A survey of internists’ recommendations for aspirin in older adults and barriers to evidence-based use

Journal of Thrombosis and Thrombolysis - Recent trials suggest that aspirin for primary prevention may do more harm than good for some, including adults over 70 years of age. We sought to...     

A systematic review of non‐surgical treatments for lentigo maligna

Lentigo maligna (LM) is the most common melanocytic malignancy of the head and neck. If left untreated, LM can progress to lentigo maligna melanoma (LMM). Complete surgical excision is the gold standard for treatment, however, due to the location, size, and advanced age of patients, surgery is not always acceptable. As a result, there is ongoing interest in alternative, less invasive treatment modalities. The objective was to provide a structured review of key literature reporting the use of radiotherapy, imiquimod and laser therapy for the management of LM in patients where surgical resection is prohibited. An independent review was conducted following a comprehensive search of the National Library of Medicine using MEDLINE and PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases. Data were presented in tabular format, and crude data pooled to calculate mean recurrence rates for each therapy. 29 studies met the inclusion criteria: radiotherapy 10; topical imiquimod 10; laser therapies 9. Radiotherapy demostrated recurrence rates of up to 31% (mean 11.5%), with follow‐up durations of 1–96 months. Topical imiquimod recurrence rates were up to 50% (mean 24.5%), with follow‐up durations of 2–49 months. Laser therapy yielded recurrence rates of up to 100% (mean 34.4%), and follow‐up durations of 8–78 months. in each of the treatment series the I² value measuring statistical heterogeneity exceeded the accepted threshold of 50% and as such a meta‐analysis of included data were inappropriate. For non‐surgical patients with LM, radiotherapy and topical imiquimod were efficacious treatments. Radiotherapy produced superior complete response rates and fewer recurrences than imiquimod although both are promising non‐invasive modalities. There was no consistent body of evidence regarding laser therapy although response rates of up to 100% were reported in low quality studies. A prospective comparative trial is indicated and would provide accurate data on the long‐term efficacy and overall utility of these treatments.     

Anogenital HIV RNA in Thai men who have sex with men in Bangkok during acute HIV infection and after randomization to standard vs. intensified antiretroviral regimens

Introduction

HIV transmission risk is highest during acute HIV infection (AHI). We evaluated HIV RNA in the anogenital compartment in men who have sex with men (MSM) during AHI and compared time to undetectable HIV RNA after three-drug versus five-drug antiretroviral therapy (ART) to understand risk for onward HIV transmission.

Methods

MSM with AHI (n=54) had blood, seminal plasma and anal lavage collected for HIV RNA at baseline, days 3 and 7, and weeks 2, 4, 12 and 24. Data were compared between AHI stages: 1 (fourth-generation antigen-antibody combo immunoassay [IA]–, third-generation IA–, n=15), 2 (fourth-generation IA+, third-generation IA–, n=9) and 3 (fourth-generation IA+, third-generation IA+, western blot–/indeterminate, n=30) by randomization to five-drug (tenofovir+emtricitabine+efavirenz+raltegravir+maraviroc, n=18) versus three-drug (tenofovir+emtricitabine+efavirenz, n=18) regimens.

Results

Mean age was 29 years and mean duration since HIV exposure was 15.4 days. Mean baseline HIV RNA was 5.5 in blood, 3.9 in seminal plasma and 2.6 log₁₀ copies/ml in anal lavage (p<0.001). Blood and seminal plasma HIV RNA were higher in AHI Stage 3 compared to Stage 1 (p<0.01). Median time from ART initiation to HIV RNA <50 copies/ml was 60 days in blood, 15 days in seminal plasma and three days in anal lavage. Compared with the three-drug ART, the five-drug ART had a shorter time to HIV RNA <1500 copies/ml in blood (15 vs. 29 days, p=0.005) and <50 copies/ml in seminal plasma (13 vs. 24 days, p=0.048).

Conclusions

Among MSM with AHI, HIV RNA was highest in blood, followed by seminal plasma and anal lavage. ART rapidly reduced HIV RNA in all compartments, with regimen intensified by raltegravir and maraviroc showing faster HIV RNA reductions in blood and seminal plasma.     

The demands of biochemical genetic disorders: a survey of mothers of children with mitochondrial disease or phenylketonuria

A telephone survey of mothers of children with mitochondrial disease (n = 29) or phenylketonuria (PKU) (n = 29) revealed that mothers of children with mitochondrial disease report greater stress and worry, less satisfaction with social supports, greater difficulty meeting their child's extra care needs, and more impact on multiple aspects of their personal lives. They also reported more missed days of work and used a greater number of health care services and personal resources. Interventions must be developed that address the demands of biochemical genetic disorders, particularly those with the uncertain trajectory of mitochondrial disease.     

Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles

Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during pathological overvaluations—price bubbles. The connection between the behavioral and neural underpinnings of such phenomena has been absent, in part due to a lack of enabling technology. We used a multisubject functional MRI paradigm to measure neural activity in human subjects participating in experimental asset markets in which endogenous price bubbles formed and crashed. Although many ideas exist about how and why such bubbles may form and how to identify them, our experiment provided a window on the connection between neural responses and behavioral acts (buying and selling) that created the bubbles. We show that aggregate neural activity in the nucleus accumbens (NAcc) tracks the price bubble and that NAcc activity aggregated within a market predicts future price changes and crashes. Furthermore, the lowest-earning subjects express a stronger tendency to buy as a function of measured NAcc activity. Conversely, we report a signal in the anterior insular cortex in the highest earners that precedes the impending price peak, is associated with a higher propensity to sell in high earners, and that may represent a neural early warning signal in these subjects. Such markets could be a model system to understand neural and behavior mechanisms in other settings where emergent group-level activity exhibits mistaken belief or valuation.Asset price bubbles are extended periods in which prices rise well above fundamental values. Identifying bubbles and predicting crashes from price data alone is a notoriously difficult problem (1). However, prices are created by the collective behavior of the market participants, so neural activity could offer biomarkers for the evolution of price bubbles. Studies of asset price bubbles indicate a role for psychological factors such as “euphoria” (2), “irrational exuberance” (3), “mania” (4), “animal spirits” (5), and “sentiment” (6). We sought neural data supporting such psychological constructs that might help to identify price bubbles.We observed the formation and crash of endogenous bubbles in experimental asset markets (7, 8) using multisubject neuroimaging. In each of 16 market sessions, consisting of an average of 20 traders (range, 11–23), we measured the neural activity of 2–3 participants (n = 44 total) using functional magnetic resonance imaging (fMRI). Our market design is based upon ref. 9. Traders could buy or sell one risky asset unit in each period. Fig. 1A illustrates the sequence of experimental events. Each market had 50 trading periods. All subjects began with 100 units of experimental currency (a risk-free asset) and 6 units of a risky asset. Each period, the risky asset paid a currency dividend d of either 0.40 or 1.00 per unit (with equal probability), creating an expected dividend E[d] = 0.70. Currency earned a fixed interest rate r of 5% each period. After all 50 rounds of trading were completed, the risky asset was redeemed for 14 units of the risk-free currency.Open in a separate windowFig. 1.Asset market experiment. (A) Each period subjects viewed the following screens, in order: Positions, Order Entry (×5), Trading Results, and Dividends and Interest. (B) Order elicitation procedure. Subjects responded Buy, Sell, or Hold to a random (uniform) price draw from each of five bins, each of width equal to 10% of the last period’s price. The middle bin was centered on the last period’s price. (C) How the price is chosen (=market clearing). The highest price at which subjects responded Buy, and the lowest price at which subjects responded Sell, were entered into a closed book call market. Prices and trading outcomes were reported on the Trading Results screen.These parameters defined an unambiguous fundamental value for the risky asset. Buying the risky asset in period t at price P_t and selling it one period later leads to the expected net gain E_t[P_t+1] ? P_t? + ?E[d]. The same investment of P_t in the risk-free asset yields a sure net gain of rP_t. If these two amounts are equal—in economic terms, if asset prices are “in equilibrium”—then there is a stationary price equal to a constant fundamental value F defined by F = E[d]/r = 0.70/0.05 = 14. Prices persistently above F = 14 indicate a bubble; such a clear bubble measure is rarely available in field data. Fig. 2A illustrates the price paths for all 16 markets in this experiment. Bubbles are typical and large: the median price peak was 64.30 (range, 19.68–156.01). The bubble paths always result in a crash, and prices in the final period are near the fundamental F = 14 (median, 14.13). Fig. 2B illustrates a typical experimental session. This market bubble crashed after period 30. Trading volume is substantial, which means that prices do not result from a few extreme traders.Open in a separate windowFig. 2.Endogenous market bubbles. (A) Price paths in16 different experimental market sessions. The dark line shows the average price in each period over the 16 sessions. Plotted below the prices is the normalized per-subject volume for each period; error bars are SEs. (B) Single-session prices (Top) and trading volume (Middle) from one statistically typical experimental session. At Bottom is shown the risky asset holdings; each subject is indicated by a different color. MRI subjects are shown with thicker lines. The dashed line is the “clairvoyant” profit-maximizing share path (assuming subjects could somehow correctly anticipate all future prices).