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Mixed presentations, defined by simultaneous occurrence of depressive and manic symptoms, are difficult to treat. Antidepressants, although commonly used, have weak evidence of efficacy and may increase risk of mood destabilization. The aim of this pooled post hoc analysis was to evaluate the efficacy of cariprazine in the treatment of bipolar depression with or without concurrent manic symptoms.
Patients from 3 randomized, double-blind, placebo-controlled studies who met DSM-IV-TR or DSM-5 criteria for bipolar I disorder with a current major depressive episode were identified to have concurrent manic symptoms by baseline Young Mania Rating Scale total score ≥4. Efficacy was assessed in cariprazine 1.5 and 3 mg/day dose groups versus placebo; analyses included the least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score.
Of 1383 patients randomized to treatment, 808 (58.4%) had concurrent manic symptoms. For patients with manic symptoms, mean reduction in MADRS total score from baseline to week 6 was significantly greater for both cariprazine 1.5 and 3 mg/day compared with placebo, with least squares mean differences (LSMDs) versus placebo of −2.5 (p = .0033) and −2.9 (p = .0010), respectively; for patients without manic symptoms, the LSMD was significant for 1.5 mg/day (−3.3; p = .0008), but not for 3 mg/day (−1.9; p = .0562).
The results of this post hoc analysis suggest that cariprazine may be an appropriate treatment option for patients with bipolar I depression with or without manic symptoms, with higher doses potentially more effective in patients with manic symptoms.
Second-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions.
After reading this article you will be able to:
•understand the relative incidence of cardiotoxic side-effects of the various SGAs
•perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs
•understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients.
The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
Declaration of interest
F.G. has received honoraria for advisory work and lectures or CME activity support from Roche, BMS, Lundbeck, Otsuka, Janssen and Sunovion, is a collaborator on an NHS Innovations project co-funded by Janssen and has a family member with professional links to Lilly and GSK, including shares. R.M.M. has received honoraria for lectures from Lundbeck, Otsuka, Janssen and Sunovian. M.D.F. has received honoraria for lectures from Janssen and Sunovian. Z.A. has received honoraria for advisory work and lectures from Roche, Sanofi, Lilly and Otsuka. O.H. has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Astra-Zeneca, Autifony, Biogen, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. D.T. has received funding for lectures and research from Janssen, Otsuka, Servier, Lundbeck, Sunovion.
In preparation for a multisite antibiotic stewardship intervention, we assessed knowledge and attitudes toward management of asymptomatic bacteriuria (ASB) plus teamwork and safety climate among providers, nurses, and clinical nurse assistants (CNAs).
Prospective surveys during January–June 2018.
All acute and long-term care units of 4 Veterans’ Affairs facilities.
The survey instrument included 2 previously tested subcomponents: the Kicking CAUTI survey (ASB knowledge and attitudes) and the Safety Attitudes Questionnaire (SAQ).
A total of 534 surveys were completed, with an overall response rate of 65%. Cognitive biases impacting management of ASB were identified. For example, providers presented with a case scenario of an asymptomatic patient with a positive urine culture were more likely to give antibiotics if the organism was resistant to antibiotics. Additionally, more than 80% of both nurses and CNAs indicated that foul smell is an appropriate indication for a urine culture. We found significant interprofessional differences in teamwork and safety climate (defined as attitudes about issues relevant to patient safety), with CNAs having highest scores and resident physicians having the lowest scores on self-reported perceptions of teamwork and safety climates (P < .001). Among providers, higher safety-climate scores were significantly associated with appropriate risk perceptions related to ASB, whereas social norms concerning ASB management were correlated with higher teamwork climate ratings.
Our survey revealed substantial misunderstanding regarding management of ASB among providers, nurses, and CNAs. Educating and empowering these professionals to discourage unnecessary urine culturing and inappropriate antibiotic use will be key components of antibiotic stewardship efforts.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Inappropriate antibiotic use is associated with increased antimicrobial resistance and adverse events that can lead to further downstream patient harm. Preventative strategies must be employed to improve antibiotic use while reducing avoidable harm. We use the term “antibiotic never events” to globally recognize and define the most inappropriate antibiotic use.
Background: Phantogeusia associated with Parkinson Disease has not heretofore been reported. Methods: A 59 year old right handed female presented with a four year history of a bitter, sour and sweet taste on her entire tongue and roof of her mouth, 8/10 intensity, constant, persistent, without any external stimuli. Drinking water tasted bitter and sour. The phantogeusia was unresponsive to dietary changes, gabapentine, and allergy medications. Results: Abnormalities in Neurological examination: Decreased blink frequency. Hypokinetic. Hypomimetic face. Mood appears sad. Cranial Nerve (CN) examination: CN lll, lV, Vl: Saccadization of horizontal eye movements. Motor Examination: Pill rolling tremor in right hand. 1+ cogwheel rigidity in left upper extremity. Gait: 2+ retropulsion. Chemosensory testing: Olfactory: Alcohol Sniff Test: 6 (anosmia). SNAP Phenylethyl Alcohol Threshold Testing left -2.5 (hyposmia) & right > -2.0 (anosmia). Gustatory testing: Propylthiouracil Disc Taste test: 10 (normogeusia). Taste Testing Threshold: normogeusia to NaCl, Sucrose, HCl, Urea, and PTC. Other: DOPAPET: positive for Parkinson disease. Upper endoscopy: normal. Conclusions: Investigation for the presence of parkinsonian features in those with phantogeusia is warranted and chemosensory dysfunction including phantogeusia in those who presents with Parkinson’s disease is worthy of exploration.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Blastoschizomyces capitatus is an uncommon opportunistic yeast associated with infections in neutropaenic patients secondary to haematological malignancies, with a special predilection for the lungs. Globalisation and population migration impact on the epidemiology of infection with this organism but its effect on the immunocompetent population has rarely been described. We present here a case report, an overview of 11 other cases published between 2000 and 2016, and a comprehensive literature review of Blastoschizomyces pneumonia in the non-immunocompromised. The median age at diagnosis was 68 years (range 40–86 years) and more than half the cases reported a positive history of either current or past tobacco smoking. Six cases had either clinical or radiological evidence of chronic obstructive pulmonary disease and three had a history of prior treated tuberculosis. Fluconazole and itraconazole, alone or in combination, was the most utilised treatment. We conclude that unlike most other invasive yeast species, B. capitatus poses an infectious risk for immunocompetent patients, usually of middle to older age with risk factors for distorted lung architecture. Further research is warranted into the pathophysiology of Blastoschizomyces infections in the immunocompetent, including standardised treatment options.
The present work consists of an investigation of the turbulence radiation interaction (TRI) in a radiative turbulent channel flow of grey gas bounded by isothermal hot and cold walls. The optical thickness
of the channel is varied from 0.1 to 10 to observe different regimes of TRI. A high-resolution finite volume method for radiative heat transfer is employed and coupled with the direct numerical simulation (DNS) of the flow. The resulting effects of TRI on temperature statistics are strongly dependent on the considered optical depth. In particular, the contrasting role of emission and absorption is highlighted. For a low optical thickness the effect of radiative fluctuations on temperature statistics is low and causes the reduction of temperature variance through the dissipating action of emission. On the other hand, while increasing optical thickness to relatively high levels, the dissipation of temperature variance is balanced, at low wavenumbers in the turbulence spectrum, through the preferential action of absorption, which increases the large-scale temperature fluctuations. A significant rise in the effect of radiation on the temperature variance can be observed as a consequence of the reduction of radiative heat transfer length scales.
The PALFA survey, the most sensitive blind search for radio pulsars, has now discovered 180 pulsars in the Galactic Plane, the vast of which have periods shorter than 2 seconds. One reason that pulsar surveys may miss long-period radio pulsars is the strong effect of red noise at low modulation frequencies. It is possible to address this reduction in sensitivity by using a Fast-Folding Algorithm (FFA). We have adapted this algorithm for radio pulsar searching and applied it to PALFA observations. A sensitivity analysis of the algorithm has been conducted using synthetic pulsar signals injected in real observational data and this study shows that the FFA improves the PALFA survey sensitivity, as reported in Lazarus et al.(2015), by at least a factor of two at periods of ~6 sec, implying that the PALFA survey should discover more long-period radio pulsars in the future.
Background: The KCNT1 gene encodes subunits of the Na+-activated K+ channel, widely expressed in the CNS. Mutations of this gene have been implicated in Malignant Migrating Partial Seizures of Infancy (MMPSI). This early-onset epileptic encephalopathy represents a challenge due to pharmacoresistance. The channel-specific mutation represents the potential for targeted pharmacotherapy. Quinidine is a partial antagonist of the KCNT1 encoded channel; patients with MMPSI have been reported to have responded to doses ranging 34.4/kg/d - 60mg/kg/d. We present a case of MMPSI with a KCNTI mutation (c.G1283A:p.R428Q) trialled on quinidine. Methods: Following ineffective trials of 6 anti-seizure medications, this patient was trialled on oral quinidine. This patient was titrated up to a dose of 52mg/kg/d. Twenty-four hour EEG monitoring prior to quinidine therapy, and at target dose were compared. Results: Prior to initiation of quinidine, this patient experienced 22 electrographic seizures over 24 hours. At target dose, this patient experienced greater than 70 seizures over 24 hours. Conclusions: Quinidine has previously been reported to be effective in patients with MMPSI with the same and different mutations. We report the second case of a patient with MMPSI and KCNT1 mutation R428Q with poor clinical response to quinidine.
Suicidal behaviour is an under-reported and hidden cause of death in most low- and middle-income countries (LMIC) due to lack of national systematic reporting for cause-specific mortality, high levels of stigma and religious or cultural sanctions. The lack of information on non-fatal suicidal behaviour (ideation, plans and attempts) in LMIC is a major barrier to design and implementation of prevention strategies. This study aims to determine the prevalence of non-fatal suicidal behaviour within community- and health facility-based populations in LMIC.
Twelve-month prevalence of suicidal ideation, plans and attempts were established through community samples (n = 6689) and primary care attendees (n = 6470) from districts in Ethiopia, Uganda, South Africa, India and Nepal using the Composite International Diagnostic Interview suicidality module. Participants were also screened for depression and alcohol use disorder.
We found that one out of ten persons (10.3%) presenting at primary care facilities reported suicidal ideation within the past year, and 1 out of 45 (2.2%) reported attempting suicide in the same period. The range of suicidal ideation was 3.5–11.1% in community samples and 5.0–14.8% in health facility samples. A higher proportion of facility attendees reported suicidal ideation than community residents (10.3 and 8.1%, respectively). Adults in the South African facilities were most likely to endorse suicidal ideation (14.8%), planning (9.5%) and attempts (7.4%). Risk profiles associated with suicidal behaviour (i.e. being female, younger age, current mental disorders and lower educational and economic status) were highly consistent across countries.
The high prevalence of suicidal ideation in primary care points towards important opportunities to implement suicide risk reduction initiatives. Evidence-supported strategies including screening and treatment of depression in primary care can be implemented through the World Health Organization's mental health Global Action Programme suicide prevention and depression treatment guidelines. Suicidal ideation and behaviours in the community sample will require detection strategies to identify at risks persons not presenting to health facilities.
Histopathological anomalies of inner-ear structures in individuals with Down syndrome have been well documented; however, few studies have examined the radiological features.
A retrospective study was conducted of temporal bone computed tomography images in 38 individuals (75 ears) with Down syndrome to evaluate the prevalence of inner-ear abnormalities and assess vestibular aqueduct widths.
Inner-ear anomalies were identified in 20 of the 38 individuals (52.6 per cent). Seven of the 75 temporal bones (9.3 per cent) were found to have higher than previously reported. A dilated internal auditory canal and vestibule were more common among the present study group, while prior studies have demonstrated internal auditory canal stenosis and decreased vestibule size.
Down syndrome patients exhibit a high prevalence of dysplastic inner-ear features that confer substantial risk of sensorineural hearing loss. Computed tomography is a useful screening aid to detect inner-ear abnormalities, particularly enlarged vestibular aqueducts, which cause preventable sensorineural hearing loss in this population.
A new approach is proposed to analyze Bremsstrahlung X-rays that are emitted from laser-produced plasmas (LPP) and are measured by a stack type spectrometer. This new method is based on a spectral tomographic reconstruction concept with the variational principle for optimization, without referring to the electron energy distribution of a plasma. This approach is applied to the analysis of some experimental data obtained at a few major laser facilities to demonstrate the applicability of the method. Slope temperatures of X-rays from LPP are determined with a two-temperature model, showing different spectral characteristics of X-rays depending on laser properties used in the experiments.
Compressive Sensing is an emerging technology for data compression and simultaneous data acquisition. This is an enabling technique for significant reduction in data bandwidth, and transmission power and hence, can greatly benefit space-flight instruments. We apply this process to detect exoplanets via gravitational microlensing. We experiment with various impact parameters that describe microlensing curves to determine the effectiveness and uncertainty caused by Compressive Sensing. Finally, we describe implications for space-flight missions.
Proton therapy enables normal tissue sparing for curative-intent treatment of children with cancer who require radiation therapy. In the USA and elsewhere, proton therapy is being rapidly adopted, and many new proton centres are being established. Without a proton centre in Canada, children and their families must travel abroad for treatment at high cost and has raised the question whether a Canadian proton therapy facility is needed. METHODS: Canadian Pediatric Oncology centres were surveyed to assess current and future clinical practices. Needs were modeled by screening the Alberta Cancer Registry, ascertaining the number of children eligible for proton RT and comparing to the number who actually received this therapy. RESULTS: Most centres (63%) referred children, and 49 children were referred abroad between 2008 and 2013. Referrals were estimated to increase to 36 cases per annum across Canada. Most respondents (75%) supported that proton therapy will reduce late effects in most or selected cases compared to photon therapy. The registry search revealed 37,170 patients irradiated of which 379 children (1.0%) were potentially eligible for proton therapy, accounting for 15.9% of the new cases of childhood cancers diagnosed in Alberta over the interval. CONCLUSIONS: A strong perceived need for a pediatric proton therapy in Canada was identified. Proton therapy utilization was lower than modeled needs. Future referrals are anticipated to increase, with annual estimated cost of approximately $60 million spent outside of Canada that could be invested within the Canadian health care economy. These issues are worthy of further national discussion.