the concentration-time curve (AUCn ) for each dosing interval increased proportionally with increases in KRN23 dose. The mean intersubject variability in AUCn ranged from 30% to 37%. The area under the effect concentration-time curve (AUECn ) for change from baseline in TmP per glomerular filtration rate, serum Pi, 1,25(OH)2 D, and bone markers for each dosing interval increased linearly with increases in KRN23 AUCn . Linear correlation between serum KRN23 concentrations and increase in serum Pi support KRN23 dose adjustments based on predose serum Pi concentration.

Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23.

CONTEXT: In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia. OBJECTIVE: The objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH. DESIGN: Two sequential open-label phase 1/2 studies were done. SETTING: Six academic medical centers were used. PARTICIPANTS: Twenty-eight adults with XLH participated in a 4-month dose-escalation study (0.05-0.6 mg/kg); 22 entered a 12-month extension study (0.1-1 mg/kg). INTERVENTION: KRN23 was injected sc every 28 days. MAIN OUTCOME MEASURE: The main outcome measure was the proportion of subjects attaining normal serum Pi and safety. RESULTS: At baseline, mean TmP/GFR, serum Pi, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 1.6 ± 0.4 mg/dL, 1.9 ± 0.3 mg/dL, and 36.6 ± 14.3 pg/mL, respectively. During dose escalation, TmP/GFR, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi and at 3-7 days for 1,25(OH)2D, remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] pre-dose levels at trough. After each of the four escalating doses, peak Pi was between 2.5 and 4.5 mg/dL in 14.8, 37.0, 74.1, and 88.5% of subjects, respectively. During the 12-month extension, peak Pi was in the normal range for 57.9-85.0% of subjects, and ≥25% maintained trough Pi levels within the normal range. Serum Pi did not exceed 4.5 mg/dL in any subject. Although 1,25(OH)2D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover and had a favorable safety profile. CONCLUSIONS: Monthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects. KRN23 has potential for effectively treating XLH.