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.

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.

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.

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.

'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.

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.

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.

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.

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.

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.

Prospective study of pandysmaturation and adult mental disorder in high-risk and normal-risk offspring.

More than 50 years ago, Fish postulated that a special form of early abnormal neurodevelopment, "pandysmaturation", defined a priori as constituting retarded cranial development in the first year of life, combined with delay in early motor milestone attainment, was related to genetic risk for schizophrenia, and was associated with schizophrenia-spectrum disorders in young adulthood. Fish confirmed this in a very small sample. We retested Fish's postulation in a larger prospective study. Pandysmaturation was blindly investigated through medical records and prospective researcher and maternal observations, studying 75 "high-risk" offspring of women with a history of schizophrenia or affective psychosis and 91 "normal-risk" offspring. Subjects were studied prospectively from mother's pregnancy to 22 years of age, at which time the offspring were independently assessed for schizophrenia-spectrum and affective disorders. Pandysmaturation (n = 13, with 10 "definite" and 3 "probable" degrees) was significantly related to genetic risk for schizophrenia (Odds Ratio 4.9, p = 0.02) but not to genetic risk for affective disorders (OR 1.2, p = 0.81). Pandysmaturation was significantly associated with schizophrenia-spectrum (OR 6.2, p = 0.02), but not affective (OR 0.9, p = 0.90), disorders in young adulthood. Pandysmaturation was more strongly associated than was retarded cranial development, motor milestone delay, or social/cognitive milestone delay by itself. Pandysmaturation has efficacy as an early life risk-indicator of schizophrenia-spectrum disorder in young adulthood at least in subjects at genetic risk, strengthening the evidence for a generally genetic-based neurodevelopmental model of schizophrenia-spectrum (as contrasted with affective) disorders. Pandysmaturation is a risk-indicator for future schizophrenia-spectrum disorder, for potential use in scientific studies and clinical practice.

An exploratory model for G x E interaction on hippocampal volume in schizophrenia; obstetric complications and hypoxia-related genes.

BACKGROUND: Smaller hippocampal volume has repeatedly been reported in schizophrenia patients. Obstetric complications (OCs) and single nucleotide polymorphism (SNP) variation in schizophrenia susceptibility genes have independently been related to hippocampal volume. We investigated putative independent and interaction effects of severe hypoxia-related OCs and variation in four hypoxia-regulated schizophrenia susceptibility genes (BDNF, DTNBP1, GRM3 and NRG1) on hippocampal volume in schizophrenia patients and healthy controls. METHODS: Clinical assessment, structural MRI scans, and blood samples for genotyping of 32 SNPs were obtained from 54 schizophrenia patients and 53 control subjects. Information on obstetric complications was collected from original birth records. RESULTS: Severe OCs were related to hippocampal volume in both patients with schizophrenia and healthy control subjects. Of the 32 SNPs studied, effects of severe OCs on hippocampal volume were associated with allele variation in GRM3 rs13242038, but the interaction effect was not specific for schizophrenia. SNP variation in any of the four investigated genes alone did not significantly affect hippocampal volume. CONCLUSIONS: The findings suggest a gene-environment (G x E) interaction between GRM3 gene variants and severe obstetric complications on hippocampus volume, independent of a diagnosis of schizophrenia. Due to the modest sample size, the results must be considered preliminary and require replication in independent samples.

No effect of obstetric complications on basal ganglia volumes in schizophrenia.

BACKGROUND: Heterogeneous findings have been reported in studies of basal ganglia volumes in schizophrenia patients as compared to healthy controls. The basal ganglia contain dopamine receptors that are known to be involved in schizophrenia pathology and to be vulnerable to pre- and perinatal hypoxic insults. Altered volumes of other brain structures (e.g. hippocampus and lateral ventricles) have been reported in schizophrenia patients with a history of obstetric complications (OCs). This is the first study to explore if there is a relationship between OCs and basal ganglia volume in schizophrenia. METHODS: Thorough clinical investigation (including information on medication) of 54 schizophrenia patients and 54 healthy control subjects was undertaken. MR images were obtained on a 1.5T scanner, and volumes of nucleus caudatus, globus pallidum, putamen, and nucleus accumbens were quantified automatically. Information on OCs was blindly collected from original birth records. RESULTS: Unadjusted estimates demonstrated a relationship between increasing number of OCs and larger volume of nucleus accumbens in schizophrenia patients and healthy controls. No statistically significant relationships were found between OCs and the basal ganglia volumes when controlled for intracranial volume, age, and multiple comparisons. There were no effects of typical versus atypical medication on the basal ganglia volumes. The patients with schizophrenia had larger globus pallidum volumes as compared to healthy controls, but there were no case-control differences for accumbens, putamen, or caudate volumes. CONCLUSION: The present results do not support the hypothesis that OCs are related to alterations in basal ganglia volume in chronic schizophrenia.

Cerebral cortical thickness and a history of obstetric complications in schizophrenia.

INTRODUCTION: Magnetic resonance imaging (MRI) studies have demonstrated that patients with schizophrenia have thinner brain cortices compared with healthy control subjects. Neurodevelopment is vulnerable to obstetric complications (OCs) such as hypoxia and birth trauma, factors that are also related to increased risk of developing schizophrenia. With the hypothesis that OCs might explain the thinner cortices found in schizophrenia, we studied patients with schizophrenia and healthy controls subjects for association between number and severity of OCs and variation in cortical thickness. METHODS: MRI scans of 54 adults with schizophrenia or schizoaffective disorder and 54 healthy controls were acquired at Karolinska Institutet, Stockholm, Sweden. Measures of brain cortical thickness were obtained using automated computer processing (FreeSurfer). OCs were assessed from obstetric records and scored blindly according to the McNeil-Sjöström scale. At numerous cortical locations, putative effects of OCs on cortical thickness variation were tested for each trimester, for labour, for composite OC scores, severe OC scores, and hypoxia scores among patients and controls separately. RESULTS: Number and severity of OCs varied among both patient and control subjects but were not associated with cortical thickness in either of the groups. Patients demonstrated thinner brain cortices but there were no significant differences in number and severity of OC scores across groups. CONCLUSION: In the present study, number and severity of obstetric complications were not associated with brain cortical thickness, in patients with schizophrenia or in healthy control subjects. The thinner brain cortices found in patients with schizophrenia were not explained by a history of OCs.

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.