Why patients sign out against medical advice (AMA): factors motivating patients to sign out AMA

A retrospective review of the against medical advice (AMA) discharges revealed that the majority of the patients left AMA for personal reasons, i.e., sickness or death in the family; reconciliation with spouse, girl friend, or family members; financial problems; and legal issues such as a court date. Strategies to reduce AMA discharges and increase patient retention in treatment are suggested.     

Selection and gene flow on a diminishing cline of melanic peppered moths

Historical datasets documenting changes to gene frequency clines are extremely rare but provide a powerful means of assessing the strength and relative roles of natural selection and gene flow. In 19th century Britain, blackening of the environment by the coal-fired manufacturing industry gave rise to a steep cline in the frequency of the black (carbonaria) morph of the peppered moth (Biston betularia) across northwest England and north Wales. The carbonaria morph has declined across the region following 1960s legislation to improve air quality, but the cline had not been comprehensively described since the early 1970s. We have quantified changes to the cline as of 2002, equivalent to an interval of 30 generations, and find that a cline still exists but that it is much shallower and shifted eastward. Joint estimation of the dominant fitness cost of carbonaria and dispersal parameters consistent with the observed cline change indicate that selection against carbonaria is very strong across the landscape (s approximately 0.2), and that dispersal is much greater than previously assumed. The high dispersal estimate is further supported by the weak pattern of genetic isolation by distance at microsatellite loci, and it implies that in addition to adult dispersal, wind-dispersed first instar larvae also contribute to lifetime dispersal. The historical perspective afforded by this study of cline reversal provides new insight into the factors contributing to gene frequency change in this species, and it serves to illustrate that, even under conditions of high dispersal and strong reverse selection acting against it, complete erosion of an established cline requires many generations.     

Measuring the news and its impact on democracy

Since the 2016 US presidential election, the deliberate spread of misinformation online, and on social media in particular, has generated extraordinary concern, in large part because of its potential effects on public opinion, political polarization, and ultimately democratic decision making. Recently, however, a handful of papers have argued that both the prevalence and consumption of “fake news” per se is extremely low compared with other types of news and news-relevant content. Although neither prevalence nor consumption is a direct measure of influence, this work suggests that proper understanding of misinformation and its effects requires a much broader view of the problem, encompassing biased and misleading—but not necessarily factually incorrect—information that is routinely produced or amplified by mainstream news organizations. In this paper, we propose an ambitious collective research agenda to measure the origins, nature, and prevalence of misinformation, broadly construed, as well as its impact on democracy. We also sketch out some illustrative examples of completed, ongoing, or planned research projects that contribute to this agenda.     

Effectiveness of proprotein convertase subtilisin/kexin‐9 monoclonal antibody treatment on plasma lipoprotein(a) concentrations in patients with elevated lipoprotein(a) attending a clinic

BackgroundLipoprotein(a) (Lp[a]) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin‐9 monoclonal antibodies (PCSK9mAbs) can lower Lp(a) levels in clinical trials, but their effects in patients with elevated Lp(a) in clinical practice remain unclear.AimsTo investigate the effectiveness and safety of PCSK9mAbs in lowering plasma Lp(a) in patients with elevated Lp(a) concentrations in a lipid clinic.MethodsThis was an open‐label study of 53 adult patients with elevated Lp(a) concentration (≥0.5 g/L). Clinical, biochemical, and safety data were collected before and on treatment with evolocumab or alirocumab over a mean period of 11 months.ResultsTreatment with a PCSK9mAb resulted in a significant reduction of 0.29 g/L (−22%) in plasma Lp(a) concentration (p<.001). There were also significant reductions in low‐density lipoprotein‐cholesterol (LDL‐C) (−53%), remnant‐cholesterol (−12%) and apolipoprotein B (−43%) concentrations. The change in Lp(a) concentration was significantly different from a comparable group of 35 patients with elevated Lp(a) who were not treated with a PCSK9mAb (−22% vs. −2%, p<.001). The reduction in Lp(a) concentration was not associated with the corresponding changes in LDL‐C, remnant‐cholesterol, and apolipoprotein B (p>.05 in all). 7.5% and 47% of the patients attained a target concentration of Lp(a) <0.5 g/L and LDL‐C <1.8 mmol/L, respectively. PCSK9mAbs were well tolerated, the common adverse effects being pharyngitis (9.4%), nasal congestion (7.6%), myalgia (9.4%), diarrhoea (7.6%), arthralgia (9.4%) and injection site reactions (11%).ConclusionPCSK9mAbs can effectively and safely lower plasma Lp(a) concentrations in patients with elevated Lp(a) in clinical practice; the impact of the fall in Lp(a) on ASCVD outcomes requires further investigation.     

The cost-effectiveness of HIV preventive measures among injecting drug users in Svetlogorsk, Belarus

AIM: To undertake a cost-effectiveness analysis of a harm reduction and HIV prevention project for injecting drug users (IDUs) in Eastern Europe. Economic evaluation methods were adapted to consider the effect of an 8-month financing gap that negatively impacted on project implementation. DESIGN: Financial and economic costs of implementing the intervention were analysed retrospectively. The data were also modelled to estimate the costs of a fully functioning project. Estimates of the intervention impact on sexual and drug injecting behaviour were obtained from existing pre- and post-intervention behavioural surveys of IDUs. A dynamic mathematical model was used to translate these changes into estimates of HIV infections averted among IDUs and their sexual partners. Projections of the potential effect of the shortfall in funding on the impact and cost-effectiveness of the intervention were made. SETTING: Svetlogorsk, Belarus, where in 1997 the IDU HIV prevalence was 74%. FINDINGS: The intervention averted 176 HIV infections (95% CI 60-270) with a cost-effectiveness of 359 dollars per HIV infection averted (95% CI 234-1054 dollars). Without the 2311 dollars reduction (7%) in financing, the estimated cost-effectiveness ratio of the project would have been 11% lower. The costing methods used to measure donated mass media can substantially influence cost and cost-effectiveness estimates. CONCLUSIONS: Harm reduction activities among IDUs can be cost-effective, even when IDU HIV prevalence and incidence is high. Relatively small shortfalls in funding reduce impact and cost-effectiveness. Increased and consistent allocation of resources to harm reduction projects could significantly reduce the pace of the HIV epidemic in Eastern Europe.     

Effects of 5-hydroxytryptamine uptake blockers on the concentration in brain of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in male rats, pro-oestrous rats and ovariectomized rats treated with oestrogen and progesterone

The aim of this study was to determine the effect of 5-hydroxytryptamine (5-HT) uptake blockade on 5-HT turnover by measuring the concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in brain with the aid of high performance liquid chromatography and electrochemical detection. The indoleamines were measured in the anterior hypothalamus (AH), posterior hypothalamus (PH) and raphe nuclei 30 min after the i.v. injection of either alaproclate (30 mg/kg) or zimelidine (20 mg/kg). The effect of alaproclate was studied in male rats, pro-oestrous female rats, rats ovariectomized and injected s.c. with 20 micrograms oestradiol benzoate (OB) on dioestrus and at 12.00 h of the next day (presumptive pro-oestrus) with 2 mg progesterone (model 1) and rats ovariectomized 3-4 weeks before an s.c. injection of 20 micrograms OB followed 72 h later by an s.c. injection of 2 mg progesterone (model 2). Alaproclate caused a significant decrease in the 5-HIAA/5-HT ratio in the AH and PH of the brain of male rats, in the PH and raphe nuclei in pro-oestrous rats and model 1, and in the raphe nuclei alone in model 2. Zimelidine had no effect on the 5-HIAA/5-HT ratio in any area in model 2. In male rats the injection of parachlorophenylalanine produced a marked reduction in the brain concentrations of 5-HT and 5-HIAA, but the 5-HIAA/5-HT ratio was unchanged by a subsequent injection of alaproclate. None of the pharmacological agents affected significantly the brain concentrations of noradrenaline, dopamine or dihydroxyphenylacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Steroid levels and steroid metabolism in relation to early gonadal development in the tilapia Oreochromis niloticus (Teleostei: cyprinoidei)

Sex steroid levels and steroid metabolism were investigated in relation to early gonadal development in a mixed sex population of the tilapia Oreochromis niloticus. Androstenedione (AD), testosterone (T), 11-ketotestosterone (KT), and estradiol (E2) were quantified by radioimmunoassay (RIA) of whole body extracts. Androstenedione metabolism was assessed by incubations in vitro with 3H-AD and metabolites were identified by thin-layer chromatography coupled with radioisotope image analysis. Histology revealed the presence of gonadal structures at 15 days postfertilization (dpf) and ovaries at 36 dpf, with other individuals exhibiting undifferentiated gonads containing germinal cells, presumably eventual testes. Androgen levels were initially high in eggs then decreased severalfold prior to the emergence of gonads. A transient increase in the levels of T and KT occurred at 22 dpf. Levels of E2 were either low or undetectable except for a transient increase (43 dpf) after ovaries were present. Levels of T approached bimodality from 57 to 64 dpf. Steroid metabolism generally increased throughout development. Metabolites were generally similar, consisting of T predominantly as well as 5beta-reduced androgen derivatives and 11-oyxgenated derivatives. Estriol was tentatively identified. Conjugated steroids were not formed. Two types of steroid metabolic profiles occurred at 50 dpf. These results demonstrate that changes in the steroidogenic profile occur during early transitions of gonadal development. Notably, (1) steroid biosynthetic capacity preceeds gonadal differentiation, (2) evidence for estrogens occurs after ovarian development has begun, and (3) bimodality of levels of T and differential steroid metabolism later in development may reflect the onset of sexual divergence.