The Graying of American Debt

Between 2003 and 2015, real aggregate debt in the hands of Americans aged 50 to 80 increased by 59 percent. Meanwhile, real debt held by Americans in their twenties and thirties was approximately flat. Using data from the Federal Reserve Bank of New York’s Consumer Credit Panel, we describe the extent of this debt increase and the distribution of debt growth by loan type. Real per capita home-secured debts held by older consumers show the steepest growth, though older borrowers have increased their obligations in all major debt categories. For long-held debts, these developments lead us to ask how such changes emerged: did older borrowers carry more debt through the Great Recession, after which access to consumer credit declined for new borrowers of all ages? Alternatively, have loan originations since the Great Recession favored older over younger borrowers? While our results indicate that the stock of long-held, home-secured debt sits largely with older borrowers, we also uncover evidence of a decisive tilt of new auto and mortgage originations away from younger borrowers and toward borrowers in their fifties, sixties, and even seventies. The motivation behind older consumers’ substantial new borrowing, often with long repayment terms, is the focus of ongoing research

The independent effect of living in malaria hotspots on future malaria infection: an observational study from Misungwi, Tanzania.

BACKGROUND: As malaria transmission declines, continued improvements of prevention and control interventions will increasingly rely on accurate knowledge of risk factors and an ability to define high-risk areas and populations at risk for focal targeting of interventions. This paper explores the independent association between living in a hotspot and prospective risk of malaria infection. METHODS: Malaria infection status defined by nPCR and AMA-1 status in year 1 were used to define geographic hotspots using two geospatial statistical methods (SaTScan and Kernel density smoothing). Other malaria risk factors for malaria infection were explored by fitting a multivariable model. RESULTS: This study demonstrated that residing in infection hotspot of malaria transmission is an independent predictor of malaria infection in the future. CONCLUSION: It is likely that targeting such hotspots with better coverage and improved malaria control strategies will result in more cost-efficient uses of resources to move towards malaria elimination

Impact of malaria and helminth infections on immunogenicity of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Tanzania.

BACKGROUND: Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators and impact responses to standard immunizations. We conducted a cohort study to measure the influence of malaria and helminth infections on the immunogenicity of the bivalent HPV-16/18 vaccine. METHODS: We evaluated the association between malaria and helminth infections, and HPV-16/18 antibody responses among 298 Tanzanian females aged 10-25 years enrolled in a randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was diagnosed by examination of blood smears, and helminth infections were diagnosed by examination of urine and stool samples, respectively. Geometric mean antibody titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Parasitic infections were common; one-third (30.4%) of participants had a helminth infection and 10.2% had malaria parasitaemia. Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a reduction in HPV-16 or HPV-18 GMT at Month 7 or Month 12 follow-up visits among participants with helminths or malaria. There was some evidence that participants with malaria had increased GMTs compared to those without malaria. CONCLUSIONS: The data show high HPV immunogenicity regardless of the presence of malaria and helminth infections. The mechanism and significance for the increase in GMT in those with malaria is unknown

A Phase I Randomized Placebo Controlled Trial of the Safety of 3% SPL7013 Gel (VivaGel®) in Healthy Young Women Administered Twice Daily for 14 Days

To assess the safety of VivaGel® used vaginally twice daily for 14 days among healthy, sexually-abstinent women, aged 18-24 years in the USA and Kenya.Randomized placebo controlled trial.Participants were randomized 2∶1, VivaGel to placebo. Safety was assessed by comparing genitourinary (GU) adverse events (AEs), colposcopy findings, vaginal lactobacilli and laboratory abnormalities by arm.Fifty-four women were enrolled; 35 in the VivaGel arm and 19 in the placebo arm. Twenty-six (74%) and 10 (53%) women reported taking all doses of VivaGel and placebo, respectively. No grade 3 or 4 AEs, or serious AEs occurred. Twenty-five (71%) participants in the VivaGel arm compared to 10 (53%) participants in the placebo arm had at least one grade 1 or 2 GU AE associated with product use (RR = 1.4, 95% CI 0.8-2.2). All seven grade 2 GU AEs associated with product use occurred among four women in the VivaGel arm. Vulvar and cervical erythema, cervical lesions, symptomatic BV, urinary frequency and metrorrhagia were more common in the VivaGel arm than the placebo arm. Twenty-nine (83%) participants in the VivaGel arm had a colposcopic finding compared to 10 (53%) participants in the placebo arm (RR = 1.6, 95%CI = 1.0-2.5). Two women in the VivaGel arm prematurely discontinued product use themselves due to a reported GU AE. Persistence of H₂O₂-producing and non-producing lactobacilli did not differ by study arm.GU AEs and colposcopic findings consistent with mild epithelial irritation and inflammation occurred more commonly among women in the VivaGel arm.ClinicalTrials.gov NCT003311032

iSKID: From integrated pilot scale runs to GMP implementation approach

One of the most compelling business reasons for integrated processing is the ability to de-risk capital investment due to a significantly more productive process that takes less space and fewer campaigns to generate clinical and commercial material. Boehringer Ingelheim and Pfizer developed the iSKID, a fully integrated and automated system that hydraulically links the perfusion bioreactor with several downstream unit operations (2xProtein A columns, continuous viral inactivation, AEX in flow through mode, and SPTFF). The Protein A elution cycles are discrete and separated by \u3e2hrs, allowing the ability to discard cycles that do not meet process specifications. The discreteness between product cycles and hydraulic linkage enables the sanitization between cycles for a robust bioburden control strategy. Each cycle is captured in a single use mixer (SUM), where the product is pooled in stable conditions until viral filtration, ultrafiltration/diafiltration and final filtration are performed in batch mode. Identical iSKID prototypes at 100L scale were used at three different sites to generate product quality, process, and bioburden data from three different molecules. The data has been used to understand implementation gaps in GMP facilities and process platforms (CMC1/CMC2). In addition, the team identified specific items to present to the FDA’s Emerging Technology Team (ETT). These items include our strategies for batch definition, microbial control, and process control. In this talk, we will use the data generated from the consistency runs to elaborate on the robustness of the process and touch upon the strategies to be presented to the ETT

Development of a pharmacovigilance safety monitoring tool for the rollout of single low-dose primaquine and artemether-lumefantrine to treat Plasmodium falciparum infections in Swaziland: a pilot study.

BACKGROUND Countries remain reluctant to adopt the 2012 World Health Organization recommendation for single low-dose (0.25 mg/kg) primaquine (SLD PQ) for Plasmodium falciparum transmission-blocking due to concerns over drug-related haemolysis risk, especially among glucose-6-phosphate dehydrogenase-deficient (G6PDd) people, without evidence demonstrating that it can be safely deployed in their settings. Pharmacovigilance methods provide a systematic way of collecting safety data and supporting the rollout of SLD PQ. METHODS The Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT), comprising: (1) a standardized form to support the surveillance of possible adverse events following SLD PQ treatment; (2) a patient information card to enhance awareness of known adverse drug reactions of SLD PQ use; and (3) a database compiling recorded information, was developed and piloted. Data on patient characteristics, malaria diagnosis and treatment are collected. Blood samples are taken to measure haemoglobin (Hb) and test for G6PD deficiency. Active follow-up includes a repeat Hb measurement and adverse event monitoring on or near day 7. A 13-month prospective pilot study in two hospital facilities in Swaziland alongside the introduction of SLD PQ generated preliminary evidence on the feasibility and acceptability of PROMPT. RESULTS PROMPT was well received by nurses as a simple, pragmatic approach to active surveillance of SLD PQ safety data. Of the 102 patients enrolled and administered SLD PQ, none were G6PDd. 93 (91.2 %) returned on or near day 7 for follow-up. Four (4.6 %) patients had falls in Hb ≥25 % from baseline, none of whom presented with signs or symptoms of anaemia. No patient's Hb fell below 7 g/dL and none required a blood transfusion. Of the 11 (11 %) patients who reported an adverse event over the study period, three were considered serious and included two deaths and one hospitalization; none were causally related to SLD PQ. Four non-serious adverse events were considered definitely, probably, or possibly related to SLD PQ. CONCLUSION Improved pharmacovigilance to monitor and promote the safety of the WHO recommendation is needed. The successful application of PROMPT demonstrates its potential as an important tool to rapidly generate locally acquired safety data and support pharmacovigilance in resource-limited settings

Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria : An Open-Label, Phase 1, Dose-Adjustment Trial

Erratum: The Journal of Infectious Diseases, Volume 217, Issue 7, 1 April 2018, Page 1171, https://doi.org/10.1093/infdis/jiy074Methods: We conducted an open-label, nonrandomized, dose-adjustment trial of the safety of 3 single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys aged 11–17 years and those aged 5–10 years, including G6PD-normal control groups. The primary outcome was the greatest within-person percentage drop in hemoglobin concentration within 10 days after treatment. Results: Fifty-one participants were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or 0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There was no evidence of symptomatic hemolysis, and adverse events considered related to study drug (n = 4) were mild. The mean largest within-person percentage change in hemoglobin level between days 0 and 10 was −9.7% (95% confidence interval [CI], −13.5% to −5.90%) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ, −11.5% (95% CI, −16.1% to −6.96%) in G6PD-deficient boys aged 11–17 years, and −9.61% (95% CI, −7.59% to −13.9%) in G6PD-deficient boys aged 5–10 years. The lowest hemoglobin concentration at any point during the study was 92 g/L. Conclusion: SLD-PQ doses between 0.40 and 0.50 mg/kg were well tolerated in G6PD-deficient males in Mali.Methods: We conducted an open-label, nonrandomized, dose-adjustment trial of the safety of 3 single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys aged 11–17 years and those aged 5–10 years, including G6PD-normal control groups. The primary outcome was the greatest within-person percentage drop in hemoglobin concentration within 10 days after treatment. Results: Fifty-one participants were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or 0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There was no evidence of symptomatic hemolysis, and adverse events considered related to study drug (n = 4) were mild. The mean largest within-person percentage change in hemoglobin level between days 0 and 10 was −9.7% (95% confidence interval [CI], −13.5% to −5.90%) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ, −11.5% (95% CI, −16.1% to −6.96%) in G6PD-deficient boys aged 11–17 years, and −9.61% (95% CI, −7.59% to −13.9%) in G6PD-deficient boys aged 5–10 years. The lowest hemoglobin concentration at any point during the study was 92 g/L. Conclusion: SLD-PQ doses between 0.40 and 0.50 mg/kg were well tolerated in G6PD-deficient males in Mali.Peer reviewe