Swapnil Sharma

CONTEXT: A number of studies have found that the use of cannabis and other psychoactive substances is associated with an earlier onset of psychotic illness. OBJECTIVE: To establish the extent to which use of cannabis, alcohol, and other psychoactive substances affects the age at onset of psychosis by meta-analysis. DATA SOURCES: Peer-reviewed publications in English reporting age at onset of psychotic illness in substance-using and non-substance-using groups were located using searches of CINAHL, EMBASE, MEDLINE, PsycINFO, and ISI Web of Science. STUDY SELECTION: Studies in English comparing the age at onset of psychosis in cohorts of patients who use substances with age at onset of psychosis in non-substance-using patients. The searches yielded 443 articles, from which 83 studies met the inclusion criteria. DATA EXTRACTION: Information on study design, study population, and effect size were extracted independently by 2 of us. DATA SYNTHESIS: Meta-analysis found that the age at onset of psychosis for cannabis users was 2.70 years younger (standardized mean difference = -0.414) than for nonusers; for those with broadly defined substance use, the age at onset of psychosis was 2.00 years younger (standardized mean difference = -0.315) than for nonusers. Alcohol use was not associated with a significantly earlier age at onset of psychosis. Differences in the proportion of cannabis users in the substance-using group made a significant contribution to the heterogeneity in the effect sizes between studies, confirming an association between cannabis use and earlier mean age at onset of psychotic illness. CONCLUSIONS: The results of meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychotic illness, and they support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients. The results suggest the need for renewed warnings about the potentially harmful effects of cannabis.

BACKGROUND: The increased risk of suicide in the period after discharge from a psychiatric hospital is a well-recognized and serious problem. OBJECTIVE: The aim of this study was to establish the risk factors for suicide in the year after discharge from psychiatric hospitals and their usefulness in categorizing patients as high or low risk for suicide in the year following discharge. METHOD: A systematic meta-analysis of controlled studies of suicide within a year of discharge from psychiatric hospitals. RESULTS: There was a moderately strong association between both a history of self-harm (OR = 3.15) and depressive symptoms (OR = 2.70) and post-discharge suicide. Factors weakly associated with post-discharge suicide were reports of suicidal ideas (OR = 2.47), an unplanned discharge (OR = 2.44), recent social difficulty (OR = 2.23), a diagnosis of major depression (OR = 1.91) and male sex (OR = 1.58). Patients who had less contact with services after discharge were significantly less likely to commit suicide (OR = 0.69). High risk patients were more likely to commit suicide than other discharged patients, but the strength of this association was not much greater than the association with some individual risk factors (OR = 3.94, sensitivity = 0.40, specificity = 0.87). CONCLUSIONS: No factor, or combination of factors, was strongly associated with suicide in the year after discharge. About 3% of patients categorized as being at high risk can be expected to commit suicide in the year after discharge. However, about 60% of the patients who commit suicide are likely to be categorized as low risk. Risk categorization is of no value in attempts to decrease the numbers of patients who will commit suicide after discharge.

Context. One of the long-term goals of exoplanet science is the atmospheric characterization of dozens of small exoplanets in order to understand their diversity and search for habitable worlds and potential biosignatures. Achieving this goal requires a space mission of sufficient scale that can spatially separate the signals from exoplanets and their host stars and thus directly scrutinize the exoplanets and their atmospheres. Aims. We seek to quantify the exoplanet detection performance of a space-based mid-infrared (MIR) nulling interferometer that measures the thermal emission of exoplanets. We study the impact of various parameters and compare the performance with that of large single-aperture mission concepts that detect exoplanets in reflected light. Methods. We have developed an instrument simulator that considers all major astrophysical noise sources and coupled it with Monte Carlo simulations of a synthetic exoplanet population around main-sequence stars within 20 pc of the Sun. This allows us to quantify the number (and types) of exoplanets that our mission concept could detect. Considering single visits only, we discuss two different scenarios for distributing 2.5 yr of an initial search phase among the stellar targets. Different apertures sizes and wavelength ranges are investigated. Results. An interferometer consisting of four 2 m apertures working in the 4–18.5 μ.m wavelength range with a total instrument throughput of 5% could detect up to ≈550 exoplanets with radii between 0.5 and 6 R ⊕ with an integrated S / N ≥ 7. At least ≈160 of the detected exoplanets have radii ≤1.5 R ⊕ . Depending on the observing scenario, ≈25–45 rocky exoplanets (objects with radii between 0.5 and 1.5 R ⊕ ) orbiting within the empirical habitable zone (eHZ) of their host stars are among the detections. With four 3.5 m apertures, the total number of detections can increase to up to ≈770, including ≈60–80 rocky eHZ planets. With four times 1 m apertures, the maximum detection yield is ≈315 exoplanets, including ≤20 rocky eHZ planets. The vast majority of small, temperate exoplanets are detected around M dwarfs. The impact of changing the wavelength range to 3–20 μm or 6–17 μm on the detection yield is negligible. Conclusions. A large space-based MIR nulling interferometer will be able to directly detect hundreds of small, nearby exoplanets, tens of which would be habitable world candidates. This shows that such a mission can compete with large single-aperture reflected light missions. Further increasing the number of habitable world candidates, in particular around solar-type stars, appears possible via the implementation of a multi-visit strategy during the search phase. The high median S/N of most of the detected planets will allow for first estimates of their radii and effective temperatures and will help prioritize the targets for a second mission phase to obtain high-S/N thermal emission spectra, leveraging the superior diagnostic power of the MIR regime compared to shorter wavelengths.

BACKGROUND: Pain during pregnancy is common, and its management is complex. Certain analgesics may increase the risk for adverse fetal and pregnancy outcomes, while poorly managed pain can result in adverse maternal outcomes such as depression and hypertension. Guidelines to assist clinicians in assessing risks and benefits of exposure to analgesics for the mother and unborn infant are lacking, necessitating evidence-based recommendations for managing pain in pregnancy. METHODS: A comprehensive literature search was conducted to assess pregnancy safety data for pharmacological and nonpharmacological pain management methods. Relevant clinical trials and observational studies were identified using multiple medical databases, and included studies were evaluated for quality and possible biases. RESULTS: Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) are appropriate for mild to moderate pain, but NSAIDs should be avoided in the third trimester due to established risks. Short courses of weaker opioids are generally safe in pregnancy, although neonatal abstinence syndrome must be monitored following third trimester exposure. Limited safety data for pregabalin and gabapentin indicate that these are unlikely to be major teratogens, and tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors have limited but overall reassuring safety data. Many of the included studies were limited by methodological issues. CONCLUSIONS: Findings from this review can guide clinicians in their decision to prescribe analgesics for pregnant women. Treatment should be tailored to the lowest therapeutic dose and shortest possible duration, and management should involve a discussion of risks and benefits and monitoring for response. Further research is required to better understand the safety profile of various analgesics in pregnancy.