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To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust.
To investigate the impact of this temporary policy change on clinical and safety outcomes.
All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined.
Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02–28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection.
There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Co-occurrence of common mental disorders (CMD) with psychotic experiences is well-known. There is little research on the public mental health relevance of concurrent psychotic experiences for service use, suicidality, and poor physical health. We aim to: (1) describe the distribution of psychotic experiences co-occurring with a range of non-psychotic psychiatric disorders [CMD, depressive episode, anxiety disorder, probable post-traumatic stress disorder (PTSD), and personality dysfunction], and (2) examine associations of concurrent psychotic experiences with secondary mental healthcare use, psychological treatment use for CMD, lifetime suicide attempts, and poor self-rated health.
We linked a prospective cross-sectional community health survey with a mental healthcare provider database. For each non-psychotic psychiatric disorder, patients with concurrent psychotic experiences were compared to those without psychotic experiences on use of secondary mental healthcare, psychological treatment for CMD, suicide attempt, physical functioning, and a composite multimorbidity score, using logistic regression and Cox regressions.
In all disorders except for anxiety disorder, concurrent psychotic experiences were accompanied by a greater odds of all outcomes (odds ratios) for a unit change in composite multimorbidity score ranged between 2.21 [95% confidence interval (CI) 1.49–3.27] and 3.46 (95% CI 1.52–7.85). Hazard ratios for secondary mental health service use for non-psychotic disorders with concurrent psychotic experiences, ranged from 0.53 (95% CI 0.15–1.86) for anxiety disorders with psychotic experiences to 4.99 (95% CI 1.22–20.44) among those with PTSD with psychotic experiences.
Co-occurring psychotic experiences indicate greater public mental health burden, suggesting psychotic experiences could be a marker for future preventive strategies improving public mental health.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
Although psychotic experiences in people without diagnosed mental health problems are associated with mental health service use, few studies have assessed this prospectively or measured service use by real-world clinical data.
To describe and investigate the association between psychotic experiences and later mental health service use, and to assess the role of symptoms of common mental health disorders in this association.
We linked a representative survey of south-east London (SELCoH-1, n=1698) with health records from the local mental healthcare provider. Cox regression estimated the association of PEs with rate of mental health service use.
After adjustments, psychotic experiences were associated with a 1.75-fold increase in the rate of subsequent mental health service use (hazard ratio (HR) 1.75, 95% CI 1.03–2.97) compared with those without PEs. Participants with PEs experienced longer care episodes compared with those without.
Psychotic experiences in the general population are important predictors of public mental health need, aside from their relevance for psychoses. We found psychotic experiences to be associated with later mental health service use, after accounting for sociodemographic confounders and concurrent psychopathology.
Conservationists have adopted community-based conservation (CBC) strategies to support landscape conservation programmes in East Africa, and these projects often involve community development assistance in exchange for a commitment to dedicating a portion of community lands for conservation management. There is, however, a dearth of empirical evidence assessing the effectiveness of CBC conservation programmes. This paper uses sub-metre-resolution satellite imagery to measure land-use change on four Kenyan group ranches that had created CBCs. Each ranch underwent a common participatory planning process that established a land-use plan involving three management zones: conservation, livestock grazing and settlement/cultivation. Using a satellite image time series, we recorded threat-based development – anthropogenic modification of natural areas and the density of structures – for each ranch. We found that CBCs with tourism lodges were more effective at controlling development than the CBCs without a lodge, particularly in the conservation zones and, to a lesser degree, in the grazing zones. We conclude that our use of very-high-resolution satellite imagery offers conservationists a cost-effective, fast and replicable approach to measuring CBC land-use change and that CBC projects can lead to positive conservation results.
Greenhouse experiments were conducted to elucidate the effects of water stress on photosynthetic parameters of soybean [Glycine max (L.) Merr. ‘Hutton′] and velvetleaf (Abutilon theophrasti Medik. # ABUTH). Stomatal conductance of both species responded curvilinearly to reductions in leaf water potential. At leaf water potentials less negative than −2.5 MPa, stomatal conductance, net photosynthetic rate, and transpiration rate were greater in velvetleaf than in soybean. Soybean photosynthetic rate was linearly related to stomatal conductance. Velvetleaf photosynthetic rate increased linearly with stomatal conductances up to 1.5 cm s–1; however, no increase in photosynthetic rate was observed at stomatal conductances greater than 1.5 cm s–1, indicating nonstomatal limitations to photosynthesis. As water stress intensified, stomatal conductance, photosynthetic rate, and transpiration of velvetleaf declined more rapidly than in soybean.
In a 2-yr field study conducted on a Weswood silt loam soil (Fluventic Ustochrepts), interspecific competition between soybeans [Glycine max (L.) Merr. ‘Hutton′] and velvetleaf (Abutilon theophrasti Medik. # ABUTH) resulted in greater than 40 and 50% reductions in soybean and velvetleaf seed yield, respectively. Leaf area index, number of mainstem nodes, total number of leaves, and plant dry weight of monocultured and intercropped velvetleaf differed significantly as early as 4 weeks after emergence. Interspecific competition had litttle or no effect on soybean morphology before 8 weeks after emergence. Soil water extraction occurred to 1-m depths in a monoculture of velvetleaf (five plants/m2) in 1984 and 1985. Monocultured soybeans (32.5 plants/m2) extracted water from a 1.5-m or greater depth of the soil profile during the same years. Soil water extraction in the intercropped plots resembled that of the monocultured velvetleaf treatment until soybeans attained R6, when soil water was extracted to a 1.5-m depth. The potential for interspecific competition for water existed early in the season before late-season soybean root development. Relative water content and leaf water potential (Ψw1) did not differ (0.05) between monocultured and intercropped soybeans in 1984 or 1985. In 1985, Ψw1 differed between monocultured and intercropped velvetleaf during anthesis. Leaf water potential values in the youngest, fully expanded leaves were approximately 0.3 and 0.4 MPa lower during midmorning and midday hours, respectively, in intercropped and monocultured velvetleaf. Transpiration and stomatal conductance did not differ between monocultured and intercropped soybeans or velvetleaf at any time during 1984. Photosynthetic and transpiration rates, stomatal conductance, and Ψw1 were lower in intercropped than in monocultured velvetleaf during anthesis in 1985, suggesting interspecific competition for soil water. Soybean water relations were not affected in either year. The data suggest that soybean yield reductions in soybean-velvetleaf interspecific competition are attributable to resource limitations other than water in south-central Texas.
Variation in interference relationships have been shown for a number of crop-weed associations and may have an important effect on the implementation of decision support systems for weed management. Multiyear field experiments were conducted at eight locations to determine the stability of corn-foxtail interference relationships across years and locations. Two coefficients (I and A) of a rectangular hyperbola equation were estimated for each data set using nonlinear regression procedures. The I and A coefficients represent percent corn yield loss as foxtail density approaches zero and maximum percent corn yield loss, respectively. The coefficient I was stable across years at two locations and varied across years at four locations. Maximum yield loss (A) varied between years at one location. Both coefficients varied among locations. Although 3 to 4 foxtail plants m−-1 row was a conservative estimate of the single-year economic threshold (Tc) of foxtail density, variation in I and A resulted in a large variation in Tc. Therefore, the utility of using common coefficient estimates to predict future crop yield loss from foxtail interference between years or among locations within a region is limited.
Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013–2014 influenza season. Little is known about the epidemiology of severe influenza during this season.
A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes.
A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4–6.9], P=.006 and 50–64 years, 2.5 [1.3–4.9], P=.007; reference age 18–49 years), male sex (1.9 [1.1–3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9–37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2–1.4], P<.001).
Risk factors for death among US patients with severe influenza during the 2013–2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.
Infect. Control Hosp. Epidemiol. 2015;36(11):1251–1260