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Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.
This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.
Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.
Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.
Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.
Behaviour that challenges in people with intellectual disability is associated with higher healthcare, social care and societal costs. Although behavioural therapies are widely used, there is limited evidence regarding the cost and quality-adjusted life-years (QALYs).
We aimed to assess the incremental cost per QALY gained of therapist training in positive behaviour support (PBS) and treatment as usual (TAU) compared with TAU using data from a cluster randomised controlled trial (Clinical Trials.gov registration: NCT01680276).
We conducted a cost-utility analysis (cost per QALY gained) of 23 teams randomised to PBS or TAU, with a total of 246 participants followed up over 36 months. The primary analysis was from a healthcare cost perspective with a secondary analysis from a societal cost perspective.
Over 36 months the intervention resulted in an additional 0.175 QALYs (discounted and adjusted 95% CI −0.068 to 0.418). The total cost of training in and delivery of PBS is £1598 per participant plus an additional cost of healthcare of £399 (discounted and adjusted 95% CI −603 to 1724). From a healthcare cost perspective there is an 85% probability that the intervention is cost-effective compared with TAU at a £30 000 willingness to pay for a QALY threshold.
There was a high probability that training in PBS is cost-effective as the cost of training and delivery of PBS is balanced out by modest improvements in quality of life. However, staff training in PBS is not supported given we found no evidence for clinical effectiveness.
Residual herbicides are routinely applied to control troublesome weeds in pumpkin production. Fluridone and acetochlor, Groups 12 and 15 herbicides, respectively, provide broad-spectrum PRE weed control. Field research was conducted in Virginia and New Jersey to evaluate pumpkin tolerance and weed control to PRE herbicides. Treatments consisted of fomesafen at two rates, ethalfluralin, clomazone, halosulfuron, fluridone, S-metolachlor, acetochlor emulsifiable concentrate (EC), acetochlor microencapsulated (ME), and no herbicide. At one site, fluridone, acetochlor EC, acetochlor ME, and halosulfuron injured pumpkin 81%, 39%, 34%, and 35%, respectively, at 14 d after planting (DAP); crop injury at the second site was 40%, 8%, 19%, and 33%, respectively. Differences in injury between the two sites may have been due to the amount and timing of rainfall after herbicides were applied. Fluridone provided 91% control of ivyleaf morningglory and 100% control of common ragweed at 28 DAP. Acetochlor EC controlled redroot pigweed 100%. Pumpkin treated with S-metolachlor produced the most yield (10,764 fruits ha–1) despite broadcasting over the planted row; labeling requires a directed application to row-middles. A separate study specifically evaluated fluridone applied PRE at 42, 84, 126, 168, 252, 336, and 672 g ai ha–1. Fluridone resulted in pumpkin injury ≥95% when applied at rates of ≥168 g ai ha–1; significant yield loss was noted when the herbicide was applied at rates >42 g ai ha–1. We concluded that fluridone and acetochlor formulations are unacceptable candidates for pumpkin production.
Contra the consensus view of the Shi jing 詩經 (Classic of Odes) and Chu ci 楚辭 (Verses of Chu) as the products of two distinct literary cultures, one northern and one southern, this article argues on the basis of intertextual analysis that the Chu ci developed in direct response to the Shi jing. The foremost poem in the anthology, the “Li sao” 離騷 (Parting's Sorrow) emerges as a metadiscursive journey through various Shi jing archetypes, the goal of which is to authorize its hero to say farewell to his ruler and homeland—a possibility denied by Shi jing poetics. A final section explores the relationship between the oppositional poetics of the “Li sao” and the rest of the Chu ci. The article concludes with some reflections on the limitations of the north–south model for historians of early Chinese literature.
Staff training in positive behaviour support (PBS) is a widespread treatment approach for challenging behaviour in adults with intellectual disability.
To evaluate whether such training is clinically effective in reducing challenging behaviour during routine care (trial registration: NCT01680276).
We carried out a multicentre, cluster randomised controlled trial involving 23 community intellectual disability services in England, randomly allocated to manual-assisted staff training in PBS (n = 11) or treatment as usual (TAU, n = 12). Data were collected from 246 adult participants.
No treatment effects were found for the primary outcome (challenging behaviour over 12 months, adjusted mean difference = −2.14, 95% CI: −8.79, 4.51) or secondary outcomes.
Staff training in PBS, as applied in this study, did not reduce challenging behaviour. Further research should tackle implementation issues and endeavour to identify other interventions that can reduce challenging behaviour.
This study examined the association and directionality of effect between mental wellbeing and depressive symptoms in Australian adolescents. Data were collected on two occasions 21 months apart. At Time 1, 1,762 10- to 14-year-old adolescents from a range of socio-economic status areas participated. At Time 2 (T2), 1,575 participated again. On both occasions, the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS) and the Children's Depression Inventory 2 (CDI 2) were administered via online survey. Cross-lagged, longitudinal path analyses demonstrated a negative association between earlier symptoms of depression and later positive mental wellbeing, and that the reverse was also true, though weaker. The model accounted for 20% of the variance in males’ T2 CDI 2 depressive symptom scores (26% for females) and 21% of the variance in males’ T2 SWEMWBS mental wellbeing scores (23% for females). Depressive symptomatology and mental wellbeing were highly correlated, but symptoms of depression were more strongly associated with later mental wellbeing than vice versa. This has implications for educational psychologists, teachers, health professionals, and policy makers seeking to reduce depressive symptoms or promote mental wellbeing. Focusing solely on the promotion of mental wellbeing, without intervening to reduce symptoms of depression, may limit the potential outcomes that might be achieved.
Enlist™ cotton contains the aad-12 and pat genes that confer resistance to 2,4-D and glufosinate, respectively. Thirty-three field trials were conducted focused on Enlist cotton injury from glufosinate as affected by cotton growth stage, application rate, and single or sequential applications. Maximum injury from a single application of typical 1X (542 g ae ha-1) and 2X use rates was 3 and 13%, respectively, regardless of growth stage. Injury from sequential applications of 1X or 2X rates was equivalent to single applications. Similar injury was observed with four commercial formulations of glufosinate. Cotton yield was never affected by glufosinate. This research demonstrates Enlist™ cotton has robust resistance to glufosinate at rates at least twice the typical use rate when applied once or twice at growth stages ranging from 2 to 12 leaves.
Although high dose n-3 PUFA supplementation reduces exercise- and hyperpnoea-induced bronchoconstriction (EIB/HIB), there are concurrent issues with cost, compliance and gastrointestinal discomfort. It is thus pertinent to establish the efficacy of lower n-3 PUFA doses. Eight male adults with asthma and HIB and eight controls without asthma were randomly supplemented with two n-3 PUFA doses (6·2 g/d (3·7 g EPA and 2·5 g DHA) and 3·1 g/d (1·8 g EPA and 1·3 g DHA)) and a placebo, each for 21 d followed by 14 d washout. A eucapnic voluntary hyperpnoea (EVH) challenge was performed before and after treatments. Outcome measures remained unchanged in the control group. In the HIB group, the peak fall in forced expiratory volume in 1 s (FEV1) after EVH at day 0 (−1005 (sd 520) ml, −30 (sd 18) %) was unchanged after placebo. The peak fall in FEV1 was similarly reduced from day 0 to day 21 of 6·2 g/d n-3 PUFA (−1000 (sd 460) ml, −29 (sd 17) % v. −690 (sd 460) ml, −20 (sd 15) %) and 3·1 g/d n-3 PUFA (−970 (sd 480) ml, −28 (sd 18) % v. −700 (sd 420) ml, −21 (sd 15) %) (P<0·001). Baseline fraction of exhaled nitric oxide was reduced by 24 % (P=0·020) and 31 % (P=0·018) after 6·2 and 3·1 g/d n-3 PUFA, respectively. Peak increases in 9α, 11β PGF2 after EVH were reduced by 65 % (P=0·009) and 56 % (P=0·041) after 6·2 and 3·1 g/d n-3 PUFA, respectively. In conclusion, 3·1 g/d n-3 PUFA supplementation attenuated HIB and markers of airway inflammation to a similar extent as a higher dose. Lower doses of n-3 PUFA thus represent a potentially beneficial adjunct treatment for adults with asthma and EIB.
If we believe social media, newspapers, and even some of our best friends and colleagues, the war over standard usage is on. As with many wars, the opposing sides seem to be entrenched in differing ideological positions and many of the battles seem to take place over the most unstable, smallest bits of territory - such as the Oxford comma, singular they, or split infinitives. In this ongoing war, possessive apostrophes have attracted particularly aggressive forays. For example, when some English cities proposed removing apostrophes from street signs, various news outlets published headlines such as, ‘It's a catastrophe for the apostrophe in Britain’ (NBC, 31 January, 2009), ‘Dropped apostrophes spark grammar war in Britain’ (New York Times, 16 March, 2013), and ‘“It's pandering to the lowest common denominator”: Anger as Cambridge bans apostrophe from street names’ (Daily Mail, 18 January, 2014). Explaining Birmingham's ban, one city councillor was not that much less sensational, stating that apostrophes ‘denote possessions that are no longer accurate, and are not needed’ and that ‘they confuse people. If I want to go to a restaurant, I don't want to have an A-level (high school diploma) in English to find it’ (NBC).
We present simulation results from a version of the Regional Ocean Modeling System modified for ice shelf/ocean interaction, including the parameterisation of basal melting by molecular diffusion alone. Simulations investigate the differences in melting for an idealised ice shelf experiencing a range of cold to hot ocean cavity conditions. Both the pattern of melt and the location of maximum melt shift due to changes in the buoyancy-driven circulation, in a different way to previous studies. Tidal forcing increases both the circulation strength and melting, with the strongest impact on the cold cavity case. Our results highlight the importance of including a complete melt parameterisation and tidal forcing. In response to the 2.4°C ocean warming initially applied to a cold cavity ice shelf, we find that melting will increase by about an order of magnitude (24 × with tides and 41 × without tides).
Gut microbes have a substantial influence on systemic immune function and allergic sensitisation. Manipulation of the gut microbiome through prebiotics may provide a potential strategy to influence the immunopathology of asthma. This study investigated the effects of prebiotic Bimuno-galactooligosaccharide (B-GOS) supplementation on hyperpnoea-induced bronchoconstriction (HIB), a surrogate for exercise-induced bronchoconstriction, and airway inflammation. A total of ten adults with asthma and HIB and eight controls without asthma were randomised to receive 5·5 g/d of either B-GOS or placebo for 3 weeks separated by a 2-week washout period. The peak fall in forced expiratory volume in 1 s (FEV1) following eucapnic voluntary hyperpnoea (EVH) defined HIB severity. Markers of airway inflammation were measured at baseline and after EVH. Pulmonary function remained unchanged in the control group. In the HIB group, the peak post-EVH fall in FEV1 at day 0 (−880 (sd 480) ml) was unchanged after placebo, but was attenuated by 40 % (−940 (sd 460) v. −570 (sd 310) ml, P=0·004) after B-GOS. In the HIB group, B-GOS reduced baseline chemokine CC ligand 17 (399 (sd 140) v. 323 (sd 144) pg/ml, P=0·005) and TNF-α (2·68 (sd 0·98) v. 2·18 (sd 0·59) pg/ml, P=0·040) and abolished the EVH-induced 29 % increase in TNF-α. Baseline C-reactive protein was reduced following B-GOS in HIB (2·46 (sd 1·14) v. 1·44 (sd 0·41) mg/l, P=0·015) and control (2·16 (sd 1·02) v. 1·47 (sd 0·33) mg/l, P=0·050) groups. Chemokine CC ligand 11 and fraction of exhaled nitric oxide remained unchanged. B-GOS supplementation attenuated airway hyper-responsiveness with concomitant reductions in markers of airway inflammation associated with HIB.
Increased temporal and frontal slow-wave delta (1–4 Hz) and theta (4–7
Hz) activities are the most consistent resting-state neural abnormalities
reported in schizophrenia. The frontal lobe is associated with negative
symptoms and cognitive abilities such as attention, with negative
symptoms and impaired attention associated with poor functional
To establish whether frontal dysfunction, as indexed by slowing, would be
associated with functional impairments.
Eyes-closed magnetoencephalography data were collected in 41 participants
with schizophrenia and 37 healthy controls, and frequency-domain source
imaging localised delta and theta activity.
Elevated delta and theta activity in right frontal and right
temporoparietal regions was observed in the schizophrenia
v. control group. In schizophrenia, right-frontal
delta activity was uniquely associated with negative but not positive
symptoms. In the full sample, increased right-frontal delta activity
predicted poorer attention and functional capacity.
Our findings suggest that treatment-associated decreases in slow-wave
activity could be accompanied by improved functional outcome and thus
This article presents an overtly atheistic text from the early eighteenth century that has hitherto been completely unknown. It survives in manuscript in the Houghton Library at Harvard University, to which it was presented in 1841, and is claimed to be the work of the Scottish medical theorist, satirist, and poet, Archibald Pitcairne (1652–1713). Here, its links with Pitcairne and his milieu are assessed and its content evaluated, in conjunction with the provision of an annotated edition of the text itself.
Early findings from a national study of discharges from 32 National
Health Service medium secure units revealed that nearly twice as many
patients than expected were discharged back to prison.
To compare the characteristics of those discharged back to prison with
those discharged to the community, and consider the implications for
ongoing care and risk.
Prospective cohort follow-up design. All forensic patients discharged
from 32 medium secure units across England and Wales over a 12-month
period were identified. Those discharged to prison were compared with
those who were discharged to the community.
Nearly half of the individuals discharged to prison were diagnosed with a
serious mental illness and over a third with schizophrenia. They were a
higher risk, more likely to have a personality disorder, more symptomatic
and less motivated than those discharged to the community.
Findings suggest that alternative models of prison mental healthcare
should be considered to reduce risks to the patient and the public.