Informatic Tools and Approaches in Postmarketing Pharmacovigilance Used by FDA

The safety profile of newly approved drugs and therapeutic biologics is less well developed by pre-marketing clinical testing than is the efficacy profile. The full safety profile of an approved product is established during years of clinical use. For nearly 40 years, the FDA has relied on the voluntary reporting of adverse events by healthcare practitioners and patients to help establish the safety of marketed products. Epidemiologic studies, including case series, secular trends, case-control and cohort studies, are used to supplement the investigation of a safety signal. Ideally, active surveillance systems would supplement the identification and exploration of safety signals. The FDA has implemented a number of initiatives to help identify safety problems with drugs and continues to evaluate their efforts

Reducing stroke risk in atrial fibrillation: Adherence to guidelines has improved, but patient persistence with anticoagulant therapy remains suboptimal.

Atrial fibrillation (AF) is a significant risk factor for avoidable stroke. Among high-risk patients with AF, stroke risk can be mitigated using oral anticoagulants (OACs), however reduction is largely contingent on physician prescription and patient persistence with OAC therapy. Over the past decade significant advances have occurred, with revisions to clinical practice guidelines relating to management of stroke risk in AF in several countries, and the introduction of non-vitamin K antagonist OACs (NOACs). This paper summarises the evolving body of research examining guideline-based clinician prescription over the past decade, and patient-level factors associated with OAC persistence. The review shows clinicians\u27 management over the past decade has increasingly reflected guideline recommendations, with an increasing proportion of high-risk patients receiving OACs, driven by an upswing in NOACs. However, a treatment gap remains, as 25–35% of high-risk patients still do not receive OAC treatment, with great variation between countries. Reduction in stroke risk directly relates to level of OAC prescription and therapy persistence. Persistence and adherence to OAC thromboprophylaxis remains an ongoing issue, with 2-year persistence as low as 50%, again with wide variation between countries and practice settings. Multiple patient-level factors contribute to poor persistence, in addition to concerns about bleeding. Considered review of individual patient\u27s factors and circumstances will assist clinicians to implement appropriate strategies to address poor persistence. This review highlights the interplay of both clinician\u27s awareness of guideline recommendations and understanding of individual patient-level factors which impact adherence and persistence, which are required to reduce the incidence of preventable stroke attributable to AF

Invasive Group A Streptococcal Infections, Clinical Manifestations and Their Predictors, Montreal, 1995–2002

Specific clinical manifestations of invasive group A streptococcal infection appear to develop not in response to the pathogen, but rather to host or environmental factors

Approach to device-detected subclinical atrial fibrillation

Subclinical atrial fibrillation, a commonly encountered entity in patients with implantable devices, has been associated with a number of adverse outcomes – the most important of which is thromboembolism. Through the detection of atrial high rate episodes, implanted devices offer a method to monitor for atrial fibrillation over extended periods of time. Several studies have demonstrated that patients with device-detected atrial tachyarrhythmias have an increased incidence of stroke, especially in the presence of additional risk factors. Yet, there are many uncertainties with limited evidence from randomised clinical studies and no formal guidelines to inform management in this population. This contributes to marked practice heterogeneity, underrecognition and missed opportunities for stroke prevention. We propose a logical approach to management of patients with device-detected atrial high rate episodes pending additional data from ongoing trials

Exploring H.pylori seropositivity as a risk factor for type 2 diabetes

Background: In the US, the percentage of adults with diagnosed diabetes are higher in members of racial and ethnic minority groups compared to non-Latino Whites. Understanding why such disparities exist has been less forthcoming. Methods: Secondary data analysis was conducted using the National Health and Nutrition Examination Survey (NHANES) 1999-2000 cross-sectional data. Results: H.pylori seropositivity was highest in Mexican Americans (43.7%), lowest in non-Hispanic Whites (18.1%). Diabetes was highest in non-Hispanic Blacks (5.9%); lowest in non-Hispanic whites (4.3%). H.pylori seropositivity was associated with greater likelihood of having type 2 diabetes (1.927, 95% CI 1.142, 3.257) compared to H.pylori negative in unadjusted model. After adjustment, H.pylori seropositivity was no longer associated with diabetes. Obesity (aOR 4.94, 95% CI 2.672,9.133) was associated with having type 2 diabetes compared to normal weight. Non-Hispanic Blacks (2.436, 95% CI 1.489,3.984) and Mexican Americans (1.896, 95% CI 1.002,3.587) had greater odds of diabetes compared to Whites. For nearly all stratified analyses, H.pylori did not have a significant association with type 2 diabetes although several other noteworthy findings emerged. A chance finding, where H.pylori was associated with greater likelihood of diabetes in Mexican Americans, 60-85, \u3e25 BMI, may be worth a closer look. Conclusion: Findings indicate weight status, obesity in particular, is the strongest predictor of diabetes followed by Black race. Stratified analyses suggest increasing racial disparities over the course of the life span

Delay in sexual maturation in perinatally HIV-infected youths is mediated by poor growth

OBJECTIVE: To evaluate the association between HIV infection and sexual maturation, and mediation of this association by HIV effects on growth. DESIGN: Pooled data were analyzed from two longitudinal cohort studies, the International Maternal Pediatric Adolescent AIDS Clinical Trials P219/219C Study (1993-2007) and the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (2007-2015), including perinatally HIV-infected (PHIV) and HIV-exposed uninfected (PHEU) youths. METHODS: We evaluated age at sexual maturity among 2539 PHIV and PHEU adolescents based on annual physician-assessed pubertal staging measures. Interval-censored regression models were used to evaluate associations of HIV infection with age at maturity. Mediation analyses accounting for height and BMI Z-scores at specific ages were used to estimate direct and indirect effects of HIV infection on age at sexual maturity. RESULTS: Mean ages at sexual maturity for PHIV girls (n = 1032) were 15.5 years for both female breast and pubic hair and 15.9 and 15.8 years for PHIV boys (n = 1054) for genitalia and pubic hair, respectively. PHIV youths matured approximately 6 months later on average than PHEU (n = 221 girls and 232 boys), and this difference persisted after adjustment for race/ethnicity and birth cohort. BMI and height Z-scores mediated the association between HIV infection and later maturation in girls, accounting for up to 74% of the total HIV effect. Only height Z-scores mediated the effect of HIV on male age at maturity, accounting for up to 98% of the HIV effect. CONCLUSION: PHIV youths attain sexual maturity later on average than PHEU youths. Much of this difference may be attributable to deficient growth, suggesting directions for future interventions

Is the incidence of congenital toxoplasmosis declining?

Prenatal infection with the protozoan parasite Toxoplasma gondii can cause congenital toxoplasmosis (CT), an often fatal or lifelong-disabling condition. Several studies of human populations have reported temporal decreases in seroprevalence, suggesting declining CT incidence. However, the consistency of this trend among diverse populations remains unclear, as does its implication for prenatal screening programmes, the major intervention against CT. Using temporally resolved data on the seroprevalence of T. gondii in various countries, we discuss how the parasite's changing epidemiology may affect trends in CT incidence in varying and counterintuitive ways. We argue that parasite stage-specific serology could be helpful for understanding underlying causes of secular changes in seroprevalence. Furthermore, we highlight the importance of updating cost-effectiveness estimates of screening programmes, accounting for neuropsychiatric sequelae

Evidence of suppression of onchocerciasis transmission in the Venezuelan Amazonian focus.

BACKGROUND: The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan®) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment. METHODS: Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme. RESULTS: From 2010 to 2012–2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012–2013 were, respectively, under 1 % and 20 L3/person/transmission season. Serology in children aged 1–10 years demonstrated that although 26 out of 396 (7 %) individuals still had Ov-16 antibodies, only 4/218 (2 %) seropositives were aged 1–5 years. CONCLUSIONS: We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75 % of the Yanomami population and 70 % of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1313-z) contains supplementary material, which is available to authorized users

Growing Up Toxic: Chemical Exposures and Increases in Developmental Disease

Explains how exposure to toxic chemicals can harm health and impair development, causing premature birth, learning disabilities, behavioral disorders, asthma and allergies, and/or other problems. Suggests policy reforms

Provider Opinion about Guidance Provided by a Prostate Cancer Screening Educational Pamphlet

cancer screening was addressed by providers in two Denver Veteran Affairs Medical Center (VAMC) primary care clinics testing a detailed prostate cancer screening educational pamphlet. Designing a prostate cancer screening educational pamphlet, educating primary care providers via email messages and measuring the providers’ perceptions of guidance provided by the pamphlet using an eight question survey were the means by which VAMC providers engaged in the type of shared decision making that practice guidelines recommend. The completed surveys indicated that the detailed pamphlet did offer providers guidance in explaining, considering, and engaging male veterans in deciding about prostate specific antigen testing. Providers in Firm B Clinic, the comparison group, did not routinely order PSAs because it is no longer a clinical reminder, but fear of liability often led to screening discussions. Despite the challenges, VAMC health care providers educated patients about the risks and benefits of screening before undergoing PSA testing. Public approval of the pamphlet that reflects current evidence based practice ensured that informed prostate cancer decision making was the standard of care within the VA Eastern Colorado Health Care System