Mental health issues in fetal alcohol spectrum disorder.

BACKGROUND: High numbers of individuals with Fetal Alcohol Spectrum Disorders (FASD) have been described as having mental health problems. AIMS: This article summarizes research about mental health problems in FASD and considers related developmental and environmental issues. METHOD: A computer-based literature search was conducted in the databases Medline, PsycINFO, Google Scholar, Academic Search Complete, and Education Resources Information Centre for articles addressing the prevalence and types of mental health issues in individuals affected by FASD. RESULTS: High rates of mental disorders within the FASD and prenatal alcohol exposure (PAE) population were found to be consistently reported for both internalizing and externalizing disorders. Moreover, problems that emerge in childhood may reflect a convergence of genetic, environmental, and neurophysiological factors that persist into adulthood. CONCLUSIONS: Researchers are beginning to document the impacts of PAE on later mental health development. Further longitudinal study is needed to determine whether there is an increasing severity of mental health deficits and consequences with age, and whether any such changes reflect increasingly deteriorating environmental factors or brain-based factors. Additionally, research is needed to design interventions to better address the unique mental health needs of this population.

The Current Status of Outcomes-Based Contracting for Manufacturers and Payers: An AMCP Membership Survey.

BACKGROUND: As the United States health care system shifts from traditional volume-based payments to value-based payments, outcomes-based contracts (OBCs) are gaining popularity among payers and manufacturers as a mechanism for the shift toward value. Under this model, stakeholders hope to align drug payment and value to real-world performance metrics (e.g., biomarkers and health care resource utilization). OBJECTIVE: To understand the experiences, perceptions, and needs of payers and manufacturers related to OBCs. METHODS: The Academy of Managed Care Pharmacy (AMCP) and Xcenda conducted an online survey with AMCP payer and manufacturer members. Participants were asked a series of questions regarding their use of OBCs, barriers to implementation, and elements required in establishing successful OBCs. The importance and urgency of specific impediments to successful OBC implementation were also assessed. RESULTS: The survey was fielded May 12, 2017, to June 7, 2017, yielding 65 responses (35 payers/30 manufacturers). While a minority of payers/manufacturers had at least 1 OBC in place (20%/33%), a majority had interest in future OBC use (71%/63%). Among those with at least 1 OBC in place, 86%/80% of payers/manufacturers had renewed at least 1 OBC in the past 5 years. All payers and 60% of manufacturers with OBCs included compliance measures. Improvement in clinical outcomes was also common (71%/70%) (e.g., reaching set laboratory values goals), and 71%/60% included avoidance of unnecessary medical resource use (e.g., hospitalization and emergency department visit). The barrier most frequently identified by payers in implementing OBCs was evidence that OBCs reduced pharmacy spending (60%), while manufacturers identified the inability to obtain accurate data/outcome measures (73%) as a major limiting factor. Payers/manufacturers endorsed the use of easily measurable outcomes (91%/100%) as most important in establishing successful OBCs. Manufacturers, and to a lesser extent payers, indicated that regulations and legal issues need to be addressed to make progress in OBC implementation (e.g., safe harbor for preapproval health care economic information [77%/46%] and exemption of OBCs for best-price requirements [83%/51%]). The only exception was the clarification of regulations for discussing information outside of an FDA-approved label, in which both manufacturers and payers indicated a very strong need (100%) to be addressed. CONCLUSIONS: Surveyed AMCP members are interested in OBCs and recognize their alignment to societal health goals and health care affordability, although actual use of these contracts has been somewhat limited to date. Results from this survey indicate that there is potential for OBC use to increase as barriers and limitations are addressed. DISCLOSURES: This research was sponsored by the Academy of Managed Care Pharmacy and Xcenda. Duhig, Kaufman, and Hughes are employed by Xcenda. Saha is employed by the Academy of Managed Care Pharmacy. Smith has nothing disclose. Study concept and design were contributed by Duhig, Kaufman, Saha, and Hughes. Kaufman and Hughes collected the data, and data interpretation was performed by all the authors. The manuscript was written by Saha, Smith, and Duhig, along with Kaufman and Hughes.

Evaluating polycyclic aromatic hydrocarbons using a yeast bioassay.

Sixteen polycyclic aromatic hydrocarbons (PAHs) were evaluated for the ability to activate aryl hydrocarbon (Ah) receptor signaling in a yeast-based bioassay. Individual PAHs were classified as inactive or as weakly, moderately, or strongly active based on induction of human Ah receptor signaling. Indeno[1,2,3-cd]pyrene, chrysene, benzo[a]anthracene, benzo[a]pyrene, benzo[j]fluoranthene, and benzo[k]fluoranthene were the most potent activators of human Ah receptor signaling. Various mixtures of PAHs had additive or synergistic effects in the bioassay. Environmental samples from the New Orleans (Louisiana, USA) and Detroit (Michigan, USA) areas that were previously analyzed for PAH composition and quantity were tested in this bioassay. Weak but statistically significant relationships were found when the analytically measured levels of PAHs were correlated with sample dilutions that gave 25% effective concentration signaling levels in the Ah receptor assay. We conclude that this Ah receptor signaling assay may be useful for preliminary biomonitoring of samples for PAHs and other Ah receptor ligands.

Effect of pethidine administered during the first stage of labor on the acid-base status at birth.

OBJECTIVE: To evaluate the association between the use of pethidine during the first stage of labor and the presence, type and timing of acidosis in the newborn at birth. STUDY DESIGN: Secondary data analysis of a randomized controlled trial, which included term singleton pregnancies diagnosed with dystocia and requiring active management of labor. Women were randomized to receive either 100 mg of pethidine or placebo. Statistical analyses were performed using chi(2) or Fisher's exact tests for proportions and multiple linear regression for continuous outcomes. RESULTS: Three hundred and eighty-three pregnant women with a valid arterial blood cord sample were included in the final analysis. Lower pH and bicarbonate levels, as well as higher pCO(2) levels were found in the pethidide group. A higher incidence of acidosis was found in the pethidine group (pH<7.12 OR: 8.59 95% C.I. 3.29, 22.46). The highest frequency of acidosis was encountered when pethidine-delivery interval was 5 h. CONCLUSION: Pethidine use during the first stage of labor was associated with an increased risk of acidosis at birth.

Phospho-Akt overexpression in non-small cell lung cancer confers significant stage-independent survival disadvantage.

PURPOSE: Akt is a signal transduction protein that plays a central role in inhibiting apoptosis in a variety of cell types including human cancer cells. In cell lines derived from human non-small cell lung cancers (NSCLCs), Akt has been shown to confer chemoresistance by inhibition of apoptosis in response to different chemotherapeutic agents including platinum-based agents, which are often the first-line therapy for NSCLCs. Only 20% to 30% of patients with NSCLC treated with chemotherapy have clinical evidence of response. The purpose of this study is to determine whether or not overexpression of activated Akt [i.e., phosphorylated Akt (pAkt)] is correlated with survival. EXPERIMENTAL DESIGN: We studied tumors from 61 patients with NSCLC in three tissue microarrays. All patients were followed for a period of 10 years or until death. The arrays were studied immunohistochemically with antibodies against pAkt, p53, and Ki-67. RESULTS: There was a statistically significant difference in survival between the 14 patients with strong pAkt staining and the 47 patients with weak to absent pAkt staining both by log-rank (P = 0.0416) and Breslow analysis (P = 0.0446). Difference in survival time with respect to pAkt status was also statistically significant even after accounting for stage at diagnosis (P = 0.004). Neither p53 nor Ki-67 was a statistically significant prognostic factor. CONCLUSIONS: Overexpression of pAkt is an independent prognostic factor. Additional studies of human NSCLCs are warranted to drive the development of targeted tumor-specific antineoplastic therapies.

Mortality from lung and kidney disease in a cohort of North American industrial sand workers: an update.

BACKGROUND: A previously published cohort study of some 2670 employees of the North American sand industry, followed through 1994, provided strong evidence of a causal relationship between quartz exposure and death from both silicosis and lung cancer, after allowance for cigarette smoking and in the absence of known occupational carcinogens. Unexpectedly, a significant excess mortality from chronic non-malignant renal disease [observed 16; expected 7.6; standardized mortality ratio (SMR) 212] was also found, whereas deaths from renal cancer at this stage were close to expectation (observed 6; expected 5.2). OBJECTIVES: Our primary aim was to discover whether death from chronic renal disease was related to the estimated intensity of crystalline silica exposure. A further aim was to determine whether or not our previous estimates of lung cancer and silicosis risk were confirmed by mortality in the cohort 6 years later. METHODS: With help from the US National Death Index, surviving members of the cohort, with the exception of employees of a small plant in Canada, were traced through 2000. The cause of death was determined for all who had died, for comparison against National and State mortality rates. Nested case-referent analyses were then undertaken, as previously, of deaths from lung cancer and silicosis, plus end-stage renal disease and kidney cancer, in relation to quantitative re-estimates of quartz exposure. RESULTS: The total number of deaths through 1994 was 990; there were 231 additional deaths during the period 1995-2000. The SMRs were significantly higher in the later than the earlier period, mainly due to a relative increase in heart disease and external causes. The updated odds ratios for lung cancer and silicosis were almost identical to those published previously, with lung cancer risk again related to average silica concentration and cumulative exposure, but not to length of employment. In contrast, risks of neither end-stage renal disease nor renal cancer were related to cumulative exposure, although now based on 19 cases (SMR 239), and 10 cases (SMR 202), respectively, in fact, opposite trends were apparent for both diseases. However, because of the small numbers there was only limited power to assess the statistical significance of these trends or of any separate relationship with the duration or intensity of exposure. CONCLUSIONS: Our findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of other known carcinogens, but failed to find similar evidence to explain the excess mortality from either chronic renal disease or kidney cancer.