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Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast US.
Design, Setting, and Participants
Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020 and May 8, 2020 within one of 15 participating hospitals in 5 health systems across 5 states in the Southeast US.
Methods
The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast US.
Results
A total of 502 patients were included, and the majority (476/502, 95%) had clinically evaluable outcomes. Hospital mortality was 16% (76/476), while 35% (177/502) required ICU admission, and 18% (91/502) required mechanical ventilation. By both univariate and adjusted multivariate analysis, hospital mortality was independently associated with age (adjusted odds ratio [aOR] 2.03 for each decade increase, 95% CI 1.56-2.69), male sex (aOR 2.44, 95% CI: 1.34-4.59), and cardiovascular disease (aOR 2.16, 95% CI: 1.15-4.09). As with mortality, risk of severe disease was independently associated with age (aOR 1.17 for each decade increase, 95% CI: 1.00-1.37), male sex (aOR 2.34, 95% CI 1.54-3.60), and cardiovascular disease (aOR 1.77, 95% CI 1.09-2.85).
Conclusions
In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast US. In-hospital mortality risk doubled with each subsequent decade of life.
Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder.
Methods
We completed a 12-month randomized controlled trial of cognitive remediation and of long-acting injectable (LAI) risperidone with 60 patients with a recent first episode of schizophrenia. Cognitive remediation involved programs focused on basic cognitive processes as well as more complex, life-like situations. Healthy behavior training of equal treatment time was the comparison group for cognitive remediation, while oral risperidone was the comparator for LAI risperidone in a 2 × 2 design. All patients were provided supported employment/education to encourage return to work or school.
Results
Both antipsychotic medication adherence and cognitive remediation contributed to cognitive improvement. Cognitive remediation was superior to healthy behavior training in the LAI medication condition but not the oral medication condition. Cognitive remediation was also superior when medication adherence and protocol completion were covaried. Both LAI antipsychotic medication and cognitive remediation led to significantly greater improvement in work/school functioning. Effect sizes were larger than in most prior studies of first-episode patients. In addition, cognitive improvement was significantly correlated with work/school functional improvement.
Conclusions
These results indicate that consistent antipsychotic medication adherence and cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/education, cognitive remediation and LAI antipsychotic medication show separate significant impact on improving work/school functioning.
The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).
Methods:
This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.
Results:
In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).
Conclusion:
Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.
The authors offer their appreciation of the astute commentaries by Scott and Pilkonis and Niedtfeld, Paret, and Schmahl regarding their chapter on borderline personality disorder. Scott and Pilkonis address some very important big picture themes regarding the conceptualization, etiology, and treatment of BPD, and Niedtfeld et al. more specifically comment on innovative research highlighting the interplay of neuroscience and psychotherapy. In this rejoinder, the authors comment on these and other issues and suggest that a developmental psychopathology framework for theory and research has promise for illuminating the nature and etiology of BPD and highlighting important directions for prevention and treatment.
Characterized by a combination of interpersonal, emotional, behavioral, and cognitive instability, borderline personality disorder (BPD) is a serious and often misunderstood condition. The prevalence of BPD is approximately 1.4 to 6%, with substantially higher estimates among psychiatric outpatients and inpatients. Beyond the personal costs of BPD in terms of suffering, BPD is strongly associated with functional impairment and high societal costs for mental healthcare. Clinical descriptions of BPD first appeared before the mid-twentieth century and have evolved to the present conceptualization of an overarching BPD construct represented by the key domains of emotion dysregulation, impulsivity, and interpersonal disturbance. BPD has a varying course, with many individuals achieving remission or recovery, but emotional and interpersonal vulnerabilities and functional impairments often persist for many years, even after structured treatment. The success of treatment for BPD over the past few decades, however, has countered common clinical lore that BPD patients are recalcitrant. Further, novel developments in research on the putative core vulnerabilities underlying BPD, as well as evidence that these vulnerabilities can be addressed in treatment, illuminate important future directions and hope for patients and loved ones affected by this disorder.
Introduction: Despite recent advances in resuscitation, some patients remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Vector change defibrillation (VC) and double sequential external defibrillation (DSED) have been proposed as alternate therapeutic strategies for OHCA patients with refractory VF. The primary objective was to determine the feasibility, safety and sample size required for a future cluster randomized controlled trial (RCT) with crossover comparing VC or DSED to standard defibrillation for patients experiencing refractory VF. Secondary objectives were to evaluate the intervention effect on VF termination and return of spontaneous circulation (ROSC). Methods: We conducted a pilot cluster RCT with crossover in four Canadian paramedic services and included all treated adult OHCA patients who presented in VF and received a minimum of three defibrillation attempts. In addition to standard cardiac arrest care, each EMS service was randomly assigned to provide continued standard defibrillation (control), VC or DSED. Services crossed over to an alternate defibrillation strategy after six months. Prior to the launch of the trial, 2,500 paramedics received in-person training for VC and DSED defibrillation using a combination of didactic, video and simulated scenarios. Results: Between March 2018 and September 2019, 152 patients were enrolled. Monthly enrollment varied from 1.4 to 6.1 cases per service. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no reported cases of defibrillator malfunction, skin burns, difficulty with pad placement or concerns expressed by paramedics, patients, families, or ED staff about the trial. In the standard defibrillation group, 66.6% of cases resulted in VF termination, compared to 82.0% in VC and 76.3% of cases in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusion: Findings from our pilot RCT suggest the DOSE VF protocol is feasible and safe. VF termination and ROSC were higher with VC and DSED compared to standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact patient-centered, clinical outcomes
Although there is some evidence that duration of untreated psychosis (DUP) is geographically stable, few have examined whether the phenomenon is temporally stable. We examined DUP in two cohorts within two discrete time periods (1995–1999 and 2003–2005) spanning a decade in the same geographically defined community psychiatric service with no early intervention programme. Patients were diagnosed by Structured Clinical Interview for DSM (SCID) and we determined the DUP using the Beiser Scale. The DUP of the 240 participants did not differ significantly between study periods.
Negative symptoms have been previously reported during the psychosis prodrome, however our understanding of their relationship with treatment-phase negative symptoms remains unclear.
Objectives:
We report the prevalence of psychosis prodrome onset negative symptoms (PONS) and ascertain whether these predict negative symptoms at first presentation for treatment.
Methods:
Presence of expressivity or experiential negative symptom domains was established at first presentation for treatment using the Scale for Assessment of Negative Symptoms (SANS) in 373 individuals with a first episode psychosis. PONS were established using the Beiser Scale. The relationship between PONS and negative symptoms at first presentation was ascertained and regression analyses determined the relationship independent of confounding.
Results:
PONS prevalence was 50.3% in the schizophrenia spectrum group (n = 155) and 31.2% in the non-schizophrenia spectrum group (n = 218). In the schizophrenia spectrum group, PONS had a significant unadjusted (χ2 = 10.41, P < 0.001) and adjusted (OR = 2.40, 95% CI = 1.11–5.22, P = 0.027) association with first presentation experiential symptoms, however this relationship was not evident in the non-schizophrenia spectrum group. PONS did not predict expressivity symptoms in either diagnostic group.
Conclusion:
PONS are common in schizophrenia spectrum diagnoses, and predict experiential symptoms at first presentation. Further prospective research is needed to examine whether negative symptoms commence during the psychosis prodrome.
We present a detailed analysis of the radio galaxy PKS
$2250{-}351$
, a giant of 1.2 Mpc projected size, its host galaxy, and its environment. We use radio data from the Murchison Widefield Array, the upgraded Giant Metre-wavelength Radio Telescope, the Australian Square Kilometre Array Pathfinder, and the Australia Telescope Compact Array to model the jet power and age. Optical and IR data come from the Galaxy And Mass Assembly (GAMA) survey and provide information on the host galaxy and environment. GAMA spectroscopy confirms that PKS
$2250{-}351$
lies at
$z=0.2115$
in the irregular, and likely unrelaxed, cluster Abell 3936. We find its host is a massive, ‘red and dead’ elliptical galaxy with negligible star formation but with a highly obscured active galactic nucleus dominating the mid-IR emission. Assuming it lies on the local M–
$\sigma$
relation, it has an Eddington accretion rate of
$\lambda_{\rm EDD}\sim 0.014$
. We find that the lobe-derived jet power (a time-averaged measure) is an order of magnitude greater than the hotspot-derived jet power (an instantaneous measure). We propose that over the lifetime of the observed radio emission (
${\sim} 300\,$
Myr), the accretion has switched from an inefficient advection-dominated mode to a thin disc efficient mode, consistent with the decrease in jet power. We also suggest that the asymmetric radio morphology is due to its environment, with the host of PKS
$2250{-}351$
lying to the west of the densest concentration of galaxies in Abell 3936.
When breast-feeding is not possible, commercially made human milk substitute is recommended. Some consumers would prefer to make their own homemade infant formula (HIF) and may seek information on this practice from internet sources. The purpose of the current study was to investigate the content of blogs posting HIF recipes.
Design:
Blog postings were identified through a comprehensive search conducted using the Google search engine and the following search terms along with the term ‘blog’: ‘Make Your Own Baby Formula’, ‘Homemade Baby Formula’, ‘Do It Yourself (DIY) Baby Formula’, ‘DIY Baby Formula’, ‘Baby Formula Recipe’ and ‘All Natural Baby Formula’. A quantitative content analysis of blogs offering recipes for HIF was completed. Blogs that met the inclusion criteria were reviewed for disclaimers, blogger’s credentials, rationale for HIF use, advertisement or sale of recipe ingredients and recipe ingredients.
Setting:
Worldwide Web.
Results:
Fifty-nine blogs, featuring one hundred forty-four recipes, met inclusion criteria. Among reviewed blogs, 33·9 % did not provide a disclaimer stating breast milk is the preferred option, 25·4 % recommended consulting a healthcare professional before using, and 76·3 % and 20·3 % either advertised or sold ingredients or recipe kits, respectively. Credentials of bloggers varied and only seven bloggers identified themselves as ‘nutritionists’. The three most frequently mentioned recipe ingredients were whole raw cow’s milk (24·3 %), raw goat’s milk (23·6 %) and liver (14·5 %).
Conclusions:
Clinicians should be aware of this trend, discuss source of formula with parents, advocate for appropriate infant feeding practices and monitor for side effects.
Psychological interventions that are brief, acceptable, effective and can be delivered by non-specialists are especially necessary in low- and middle-income countries, where mental health systems are unable to address the high level of psychosocial needs. Problem Management Plus (PM+) is a five-session intervention designed for those impaired by psychological distress while living in communities affected by adversity. Individual PM+ has demonstrated effectiveness in reducing distress in Kenya and Pakistan, and a group version of PM+ (Group PM+) was effective for conflict-affected women in Pakistan. This paper describes a feasibility and acceptability trial of locally adapted Group PM+ for women and men in an earthquake-affected region of rural Nepal.
Methods
In this feasibility cluster randomised controlled trial, participants in the experimental arm were offered five sessions of Group PM+ and participants in the control arm received enhanced usual care (EUC), which entailed brief psycho-education and providing referral options to primary care services with health workers trained in the mental health Gap Action Programme Intervention Guide (mhGAP-IG). A mixed-methods design was used to assess the feasibility and acceptability of Group PM+. Feasibility was assessed with criteria including fidelity and retention of participants. Acceptability was assessed through in-depth interviews with participants, family members, programme staff and other stakeholders. The primary clinical outcome was depression symptoms assessed using the Patient Health Questionnaire (PHQ-9) administered at baseline and 8–8.5 weeks post-baseline (i.e. after completion of Group PM+ or EUC).
Results
We recruited 121 participants (83% women and 17% men), with equal allocation to the Group PM+ and EUC arms (1:1). Group PM+ was delivered over five 2.5–3 hour sessions by trained and supervised gender-matched local non-specialists, with an average attendance of four out of five sessions. The quantitative and qualitative results demonstrated feasibility and acceptability for non-specialists to deliver Group PM+. Though the study was not powered to assess for effectiveness, for all five key outcome measures, including the primary clinical outcome, the estimated mean improvement was larger in the Group PM+ arm than the EUC arm.
Conclusion
The intervention and trial procedures were acceptable to participants, family members, and programme staff. The communities and participants found the intervention to be beneficial. Because feasibility and acceptability were established in this trial, a fully powered randomised controlled trial will be conducted for larger scale implementation to determine the effectiveness of the intervention in Nepal.
Associations between childhood abuse and various psychotic illnesses in adulthood are commonly reported. We aim to examine associations between several reported childhood adverse events (sexual abuse, physical abuse, emotional abuse, neglect and interpersonal loss) among adults with diagnosed psychotic disorders and clinical and psychosocial outcomes.
Methods
Within a large epidemiological study, the 2010 Australian National Survey of Psychosis (Survey of High Impact Psychosis, SHIP), we used logistic regression to model childhood adverse events (any and specific types) on 18 clinical and psychosocial outcomes.
Results
Eighty percent of SHIP participants (1466/1825) reported experiencing adverse events in childhood (sexual abuse, other types of abuse and interpersonal loss). Participants reporting any form of childhood adversity had higher odds for 12/18 outcomes we examined. Significant associations were observed with all psychosocial outcomes (social dysfunction, victimisation, offending and homelessness within the previous 12 months, and definite psychosocial stressor within 12 months of illness onset), with the strongest association for homelessness (odds ratio (OR) = 2.82). Common across all adverse event types was an association with lifetime depression, anxiety and a definite psychosocial stressor within 12 months of illness onset. When adverse event types were non-hierarchically coded, sexual abuse was associated with 11/18 outcomes, other types of abuse 13/18 and, interpersonal loss occurring in the absence of other forms of abuse was associated with fewer of the clinical and psychosocial outcomes, 4/18. When adverse events types were coded hierarchically (to isolate the effect of interpersonal loss in the absence of abuse), interpersonal loss was associated with lower odds of self-reproach (OR = 0.70), negative syndrome (OR = 0.75) and victimisation (OR = 0.82).
Conclusions
Adverse childhood experiences among people with psychosis are common, as are subsequent psychosocial stressors. Mental health professionals should routinely enquire about all types of adversities in this group and provide effective service responses. Childhood abuse, including sexual abuse, may contribute to subsequent adversity, poor psychosocial functioning and complex needs among people with psychosis. Longitudinal research to better understand these relationships is needed, as are studies which evaluate the effectiveness of preventative interventions in high-risk groups.
To examine the contributions of two aspects of executive functioning (executive cognitive functions and behavioral control) to changes in diabetes management across emerging adulthood.
Methods:
Two hundred and forty-seven high school seniors with type 1 diabetes were assessed at baseline and followed up for 3 years. The baseline assessment battery included performance-based measures of executive cognitive functions, behavioral control, IQ estimate (IQ-est), and psychomotor speed; self-report of adherence to diabetes regimen; and glycated hemoglobin (HbA1c) assay kits as a reflection of glycemic control.
Results:
Linear and quadratic growth curve models were used to simultaneously examine baseline performance on four cognitive variables (executive cognitive functions, behavioral control, IQ, and psychomotor speed) as predictors of indices of diabetes management (HbA1c and adherence) across four time points. Additionally, general linear regressions examined relative contributions of each cognitive variable at individual time points. The results showed that higher behavioral control at baseline was related to lower (better) HbA1c levels across all four time points. In contrast, executive cognitive functions at baseline were related to HbA1c trajectories, accounting for increasingly more HbA1c variance over time with increasing transition to independence. IQ-est was not related to HbA1c levels or changes over time, but accounted instead for HbA1c variance at baseline (while teens were still living at home), above and beyond all other variables. Cognition was unrelated to adherence.
Conclusions:
Different aspects of cognition play a different role in diabetes management at different time points during emerging adulthood years.
On two occasions, in 1580–1 and 1587, the Worcestershire gentleman Ralph Sheldon of Beoley and Weston (1537–1613) undertook to attend services in his parish church. This article seeks to make sense of these occasions of ‘conformity’, in the context of the situation and choices facing Catholics in Protestant England. It argues that Ralph consciously rejected the Jesuit message about non-attendance at the state church, a view he never abandoned. Never described by his contemporaries as ‘papistically affected’, let alone as an ‘obstinate recusant’, his later reputation as such is mistaken. By exploring the evidence relating to these occasions of official conformity, it is possible to see how he managed the challenge of being a Catholic living within the law. He could be regarded, and treated, as an obedient subject. He might thus be viewed as a church papist. However, since occasional conformity must itself also suggest recusancy, a more nuanced understanding of his position requires a reconsideration of some of the evidence.
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.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
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).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
The flora of Mediterranean ecosystems contains families with species having fully and under-developed embryos in their seeds. After-ripening for physiological dormancy release and smoke influence germination in many species. We investigated how after-ripening and embryo growth interact with smoke to influence the temporal dynamics of seedling emergence among fire ephemerals. Seeds were placed in the field and under standardized (50% relative humidity, 30°C) laboratory conditions to test the effects of summer conditions on physiological dormancy loss. Germination was tested with water or smoke compounds (smoke water, KAR1) at a simulated autumn/winter temperature (18/7°C). The timing and amount of seedling emergence with smoke was observed for seeds exposed to near-natural conditions. During summer, physiological dormancy was broken in all species, enabling germination at autumn/winter but not summer temperatures; no embryo growth occurred in seeds with under-developed embryos. At the start of the wet season, seedling emergence from seeds with fully developed embryos occurred earlier than from seeds with under-developed embryos. In a non-consistent manner among our study species, smoke and smoke compounds influenced the rate of embryo growth and amount of germination. Effects of smoke were noticeable in terms of number of emergents in the first emergence season. Among ecologically similar species, we have shown (1) that both thermal and embryo traits exclude germination in the summer, (2) how embryo size influences the timing of seedling emergence in autumn–winter, and (3) a reduced requirement for smoke in the second emergence season after a fire with a shift to reliance on seasonal cues for emergence.