Nosocomial COVID-19 infection in the era of vaccination and antiviral therapy.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) vaccination and antiviral therapies have altered the course of the COVID-19 pandemic through mitigating severe illness and death. However, immunocompromised, elderly and multimorbid patients remain at risk of poor outcomes and are overrepresented in hospital populations. The aim of this study was to describe the characteristics and outcomes of patients with nosocomial COVID-19 infection. METHODS: This was a retrospective, observational study of patients who acquired COVID-19 after 7 days of hospital admission within the Southern Adelaide Local Health Network (SALHN) in South Australia between 1 June 2022 and 30 November 2022. Data were ascertained from the electronic medical record and the South Australian registry of births, deaths and marriages. RESULTS: Of 1084 COVID-19 inpatient cases managed in SALHN, 295 (27%) were nosocomial, with 215 included in the study. The median age of patients was 80 years (interquartile range [IQR], 68-88 years), the median Charlson Comorbidity Index score was 5 (IQR, 4-7) and 6% were immunocompromised. Most nosocomial COVID-19 infections were of mild severity (81%). The 30-day all-cause mortality rate following COVID-19 infection was 6%, and, in most cases, a cause of death other than COVID-19 was recorded on the death certificate. CONCLUSION: The majority of cases of nosocomial COVID-19 infection were mild, with a lower mortality rate than in earlier studies. This finding is likely attributable to immunity through vaccination and prior infection, early antiviral therapy and attenuated severity of the Omicron variant. The high proportion of nosocomial infections supports ongoing infection control measures.

'Looking after the survivors': the health of a cohort of long-term human immunodeficiency virus patients 25 years on.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection have higher rates of cardiovascular disease, metabolic disorders and malignancy than their uninfected peers. AIM: To survey the health of a South Australian cohort of long-term HIV patients, who had been diagnosed with HIV prior to the availability of combination antiretroviral therapy. METHODS: Data from 88 patients were collected retrospectively across four domains: demographics, HIV history, antiretroviral medication and medical comorbidity. RESULTS: There were high rates of cardiovascular risk factors, in particular active smoking, dyslipidaemia and diabetes mellitus, which translated into a high rate of ischaemic heart disease and cerebrovascular accidents. A large proportion of the patients suffered depression and cognitive impairment. Approximately one-fifth of the cohort had been diagnosed with a malignancy, with anal cancer being the most prevalent. Many patients had experienced permanent toxicity from antiretroviral therapy. CONCLUSION: The present study showed high rates of 'non-HIV morbidity' in a group of long-term HIV patients in South Australia. Clinicians should aggressively modify cardiovascular risk factors, ensure appropriate immunisations, monitor mental health and consider targeted malignancy screening in these patients. A robust clinical infrastructure and multidisciplinary team is required to facilitate the complex care needs of long-term HIV patients.

Are familial liability for schizophrenia and obstetric complications independently associated with risk of psychotic illness, after adjusting for other environmental stressors in childhood?

OBJECTIVE: The interplay between genetic and environmental factors on risk for psychotic illness remains poorly understood. The aim of this study was to estimate independent and combined effects of familial liability for schizophrenia and exposure to obstetric complications on risk for developing psychotic illness, covarying with exposure to other environmental stressors. METHODS: This whole-population birth cohort study used record linkage across Western Australian statewide data collections (midwives, psychiatric, hospital admissions, child protection, mortality) to identify liveborn offspring (n = 1046) born 1980-1995 to mothers with schizophrenia, comparing them to offspring of mothers with no recorded psychiatric history (n = 298,370). RESULTS: Both maternal schizophrenia and pregnancy complications were each significantly associated with psychotic illness in offspring, with no interaction. Non-obstetric environmental stressors significantly associated with psychotic illness in offspring included the following: being Indigenous; having a mother who was not in a partnered relationship; episodes of disrupted parenting due to hospitalisation of mother, father or child; abuse in childhood; and living in areas of greatest socioeconomic disadvantage and with elevated rates of violent crime. Adjustment for these other environmental stressors reduced the hazard ratio for maternal schizophrenia substantially (from hazard ratio: 5.7, confidence interval: 4.5-7.2 to hazard ratio: 3.5, confidence interval: 2.8-4.4), but not the estimate for pregnancy complications (hazard ratio: 1.1, confidence interval: 1.0-1.2). The population attributable fraction for maternal schizophrenia was 1.4 and for pregnancy complications was 2.1. CONCLUSION: Our finding of a substantial decrease in risk of psychotic illness associated with familial liability for psychosis following adjustment for other environmental stressors highlights potentially modifiable risk factors on the trajectory to psychotic illness and suggests that interventions that reduce or manage exposure to these risks may be protective, despite a genetic liability.

Risk of neurological, eye and ear disease in offspring to parents with schizophrenia or depression compared with offspring to healthy parents.

BACKGROUND: Neurological, visual and hearing deviations have been observed in the offspring of parents with schizophrenia. This study test whether children to parents hospitalized with schizophrenia have increased the likelihood of childhood neurological disorder. METHODS: Among all parents in Sweden born 1950-1985 and with offspring born 1968-2002: 7107 children with a parent hospitalized for schizophrenia were compared to 172 982 children with no parents hospitalized for schizophrenia or major depression, as well as to 32 494 children with a parent hospitalized for major depression as a control population with another severe psychiatric outcome. We estimated relative risks (RR) and two-sided 95% confidence intervals calculated from Poisson regression. RESULTS: Children to parents with schizophrenia were more likely than controls to have been hospitalized before the age of 10 with a diagnosis of cerebral palsy, RR = 1.76 (95% CI: 1.15-2.69); epilepsy, RR = 1.78 (95% CI: 1.33-2.40), combined neurological disease, RR = 1.33 (95% CI: 1.11-1.60) and certain diseases of the eye, RR = 1.92 (95% CI: 1.17-3.15) and ear, RR = 1.18 (95% CI: 1.05-1.32). Similar disease-risk-pattern was found for children to parents hospitalized with a diagnosis of major depression. A specific risk increase for strabismus RR = 1.21 (95%CI: 1.05-1.40) was found for off-spring with parental depression. CONCLUSIONS: Compared with children to healthy parents, children to parents with schizophrenia have increased risk of a variety of neurological disorders as well as visual and hearing disorders at an early age. The risk increase was not specific to schizophrenia but was also seen in children to parents with a diagnosis of major depression.

Candida spp. Deep Sternal Wound Infections: A Consequence of Antibiotic use?

A cluster of deep sternal wound infections caused by Candida spp. occurred at our institution. Investigation did not disclose a common environmental source. We postulate that broad-spectrum antibiotic surgical prophylaxis and liberal use of antibiotics contributed to these infections.

Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression.

BACKGROUND: Recent evidence points to partially shared genetics of neuropsychiatric disorders. AIMS: We examined risk of intellectual disability and other neuropsychiatric outcomes in 3174 children of mothers with schizophrenia, bipolar disorder or unipolar major depression compared with 3129 children of unaffected mothers. METHOD: We used record linkage across Western Australian population-based registers. The contribution of obstetric factors to risk of intellectual disability was assessed. RESULTS: Children were at significantly increased risk of intellectual disability with odds ratios (ORs) of 3.2 (95% CI 1.8-5.7), 3.1 (95% CI 1.9-4.9) and 2.9 (95% CI 1.8-4.7) in the maternal schizophrenia, bipolar disorder and unipolar depression groups respectively. Multivariate analysis suggests familial and obstetric factors may contribute independently to the risk. Although summated labour/delivery complications (OR = 1.4, 95% CI 1.0-2.0) just failed to reach significance, neonatal encephalopathy (OR = 7.7, 95% CI 3.0-20.2) and fetal distress (OR = 1.8, 95% CI 1.1-2.7) were independent significant predictors. Rates of rare syndromes in children of mothers with mental disorder were well above population rates. Risk of pervasive developmental disorders, including autism, was significantly elevated for children of mothers with bipolar disorder. Risk of epilepsy was doubled for children of mothers with unipolar depression. CONCLUSIONS: Our findings provide epidemiological support for clustering of neuropsychiatric disorders. Further larger epidemiological studies are warranted.

Management of pyogenic liver abscess: a South Australian experience.

BACKGROUND: There have been declining mortality rates associated with pyogenic liver abscess (PLA) in recent decades due to improvements in percutaneous drainage techniques, access to imaging and improvements in supportive care. The aim of this study was to analyse the aetiology, management and outcome of PLA at a tertiary hospital in Adelaide. METHODS: Data was collected retrospectively from 80 patients who were admitted with a PLA between 2011 and 2018. The data points covered demographic variables, presumed aetiology, microbiology results, abscess imaging characteristics, interventions, antibiotic treatment, complications and mortality. RESULTS: The majority of patients were Caucasian (86%) and the most common predisposing conditions were biliary tract disease (39%), intra-abdominal infection (20%) and diabetes (18%). Escherichia coli (21%), Klebsiella species (18%), Streptococcus anginosus group (14%) and anaerobes (18%) were the most frequent pathogens isolated. Fifty-one percent of patients were bacteraemic. Percutaneous catheter insertion (45%) was the most common form of drainage followed by percutaneous aspiration (13%), surgery (11%) and endoscopic retrograde cholangiopancreatography (6%), while 25% of patients did not undergo any form of drainage. Twenty-four patients (30%) suffered a complication with the highest proportion occurring in the medically managed group. The overall mortality rate was 9% with only 1% mortality rate attributable to PLA. CONCLUSION: This study demonstrates a continued preference for percutaneous drainage techniques over surgery in the management of PLA. A significant proportion of patients did not undergo abscess drainage and the risk of subsequent complications appeared to concentrate in this group, although the mortality rate from PLA was low.

Parsing components of risk of premature mortality in the children of mothers with severe mental illness.

INTRODUCTION: Children of mothers with severe mental illness are at increased risk of premature death including in infancy and early childhood. Importantly, these children are also more likely to be exposed to adverse socio-demographic risk factors and serious obstetric complications which, of themselves, may increase risk for childhood mortality. We examined mortality outcome at different ages up to 5 years taking account of these risks. METHOD: We used linked data across Western Australian whole-population psychiatric, inpatient, death, and midwives' registers to identify 15,486 births to mothers with severe mental illness and 452,459 births to mothers with no mental illness. Multivariable models were adjusted for exposure to adverse socio-demographic risk factors and serious obstetric complications. RESULTS: Overall risk of premature death was increased amongst children of mothers with severe mental illness (2.3%, 354 deaths) compared with children of mothers with no mental illness (1.4%, 6523 deaths); the same was true for specific risk of stillbirth, neonatal, post­neonatal and early childhood deaths. Risk was substantially attenuated after adjustment for adverse socio-demographic exposures, and further still after adjustment for exposure to serious obstetric complications. We observed no effects for the timing of maternal illness diagnosis. CONCLUSIONS: To minimise the risk of premature mortality in the children of mothers with severe mental illness, priority should be given to the prompt diagnosis of maternal mental illness with targeted delivery of high quality antenatal and psychiatric care, as well as social and structural supports for affected families that continue after birth.

Schizophrenia: from the brain to peripheral markers. A consensus paper of the WFSBP task force on biological markers.

Objective. The phenotypic complexity, together with the multifarious nature of the so-called "schizophrenic psychoses", limits our ability to form a simple and logical biologically based hypothesis for the disease group. Biological markers are defined as biochemical, physiological or anatomical traits that are specific to particular conditions. An important aim of biomarker discovery is the detection of disease correlates that can be used as diagnostic tools. Method. A selective review of the WFSBP Task Force on Biological Markers in schizophrenia is provided from the central nervous system to phenotypes, functional brain systems, chromosomal loci with potential genetic markers to the peripheral systems. Results. A number of biological measures have been proposed to be correlated with schizophrenia. At present, not a single biological trait in schizophrenia is available which achieves sufficient specificity, selectivity and is based on causal pathology and predictive validity to be recommended as diagnostic marker. Conclusions. With the emergence of new technologies and rigorous phenotypic subclassification the identification of genetic bases and assessment of dynamic disease related alterations will hopefully come to a new stage in the complex field of psychiatric research.

Intellectual Disability and Psychotic Disorders in Children: Association With Maternal Severe Mental Illness and Exposure to Obstetric Complications in a Whole-Population Cohort.

OBJECTIVE: Children of mothers with severe mental illness are at significantly increased risk of developing intellectual disability. Obstetric complications are also implicated in the risk for intellectual disability. Moreover, children of mothers with severe mental illness are more likely to be exposed to obstetric complications. The purpose of this study was to examine the independent and joint contributions of familial severe mental illness and obstetric complications to the risk of intellectual disability. METHOD: Record linkage across Western Australian whole-population psychiatric, inpatient, birth, and midwives' registers identified 15,351 children born between 1980 and 2001 to mothers with severe mental illness and 449,229 children born to mothers with no mental illness. Multivariable models were adjusted for paternal psychiatric status, parental intellectual disability, and other family and sociodemographic covariates. RESULTS: The risk of intellectual disability was increased among children of mothers with severe mental illness compared with children of unaffected mothers. The impact varied across maternal diagnostic groups. For children of mothers with schizophrenia, the unadjusted odds ratio was 3.8 (95% CI=3.0, 4.9) and remained significant after simultaneous adjustment for exposure to obstetric complications and other covariates (odds ratio=1.7, 95% CI=1.3, 2.3). The odds ratio for exposure to obstetric complications also remained significant after adjustment (odds ratio=1.7, 95% CI=1.6, 1.8). For intellectual disability of a genetic basis, the adjusted odds ratio for maternal schizophrenia was elevated but not statistically significant. Among children with intellectual disability, 4.2% later developed a psychotic disorder, compared with 1.1% of children without intellectual disability. CONCLUSIONS: Maternal severe mental illness and exposure to obstetric complications contribute separately to the risk of intellectual disability, suggesting potentially different causal pathways.

Neurobehavioral deficits in young adult offspring with heightened risk for psychosis who developed schizophrenia-spectrum disorder.

Neurobehavioral deficits in neuromotor function, verbal memory, executive function and attention found in patients with schizophrenia and their relatives have been suggested to be liability indicators or predictors of schizophrenia. It remains uncertain which of these neurobehavioral deficits are components of the illness itself or characteristics associated with genetic risk for it. The purpose of this study was to investigate the relation between these neurobehavioral deficits and schizophrenia-spectrum disorder in young adults at genetic risk for psychosis. A 93%-effective follow-up (total n=166, mean 22.4 yr of age) of a sample longitudinally investigated since fetal age provided complete data for mental disturbance, neuropsychological performance and neurological abnormality for 74 offspring at increased risk for psychosis (38 offspring of mothers with schizophrenia and 36 offspring of mothers with affective psychosis) and 88 normal-risk offspring. Abnormal glabella reflex and deficits in verbal memory, attention and complex executive functions seem specifically to be related to schizophrenia-spectrum disorder (primarily Cluster A personality disorders) among offspring at genetic risk for psychosis, while neurobehavioral deficits in general characterized offspring at heightened (vs. normal) genetic risk for psychosis, with no relation to schizophrenia-spectrum disorders. The two patterns of neurobehavioral deficits observed here may possibly reflect different causes and different aspects of a deviant neurodevelopmental process, and potentially contribute to a more nuanced version of this all-pervasive (but often non-specific) "model" of schizophrenia's development.

Barbara Fish and a Short History of the Neurodevelopmental Hypothesis of Schizophrenia.

The neurodevelopmental hypothesis of schizophrenia has become a paradigm broadly accepted in today's research in schizophrenia and its spectrum. This article traces the historical development of the neurodevelopmental hypothesis of schizophrenia up until the time of its explicit formulation in 1987, by Weinberger and by Murray and Lewis, with a main focus on the seminal contribution of Barbara Fish to its conception and elaboration.

A morphometric magnetic resonance method for measuring cranial, facial and brain characteristics for application to schizophrenia: part 1.

Serious psychopathology in adulthood may be associated with disturbed foetal brain development, which potentially shows lingering "fossil marks" in the cranial and facial regions. Several methods exist for assessing external craniofacial and internal brain distances but, to our knowledge, no method yet provides simultaneous measurement of cranial, facial and brain dimensions in live subjects. In this article we describe a method to identify landmarks on magnetic resonance images (MRI) for simultaneous measurement of cranial, facial and brain characteristics potentially associated with psychosis. To test the method itself, 30 patients with chronic schizophrenia and 31 healthy comparison subjects, mean age 41 years, were randomly selected from a larger cohort recruited at the Karolinska Hospital, Sweden. Participants were investigated with MRI, and 60 landmarks in the cranial, facial and brain regions were identified in the images. An independent anthropometric examination measured external craniofacial characteristics for study in relation to measurements produced through MRI. High inter-scorer and re-test reliabilities were obtained for two independent scorers of the landmarks in the MR images. Measurements of potentially comparable craniofacial distances showed high alignment with an established anthropometric method. This new method can provide simultaneous investigation of multiple aspects of cranial, facial and brain morphology in MR images originally collected for other purposes. In a second article we will use this method to compare 3D craniofacial measurements and shape between schizophrenia patients and healthy controls.

A pilot study of facial, cranial and brain MRI morphometry in men with schizophrenia: part 2.

This pilot study applies a new 3D morphometric MR method to test the hypothesis that men with schizophrenia (vs. controls) have deviant facial shapes and landmark relations in cranio/facial/brain (CFB) regions. This constitutes Part 2 of paired articles in this issue of Psychiatry Research: Neuroimaging, in which Part 1 presents the new method in detail. MRI coordinates from CFB landmarks of 23 patients and 15 controls were identified and then aligned with the Procrustes model, leaving shape as the only unit-less geometrical information. Men with schizophrenia had significantly longer mid- and lower-facial heights, and greater lower (left) facial depth, with a tendency toward rotation along the facial midline. This supports findings from earlier anthropometric and 3D studies of the "exterior" (face). In contrast, none of the patient-control differences for the new "interior" (cranial-brain) distances reached statistical significance. These results need to be retested on a larger sample of both sexes.

Neuropsychological impairment and its neurological correlates in adult offspring with heightened risk for schizophrenia and affective psychosis.

OBJECTIVE: Schizophrenia is generally considered to be a neurodevelopmental disorder reflected in findings of neuropsychological impairments and neurological abnormality in patients and their relatives. The authors investigated whether neuropsychological impairments are related to neurological abnormality and whether such deficits also characterize risk for affective psychosis. METHOD: In a longitudinal study with a 93% rate of effective follow-up, the authors investigated neuropsychological impairment and its relation to neurological abnormality at a mean age of 22.3 years in 74 offspring of mothers with a history of psychotic disorders (38 offspring with heightened risk for schizophrenia and 36 with risk for affective psychosis) and 88 normal-risk offspring born to mothers with no history of psychosis. RESULTS: Offspring with genetically heightened risk for schizophrenia showed significantly impaired verbal memory, selective attention, and grammatical reasoning, compared with normal-risk offspring. Having impaired verbal memory, attention, and grammatical reasoning functions identified a significantly larger subgroup (16%) among offspring with heightened risk for schizophrenia than among offspring with heightened risk for affective psychosis (0%) and among normal-risk offspring (3%). Multiple neuropsychological functions were significantly related to neurological abnormality in offspring with heightened risk for schizophrenia and in normal-risk offspring but not among offspring with heightened risk for affective psychosis. The extension of schizophrenia and affective psychosis risk groups to include additional offspring of mothers with psychosis-spectrum disorders yielded results similar to those for the core risk groups. CONCLUSIONS: The neurocognitive dysfunction attending heightened risk for schizophrenia is likely based on genetically mediated neurodevelopmental factors, with schizophrenia and affective psychosis belonging to different biological spheres.

Is craniofacial dysmorpholgy correlated with structural brain anomalies in schizophrenia?

This study aimed to examine the relationship between craniofacial dysmorphology and anomalies of brain morphology in schizophrenia. Assessments of craniofacial dysmorphology and magnetic resonance imaging of brain were performed independently of each other and blind to each other in 24 males with schizophrenia and 16 male controls. Ventricular cerebrospinal fluid volume was negatively correlated with total dysmorphology score in males with schizophrenia (i.e., the larger the ventricular cerebrospinal fluid volume, the lower the total dysmorphology score) but not in male controls. These findings suggest that craniofacial dysmorphology and anomalies of brain morphology may be associated with independent processes in the etiology of schizophrenia.

Prospective study of adult mental disturbance in offspring of women with psychosis.

BACKGROUND: The high-risk method is an important strategy for studying the antecedents and causes of schizophrenia and other psychoses. The Swedish High-Risk Project is a prospective longitudinal study of offspring of women with a history of schizophrenic, schizoaffective, affective, or unspecified functional psychoses and control women with no history of psychosis. The offspring and their environments were studied beginning before birth, and again during childhood. This article reports the mental outcome results from the first adult follow-up at age 22 years. METHODS: Of 178 offspring, 166 (93%) were followed up and blindly assessed using standardized methods, including a self-report scale for mental symptoms and the Structured Clinical Interview for DSM-III-R. RESULTS: Compared with controls (n = 91), the offspring of mothers with schizophrenia (n = 28) showed a significantly increased frequency of DSM-III-R Axis I and Axis II disorders, poor global functioning, high Symptom Checklist-90 scores, and a history of mental health care and psychopharmacologic medication use. Offspring of mothers with affective disorders (n = 22) showed high Symptom Checklist-90 scores, more frequent poor functioning, and receipt of mental health care, with a significant increase in Axis I depressive disorders and no increase in Axis II disorders. The extension of schizophrenia and affective risk groups to include additional maternal "spectrum cases" (10 and 15 individuals, respectively) generally yielded similar results. CONCLUSIONS: Maternal schizophrenia is associated with widespread increases in offspring mental disturbance in adolescence and young adulthood, differing from offspring disturbance associated with maternal affective disorder.

Prediction of adaptation difficulties by country of origin, cumulate psychosocial stressors and attitude toward integrating: a Swedish study of first-generation immigrants from Somalia, Vietnam and China.

BACKGROUND: Different types of accumulated stress have been found to have negative consequences for immigrants' capacity to adapt to the new environment. It remains unclear which factors have the greatest influence. AIMS: The study investigated whether immigrants' experience of great difficulty in adapting to a new country could best be explained by (1) country of origin, (2) exposure to accumulated stressors before arrival or (3) after arrival in the new country and/or (4) reserved attitude toward integrating into the new society. METHODS: The 119 first-generation immigrants from Somalia, Vietnam and China, living in Malmö, Sweden, were interviewed in a standardized manner. RESULTS: Experiencing great difficulty in adapting to Sweden was independent of length of residence, but significantly related to all four influences, studied one at a time. Country of origin was also related to stressors and attitude. When the effects of the other influences were mutually controlled for, only exposure to accumulated stressors in Sweden (and especially experiencing discrimination/xenophobia/racism) accounted for great adaptation difficulty. Stressors in Sweden had a greater effect if the immigrant had been exposed to stressors earlier. CONCLUSIONS: Immigrants' long-term experiences of great difficulty in adapting to a new country were explained primarily by exposure to accumulated stressors while moving to and living in the new country, rather than by their backgrounds or attitudes toward integrating. This suggests promoting strategies to avoid discrimination and other stressors in the host country.