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The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
To determine trends and impact on outcomes of atrial fibrillation (AF) in patients with pre-existing major depressive disorder(MDD).
While post-AF MDD has been extensively studied, contemporary studies including temporal trends on impact of pre-AF MDD on AF and post-AF outcomes are lacking.
We used Nationwide Inpatient Sample (NIS) from Healthcare Cost and Utilization Project (HCUP) from 2002 to 2012. We identified AF and MDD as primary and secondary diagnosis respectively using validated International Classification of Diseases, 9th Revision, and Clinical Modification (ICD9CM) codes, and used Cochrane-Armitage trend test and multivariate regression to generate adjusted odds ratios (aOR).
We analyzed total of 3,887,827 AF hospital admissions from 2002 to 2012 of which 6.78% had MDD. Proportion of hospitalizations with MDD increased from 4.93% to 14.19% (P-trend < 0.001). Utilization of atrial cardioversion was lower in patients with MDD (34.37% vs. 40.52%, P < 0.001). In-hospital mortality was significantly lower in patients with MDD (aOR0.749; 95% CI 0.664–0.846; P < 0.001) but discharge to specialty care was higher (aOR 1.695; 95%CI 1.650–1.741; P < 0.001). In addition, median length of hospitalization (2.5 vs. 2.13 days; P < 0.001) and median cost of hospitalization (28,246 vs. 22,663; P < 0.001) was higher in hospitalizations with MDD.
Our study displayed an increasing proportion of patients with MDD admitted due to AF in the last decade with lower mortality but higher morbidity post-AF. In addition, there was significantly less utilization of atrial cardioversion in this population along with higher median length and cost of hospitalization. There is a need to explore the reasons behind this disparity in outcomes and atrial cardioversion utilization in order to improve post-AF outcomes in this vulnerable population.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
To determine temporal trends, invasive treatment utilization and impact on outcomes of pre-infarction drug abuse (DA) on acute myocardial infarction (AMI) in adults.
DA is important risk factor for AMI. However, temporal trends in drug abuse on AMI hospitalization outcomes in adults are lacking.
We used Nationwide Inpatient Sample (NIS) from Healthcare Cost and Utilization Project (HCUP) from 2002 to 2012. We identified AMI and DA as primary and secondary diagnosis respectively using validated International Classification of Diseases, 9th Revision, and Clinical Modification (ICD9CM) codes, and used the CochraneArmitage trend test and multivariate regression to generate adjusted odds ratios (aOR).
We analyzed total of 7,174,274 AMI hospital admissions from 2002 to 2012 of which 1.67% had DA. Proportion of hospitalizations with DA increased from 5.63% to 12.08% (P trend < 0.001). Utilization of coronary artery bypass grafting (CABG) was lower in patients with DA (7.83% vs. 9.18%, P < 0.001). In-hospital mortality was significantly lower in patients with DA (aOR 0.811; 95% CI 0.693–0.735; P < 0.001) but discharge to specialty care was higher (aOR 1.076; 95% CI 1.025–1.128; P < 0.001). The median cost of hospitalization (40,834 vs. 37,253; P < 0.001) was higher in hospitalizations with DA.
We demonstrate an increasing proportion of adults admitted with AMI have DA over the decade. However, DA has paradoxical association with mortality in adults. DA is associated with lower CABG utilization and higher discharge to specialty care, with a higher mean cost of hospitalization. The reasons for the paradoxical association of DA with mortality and worse morbidity outcomes need to be explored in greater detail.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
There are often substantial delays before diagnosis and initiation of treatment in people bipolar disorder. Increased delays are a source of considerable morbidity among affected individuals.
To investigate the factors associated with delays to diagnosis and treatment in people with bipolar disorder.
Retrospective cohort study using electronic health record data from the South London and Maudsley NHS Foundation Trust (SLaM) from 1364 adults diagnosed with bipolar disorder. The following predictor variables were analysed in a multivariable Cox regression analysis on diagnostic delay and treatment delay from first presentation to SLaM: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder.
The median diagnostic delay was 62 days (interquartile range: 17–243) and median treatment delay was 31 days (4–122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18–3.06) and treatment delay (4.40, 3.63–5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33–0.41) and substance misuse disorders (0.44, 0.31–0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.
Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder, particularly those with alcohol/substance misuse disorders. These findings highlight a need to better identify the symptoms of bipolar disorder and offer appropriate treatment sooner in order to facilitate improved clinical outcomes. This may include the development of specialist early intervention services.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
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.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
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.
There is variation regarding the use of surgery and interventional radiological techniques in the management of epistaxis. This review evaluates the effectiveness of surgical artery ligation compared to direct treatments (nasal packing, cautery), and that of embolisation compared to direct treatments and surgery.
A systematic review of the literature was performed using a standardised published methodology and custom database search strategy.
Thirty-seven studies were identified relating to surgery, and 34 articles relating to interventional radiology. For patients with refractory epistaxis, endoscopic sphenopalatine artery ligation had the most favourable adverse effect profile and success rate compared to other forms of surgical artery ligation. Endoscopic sphenopalatine artery ligation and embolisation had similar success rates (73–100 per cent and 75–92 per cent, respectively), although embolisation was associated with more serious adverse effects (risk of stroke, 1.1–1.5 per cent). No articles directly compared the two techniques.
Trials comparing endoscopic sphenopalatine artery ligation to embolisation are required to better evaluate the clinical and economic effects of intervention in epistaxis.
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.
Here we report on the material chemistry following crystallization in the presence of water vapor of chlorinated formamidinium lead-triiodide (NH2CH = NH2PbI3−xClx) perovskite films. We found in-situ exposure to water vapor reduces, or possibly eliminates, the retention of chlorine (Cl) inside NH2CH = NH2PbI3−xClx crystals. There is a strong tendency toward Cl volatility, which indicates the sensitivity of these materials for their integration into solar cells. The requisite for additional efforts focused on the mitigation of water vapor is reported. Based on the in situ results, hot casting (<100 °C) in dry conditions demonstrates improved film coverage and Cl retention with efficiencies reaching 12.07%.
We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.
The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.
From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.
The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.
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.
Physicians participate in the screening, routine medical supervision, and disqualification of student-athletes. In doing so, they should understand that eligibility/disqualification decisions inevitably have associated liability issues. It is the responsibility of physicians to take the lead role in the student-athlete medical assessment process to allow for optimum safety in sports programmes. The first duty of the physician is to protect the health and well-being of the student-athlete. However, because there is potential liability associated with the screening/disqualification process, physicians are wise to develop sound and reasonable strategies that are in strict compliance with the standard of care. This article focusses on cardiac screening and disqualification for participation in sports.