Incidence and associations of hospital delirium diagnoses in 85,979 people with severe mental illness: A data linkage study.

INTRODUCTION: Delirium is an acute neuro-psychiatric disturbance precipitated by a range of physical stressors, with high morbidity and mortality. Little is known about its relationship with severe mental illness (SMI). METHODS: We conducted a retrospective cohort study using linked data analyses of the UK Clinical Practice Research Datalink (CPRD) and Hospital Episodes Statistics (HES) databases. We ascertained yearly hospital delirium incidence from 2000 to 2017 and used logistic regression to identify associations with delirium diagnosis in a population with SMI. RESULTS: The cohort included 249,047 people with SMI with median follow-up time in CPRD of 6.4 years. A total of 85,979 patients were eligible for linkage to HES. Delirium incidence increased from 0.04 (95% CI 0.02-0.07) delirium associated admissions per 100 person-years in 2000 to 1.05 (95% CI 0.93-1.17) per 100 person-years in 2017, increasing most notably from 2010 onwards. Delirium was associated with older age at study entry (OR 1.05 per year, 95% CI 1.05-1.06), SMI diagnosis of bipolar affective disorder (OR 1.66, 95% CI 1.44-1.93) or other psychosis (OR 1.56, 95% CI 1.35-1.80) relative to schizophrenia, and more physical comorbidities (OR 1.08 per additional comorbidity of the Charlson Comorbidity Index, 95% CI 1.02-1.14). Patients with delirium received more antipsychotic medication during follow-up (1-2 antipsychotics OR 1.65, 95% CI 1.44-1.90; >2 antipsychotics OR 2.49, 95% CI 2.12-2.92). CONCLUSIONS: The incidence of recorded delirium diagnoses in people with SMI has increased in recent years. Older people prescribed more antipsychotics and with more comorbidities have a higher incidence. Linked electronic health records are feasible for exploring hospital diagnoses such as delirium in SMI.

Post-traumatic stress disorder as a risk factor for dementia: systematic review and meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been identified as a potential risk factor for developing dementia. There are currently, however, no meta-analyses quantifying this risk. AIMS: To systematically review and quantify the risk of future dementia associated with PTSD across populations. PROSPERO registration number CRD42019130392. METHOD: We searched nine electronic databases up to 25 October 2019 for longitudinal studies assessing PTSD and risk of dementia. We used random- and fixed-effects meta-analyses to pool estimates across studies. RESULTS: PTSD was associated with a significant risk for all-cause dementia: pooled hazard ratio HR = 1.61 (95% CI 1.43-1.81, I2= 85.8%, P < 0.001; n = 1 693 678; 8 studies). Pooled HR was 1.61 (95% CI 1.46-1.78; I2= 80.9%, P < 0.001; n = 905 896; 5 studies) in veterans, and 2.11 (95% CI 1.03-4.33, I2= 91.2%, P < 0.001; n = 787 782; 3 studies) in the general population. The association between PTSD and dementia remained significant after excluding studies with high risk of bias (HR = 1.55, 95% CI 1.39-1.73, I2= 83.9%, P < 0.001; n = 1 684 928; 7 studies). Most studies included were retrospective and there was evidence of high heterogeneity. CONCLUSIONS: This is the first meta-analysis quantifying the association of PTSD and risk of dementia showing that PTSD is a strong and potentially modifiable risk factor for all-cause dementia. Future studies investigating potential causal mechanisms, and the protective value of treating PTSD are needed.

Prevalence of anxiety disorders and symptoms in people with hearing impairment: a systematic review.

PURPOSE: Anxiety disorders are common. Prevalence is likely to be raised in people with hearing impairment, who experience higher rates of associated risk factors. We conducted, to our knowledge, the first systematic review of the prevalence and correlates of anxiety in people with hearing impairment. METHODS: We searched electronic databases and references of included studies, using predetermined criteria to retrieve original research reporting prevalence of anxiety disorders or symptoms in adult, hearing impaired populations. We assessed risk of bias using the adapted Newcastle Ottawa Scale. RESULTS: We included 25 studies evaluating 17,135 people with hearing impairment. Community studies of higher quality reported a lifetime prevalence of anxiety disorder of 11.1% (one study) and point prevalences of 15.4-31.3% for clinically significant anxiety symptoms (five studies) in people who predominantly had acquired hearing impairment. Anxiety prevalence was higher in hearing impaired people in 8/10 studies with a comparator non-hearing impaired group. Anxiety symptoms decreased after surgical intervention for hearing in all studies investigating this. Correlates consistently associated with anxiety were tinnitus and hearing impairment severity. CONCLUSIONS: Prevalence of anxiety is higher among people with hearing impairment than the general population; our findings indicate that this excess morbidity may be related to the hearing impairment itself, as it was associated with the severity of impairment, and reduced after surgical treatment. Clinicians should be aware of the potential impact of hearing on mental health, and that where hearing ability can be improved, this may reduce anxiety. PROSPERO REGISTRATION NUMBER: CRD42018088463.

Ambulatory intracranial pressure in humans: ICP increases during movement between body positions.

Introduction: Positional changes in intracranial pressure (ICP) have been described in humans when measured over minutes or hours in a static posture, with ICP higher when lying supine than when sitting or standing upright. However, humans are often ambulant with frequent changes in position self-generated by active movement. Research question: We explored how ICP changes during movement between body positions. Material and methods: Sixty-two patients undergoing clinical ICP monitoring were recruited. Patients were relatively well, ambulatory and of mixed age, body habitus and pathology. We instructed patients to move back and forth between sitting and standing or lying and sitting positions at 20 s intervals after an initial 60s at rest. We simultaneously measured body position kinematics from inertial measurement units and ICP from an intraparenchymal probe at 100 Hz. Results: ICP increased transiently during movements beyond the level expected by body position alone. The amplitude of the increase varied between participants but was on average ∼5 mmHg during sit-to-stand, stand-to-sit and sit-to-lie movements and 10.8 mmHg [95%CI: 9.3,12.4] during lie-to-sit movements. The amplitude increased slightly with age, was greater in males, and increased with median 24-h ICP. For lie-to-sit and sit-to-lie movements, higher BMI was associated with greater mid-movement increase (ß = 0.99 [0.78,1.20]; ß = 0.49 [0.34,0.64], respectively). Discussion and conclusion: ICP increases during movement between body positions. The amplitude of the increase in ICP varies with type of movement, age, sex, and BMI. This could be a marker of disturbed ICP dynamics and may be particularly relevant for patients with CSF-diverting shunts in situ.

Factors predicting amoxicillin prescribing in primary care among children: a cohort study.

BACKGROUND: Antibiotic prescribing during childhood, most commonly for respiratory tract infections (RTIs), contributes to antimicrobial resistance, which is a major public health concern. AIM: To identify factors associated with amoxicillin prescribing and RTI consultation attendance in young children in primary care. DESIGN AND SETTING: Cohort study in Bradford spanning pregnancy to age 24 months, collected 2007-2013, linked to electronic primary care and air pollution data. METHOD: Amoxicillin prescribing and RTI consultation rates/1000 child-years were calculated. Mixed-effects logistic regression models were fitted with general practice (GP) surgery as the random effect. RESULTS: The amoxicillin prescribing rate among 2493 children was 710/1000 child-years during year 1 (95% confidence interval [CI] = 677 to 744) and 780/1000 (95% CI = 745 to 816) during year 2. During year 1, odds of amoxicillin prescribing were higher for boys (adjusted odds ratio [aOR] 1.36, 95% CI = 1.14 to 1.61), infants from socioeconomically deprived households (aOR 1.36, 95% CI = 1.00 to 1.86), and infants with a Pakistani ethnic background (with mothers born in the UK [aOR 1.44, 95% CI = 1.06 to 1.94] and outside [aOR 1.42, 95% CI = 1.07 to 1.90]). During year 2, odds of amoxicillin prescribing were higher for infants with a Pakistani ethnic background (with mothers born in the UK [aOR 1.46, 95% CI = 1.10 to 1.94] and outside [aOR 1.56, 95% CI = 1.19 to 2.04]) and those born <39 weeks gestation (aOR 1.20, 95% CI = 1.00 to 1.45). Additional risk factors included caesarean delivery, congenital anomalies, overcrowding, birth season, and childcare attendance, with GP surgery explaining 7%-9% of variation. CONCLUSION: Socioeconomic status and ethnic background were associated with amoxicillin prescribing during childhood. Efforts to reduce RTI spread in household and childcare settings may reduce antibiotic prescribing in primary care.

SARS-CoV-2 tests, confirmed infections and COVID-19-related hospital admissions in children and young people: birth cohort study.

BACKGROUND: There have been no population-based studies of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19-related hospital admissions across the full paediatric age range. We examine the epidemiology of SARS-CoV-2 in children and young people (CYP) aged <23 years. METHODS: We used a birth cohort of all children born in Scotland since 1997, constructed via linkage between vital statistics, hospital records and SARS-CoV-2 surveillance data. We calculated risks of tests and PCR-confirmed infections per 1000 CYP-years between August and December 2020, and COVID-19-related hospital admissions per 100 000 CYP-years between February and December 2020. We used Poisson and Cox proportional hazards regression models to determine risk factors. RESULTS: Among the 1 226 855 CYP in the cohort, there were 378 402 tests (a rate of 770.8/1000 CYP-years (95% CI 768.4 to 773.3)), 19 005 PCR-confirmed infections (179.4/1000 CYP-years (176.9 to 182.0)) and 346 admissions (29.4/100 000 CYP-years (26.3 to 32.8)). Infants had the highest COVID-19-related admission rates. The presence of chronic conditions, particularly multiple types of conditions, was strongly associated with COVID-19-related admissions across all ages. Overall, 49% of admitted CYP had at least one chronic condition recorded. CONCLUSIONS: Infants and CYP with chronic conditions are at highest risk of admission with COVID-19. Half of admitted CYP had chronic conditions. Studies examining COVID-19 vaccine effectiveness among children with chronic conditions and whether maternal vaccine during pregnancy prevents COVID-19 admissions in infants are urgently needed.

Readmission after discharge from acute mental healthcare among 231 988 people in England: cohort study exploring predictors of readmission including availability of acute day units in local areas.

BACKGROUND: In the UK, acute mental healthcare is provided by in-patient wards and crisis resolution teams. Readmission to acute care following discharge is common. Acute day units (ADUs) are also provided in some areas. AIMS: To assess predictors of readmission to acute mental healthcare following discharge in England, including availability of ADUs. METHOD: We enrolled a national cohort of adults discharged from acute mental healthcare in the English National Health Service (NHS) between 2013 and 2015, determined the risk of readmission to either in-patient or crisis teams, and used multivariable, multilevel logistic models to evaluate predictors of readmission. RESULTS: Of a total of 231 998 eligible individuals discharged from acute mental healthcare, 49 547 (21.4%) were readmitted within 6 months, with a median time to readmission of 34 days (interquartile range 10-88 days). Most variation in readmission (98%) was attributable to individual patient-level rather than provider (trust)-level effects (2.0%). Risk of readmission was not associated with local availability of ADUs (adjusted odds ratio 0.96, 95% CI 0.80-1.15). Statistically significant elevated risks were identified for participants who were female, older, single, from Black or mixed ethnic groups, or from more deprived areas. Clinical predictors included shorter index admission, psychosis and being an in-patient at baseline. CONCLUSIONS: Relapse and readmission to acute mental healthcare are common following discharge and occur early. Readmission was not influenced significantly by trust-level variables including availability of ADUs. More support for relapse prevention and symptom management may be required following discharge from acute mental healthcare.

Air Pollution, housing and respirfatory tract Infections in Children: NatIonal birth Cohort study (PICNIC): study protocol.

INTRODUCTION: Respiratory tract infections (RTIs) are the most common reason for hospital admission among children <5 years in the UK. The relative contribution of ambient air pollution exposure and adverse housing conditions to RTI admissions in young children is unclear and has not been assessed in a UK context. METHODS AND ANALYSIS: The aim of the PICNIC study (Air Pollution, housing and respiratory tract Infections in Children: NatIonal birth Cohort Study) is to quantify the extent to which in-utero, infant and childhood exposures to ambient air pollution and adverse housing conditions are associated with risk of RTI admissions in children <5 years old. We will use national administrative data birth cohorts, including data from all children born in England in 2005-2014 and in Scotland in 1997-2020, created via linkage between civil registration, maternity and hospital admission data sets. We will further enhance these cohorts via linkage to census data on housing conditions and socioeconomic position and small area-level data on ambient air pollution and building characteristics. We will use time-to-event analyses to examine the association between air pollution, housing characteristics and the risk of RTI admissions in children, calculate population attributable fractions for ambient air pollution and housing characteristics, and use causal mediation analyses to explore the mechanisms through which housing and air pollution influence the risk of infant RTI admission. ETHICS, EXPECTED IMPACT AND DISSEMINATION: To date, we have obtained approval from six ethics and information governance committees in England and two in Scotland. Our results will inform parents, national and local governments, the National Health Service and voluntary sector organisations of the relative contribution of adverse housing conditions and air pollution to RTI admissions in young children. We will publish our results in open-access journals and present our results to the public via parent groups and social media and on the PICNIC website. Code and metadata will be published on GitHub.

Birth Defects After Exposure to Efavirenz-Based Antiretroviral Therapy at Conception/First Trimester of Pregnancy: A Multicohort Analysis.

BACKGROUND: To investigate the association between efavirenz (EFV) use during conception or first trimester (T1) of pregnancy and the occurrence of birth defects. SETTING: Seven observational studies of pregnant HIV-positive women across 13 European countries and Thailand. METHODS: Individual-level data were pooled on singleton pregnancies included in participating cohorts in 2002-2015. Birth defects were coded according to ICD-10 and the EUROCAT classification. We performed mixed-effects logistic regression models to assess the association between EFV exposure in utero and likelihood of birth defects. RESULTS: We included 24,963 live births from 21,093 women. At conception, 30.2% (7537) women were on a non-EFV-based regimen, 4.8% (1200) on EFV, and 65% (16,226) were unexposed to antiretroviral therapy (ART). There were 412 infants with ≥1 birth defect, a prevalence of 1.65% (95% confidence interval: 1.50 to 1.82). Limb/musculoskeletal and congenital heart defects were the most common defects reported. Birth defects were present in 2.4%, 1.6%, and 1.3% of infants exposed to non-EFV, EFV, and unexposed to ART during conception/T1 (P = 0.135), respectively. The association between exposure to ART during conception/T1 and birth defects remained nonsignificant in adjusted analyses, as did exposure to EFV versus non-EFV (adjusted odds ratio 0.61; 95% confidence interval: 0.36 to 1.03, P = 0.067). Among the 21 birth defects in 19 infants on EFV, no neural tube defects were reported. CONCLUSIONS: Prevalence of birth defects after exposure to EFV-based compared with non-EFV-based ART in conception/T1 was not statistically different in this multicohort study, and even lower. EFV is at least as safe as other ART drugs currently recommended for antenatal use.

Stillbirth in Women Living With HIV Delivering in the United Kingdom and Ireland: 2007-2015.

BACKGROUND: Women living with HIV have a higher risk of adverse birth outcomes, but questions remain regarding their specific risk factors for stillbirth and the extent to which maternal HIV is associated with stillbirth. METHODS: Using data on pregnant women with HIV reported within population-based surveillance in the United Kingdom/Ireland, we described stillbirth rates in 2007-2015 stratified by type of antiretroviral therapy (ART) and evaluated risk factors using Poisson regression. General population stillbirth rates by maternal world region of origin were derived from national annual birth statistics, and compared with rates in women with HIV, using standardized stillbirth ratios with the general population as the reference. RESULTS: Between 2007 and 2015, there were 10,434 singleton deliveries in 8090 women with HIV; 75% of pregnancies were in women of African origin; and 49% were conceived on ART. The stillbirth rate was 8.5 (95% confidence interval: 6.9 to 10.5) per 1000 births. Risk factors for stillbirth included pre-eclampsia, diabetes, Asian maternal origin (versus United Kingdom/Ireland), CD4 count <350 cells/mm, older maternal age, and primiparity. Conceiving on ART did not increase the risk. The stillbirth rates (per 1000 births) by type of ART were 14.3, 11.7, 8.3, and 6.0, respectively for NVP + XTC/TDF-, LPV/r + 3TC/ZDV-, NVP + XTC/ABC-, and NVP + XTC/ZDV-exposed pregnancies (P value = 0.40). The standardized stillbirth ratio was 129 (95% confidence interval: 101 to 165) in women with HIV compared with the general population. CONCLUSION: After adjusting for maternal origin, the stillbirth rate remained higher in women with HIV than the general population. We recommend further studies to understand and prevent this excess.

Protease inhibitors and preterm delivery: another piece in the puzzle.

BACKGROUND: Questions remain regarding preterm delivery (PTD) risk in HIV-infected women on antiretroviral therapy (ART), including the role of ritonavir (RTV)-boosted protease inhibitors, timing of ART initiation and immune status. METHODS: We examined data from the UK/Ireland National Study of HIV in Pregnancy and Childhood on women with HIV delivering a singleton live infant in 2007-2015, including those pregnancies receiving RTV-boosted protease inhibitor-based (n = 4184) or nonnucleoside reverse transcriptase inhibitors-based regimens (n = 1889). We conducted logistic regression analysis adjusted for risk factors associated with PTD and stratified by ART at conception and CD4 cell count to minimize bias by indication for treatment and to assess whether PTD risk differs by ART class and specific drug combinations. RESULTS: Among women conceiving on ART, lopinavir/RTV was associated with increased PTD risk in those with CD4 cell count 350 cells/µl or less [odds ratio 1.99 (1.02, 3.85)] and with CD4 cell count more than 350 cells/µl [odds ratio 1.61 (1.07, 2.43)] vs. women on nonnucleoside reverse transcriptase inhibitors-based (mainly efavirenz and nevirapine) regimens in the same CD4 subgroup. Associations between other protease inhibitor-based regimens (mainly atazanavir and darunavir) and PTD risk were complex. Overall, PTD risk was higher in women who conceived on ART, had low CD4 cell count and were older. No trend of association of PTD with tenofovir or any specific drug combinations was observed. CONCLUSION: Our data support a link between the initiation of RTV-boosted/lopinavir-based ART preconception and PTD in subsequent pregnancies, with implications for treatment guidelines. Continued monitoring of PTD risk is needed as increasing numbers of pregnancies are conceived on new drugs.

Traffic-related pollution and asthma prevalence in children. Quantification of associations with nitrogen dioxide.

Ambient nitrogen dioxide is a widely available measure of traffic-related air pollution and is inconsistently associated with the prevalence of asthma symptoms in children. The use of this relationship to evaluate the health impact of policies affecting traffic management and traffic emissions is limited by the lack of a concentration-response function based on systematic review and meta-analysis of relevant studies. Using systematic methods, we identified papers containing quantitative estimates for nitrogen dioxide and the 12 month period prevalence of asthma symptoms in children in which the exposure contrast was within-community and dominated by traffic pollution. One estimate was selected from each study according to an a priori algorithm. Odds ratios were standardised to 10 µg/m3 and summary estimates were obtained using random- and fixed-effects estimates. Eighteen studies were identified. Concentrations of nitrogen dioxide were estimated for the home address (12) and/or school (8) using a range of methods; land use regression (6), study monitors (6), dispersion modelling (4) and interpolation (2). Fourteen studies showed positive associations but only two associations were statistically significant at the 5 % level. There was moderate heterogeneity (I2 = 32.8 %) and the random-effects estimate for the odds ratio was 1.06 (95 % CI 1.00 to 1.11). There was no evidence of small study bias. Individual studies tended to have only weak positive associations between nitrogen dioxide and asthma prevalence but the summary estimate bordered on statistical significance at the 5 % level. Although small, the potential impact on asthma prevalence could be considerable because of the high level of baseline prevalence in many cities. Whether the association is causal or indicates the effects of a correlated pollutant or other confounders, the estimate obtained by the meta-analysis would be appropriate for estimating impacts of traffic pollution on asthma prevalence.