Serum Antibody Levels to the Pneumocystis jirovecii Major Surface Glycoprotein in the Diagnosis of P. jirovecii Pneumonia in HIV+ Patients

infection has never been developed. major surface glycoprotein recombinant fragment C1 (MsgC1) in 110 HIV+ patients with active PcP (cases) and 63 HIV+ patients with pneumonia due to other causes (controls) by an enzyme-linked immunosorbent assay (ELISA). The cases had significantly higher IgG and IgM antibody levels to MsgC1 than the controls at hospital admission (week 0) and intervals up to at least 1 month thereafter. The sensitivity, specificity and positive predictive value (PPV) of IgG antibody levels increased from 57.2%, 61.7% and 71.5% at week 0 to 63.4%, 100%, and 100%, respectively, at weeks 3–4. The sensitivity, specificity and PPV of IgM antibody levels rose from 59.7%, 61.3%, and 79.3% at week 0 to 74.6%, 73.7%, and 89.8%, respectively, at weeks 3–4. Multivariate analysis revealed that a diagnosis of PcP was the only independent predictor of high IgG and IgM antibody levels to MsgC1. A high LDH level, a nonspecific marker of lung damage, was an independent predictor of low IgG antibody levels to MsgC1.The results suggest that the ELISA shows promise as an aid to the diagnosis of PCP in situations where diagnostic procedures cannot be performed. Further studies in other patient populations are needed to better define the usefulness of this serologic test

Early morbidities following paediatric cardiac surgery: a mixed-methods study

BackgroundOver 5000 paediatric cardiac surgeries are performed in the UK each year and early survival has improved to > 98%.ObjectivesWe aimed to identify the surgical morbidities that present the greatest burden for patients and health services and to develop and pilot routine monitoring and feedback.Design and settingOur multidisciplinary mixed-methods study took place over 52 months across five UK paediatric cardiac surgery centres.ParticipantsThe participants were children aged MethodsWe reviewed existing literature, ran three focus groups and undertook a family online discussion forum moderated by the Children’s Heart Federation. A multidisciplinary group, with patient and carer involvement, then ranked and selected nine key morbidities informed by clinical views on definitions and feasibility of routine monitoring. We validated a new, nurse-administered early warning tool for assessing preoperative and postoperative child development, called the brief developmental assessment, by testing this among 1200 children. We measured morbidity incidence in 3090 consecutive surgical admissions over 21 months and explored risk factors for morbidity. We measured the impact of morbidities on quality of life, clinical burden and costs to the NHS and families over 6 months in 666 children, 340 (51%) of whom had at least one morbidity. We developed and piloted methods suitable for routine monitoring of morbidity by centres and co-developed new patient information about morbidities with parents and user groups.ResultsFamilies and clinicians prioritised overlapping but also different morbidities, leading to a final list of acute neurological event, unplanned reoperation, feeding problems, renal replacement therapy, major adverse events, extracorporeal life support, necrotising enterocolitis, surgical infection and prolonged pleural effusion. The brief developmental assessment was valid in children aged between 4 months and 5 years, but not in the youngest babies or 5- to 17-year-olds. A total of 2415 (78.2%) procedures had no measured morbidity. There was a higher risk of morbidity in neonates, complex congenital heart disease, increased preoperative severity of illness and with prolonged bypass. Patients with any morbidity had a 6-month survival of 81.5% compared with 99.1% with no morbidity. Patients with any morbidity scored 5.2 points lower on their total quality of life score at 6 weeks, but this difference had narrowed by 6 months. Morbidity led to fewer days at home by 6 months and higher costs. Extracorporeal life support patients had the lowest days at home (median: 43 days out of 183 days) and highest costs (£71,051 higher than no morbidity).LimitationsMonitoring of morbidity is more complex than mortality, and hence this requires resources and clinician buy-in.ConclusionsEvaluation of postoperative morbidity provides important information over and above 30-day survival and should become the focus of audit and quality improvement.Future workNational audit of morbidities has been initiated. Further research is needed to understand the implications of feeding problems and renal failure and to evaluate the brief developmental assessment.FundingThis project was funded by the NIHR Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 30. See the NIHR Journals Library website for further project information.Katherine L Brown is a member of the Health Technology Assessment (HTA) Clinical Trials Board (2017–21) and a member of the domain expert group of the National Congenital Heart Diseases Audit (2014–19). David L Barron is a member of the National Congenital Heart Disease Audit Steering Committee (2014–18). Monica Lakhanpaul is part of the following boards or panels: HTA Maternal, Neonatal and Child Health (MNCH) Methods Group, HTA MNCH Panel (2012–17) and Psychological and Community Therapies Panel (2012–15). Steve Morris has been a member of the following boards or panels: Health Services and Delivery Research (HSDR) Board Members (2014–18), HSDR Commissioned Board Members, HSDR Evidence Synthesis Sub Board 2016 and the Public Health Research Research Funding Board (2011–17). Thomas Witter was a member of the National Congenital Heart Disease Audit Steering Committee (2014–18). The research reported in this issue of the journal was funded by the HS&DR programme or one of its preceding programmes as project number 12/5005/06

Period and Cohort Changes in Americans’ Support for Marijuana Legalization: Convergence and Divergence across Social Groups

We cast fresh light on how and why Americans’ views on marijuana legalization shifted between 1973 and 2014. Results from age-period-cohort models show a strong negative effect of age and relatively high levels of support for legalization among baby boom cohorts. Despite the baby boom effect, the large increase in support for marijuana legalization is predominantly a broad, period-based change in the population. Additional analyses demonstrate that differences in support for legalization by education, region, and religion decline, that differences by political party increase, and that differences between whites and African Americans reverse direction. We conclude by discussing the implications of these findings and by identifying promising directions for future research on this topic

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Individual variation in corticosterone and personality traits in the blue tit Cyanistes caeruleus

Source: Variation in personality traits is predicted to reflect physiology, but the extent to which variations in stress hormones derive from differences in personality and/or state-dependent factors remains unclear. To investigate this, wild blue tits (Cyanistes caeruleus) were briefly brought into captivity and scored for personality and corticosterone (Cort) concentrations. More active females had lower baseline Cort than less active individuals. Exploratory tendency and neophobia did not co-vary with baseline Cort. Stress-induced Cort concentrations were correlated negatively with exploratory tendency and haematocrit, but positively with mass gain in captivity. Therefore, baseline and stress-induced Cort concentrations in wintering blue tits were associated with state-dependent variables, sex, age and personality traits. Key to interpreting the physiology of personality traits seems to be their interactions with other traits that mediate ability to utilise resources, and thus influence an individual’s perception of its current and future energy balance

Belief Shift or Only Facilitation: How Semantic Expectancy Affects Processing of Speech Degraded by Background Noise

Individuals use semantic expectancy – applying conceptual and linguistic knowledge to speech input – to improve the accuracy and speed of language comprehension. This study tested how adults use semantic expectancy in quiet and in the presence of speech-shaped broadband noise at -7 and -12 dB signal-to-noise ratio. Twenty-four adults (22.1 ± 3.6 years, mean ±SD) were tested on a four-alternative-forced-choice task whereby they listened to sentences and were instructed to select an image matching the sentence-final word. The semantic expectancy of the sentences was unrelated to (neutral), congruent with, or conflicting with the acoustic target. Congruent expectancy improved accuracy and conflicting expectancy decreased accuracy relative to neutral, consistent with a theory where expectancy shifts beliefs toward likely words and away from unlikely words. Additionally, there were no significant interactions of expectancy and noise level when analyzed in log-odds, supporting the predictions of ideal observer models of speech perception

Oral and airway microbiota in HIV-infected pneumonia patients.

Despite the increased frequency of recurrent pneumonia in HIV-infected patients and recent studies linking the airway bacterial community (microbiota) to acute and chronic respiratory infection, little is known of the oral and airway microbiota that exist in these individuals and their propensity to harbor pathogens despite antimicrobial treatment for acute pneumonia. This pilot study compared paired samples of the oral and airway microbiota from 15 hospitalized HIV-infected patients receiving antimicrobial treatment for acute pneumonia. Total DNA was extracted, bacterial burden was assessed by quantitative PCR, and amplified 16S rRNA was profiled for microbiome composition using a phylogenetic microarray (16S rRNA PhyloChip). Though the bacterial burden of the airway was significantly lower than that of the oral cavity, microbiota in both niches were comparably diverse. However, oral and airway microbiota exhibited niche specificity. Oral microbiota were characterized by significantly increased relative abundance of multiple species associated with the mouth, including members of the Bacteroides, Firmicutes, and TM7 phyla, while airway microbiota were primarily characterized by a relative expansion of the Proteobacteria. Twenty-two taxa were detected in both niches, including Streptococcus bovis and Chryseobacterium species, pathogens associated with HIV-infected populations. In addition, we compared the airway microbiota of five of these patients to those of five non-HIV-infected pneumonia patients from a previous study. Compared to the control population, HIV-infected patients exhibited relative increased abundance of a large number of phylogenetically distinct taxa, which included several known or suspected pathogenic organisms, suggesting that recurrent pneumonia in HIV-infected populations may be related to the presence of these species

Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study.

ObjectiveTo evaluate vaginal, endometrial, and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy (HT).DesignThis was a 1-year, randomized, double-blind, placebo-controlled trial of 351 women, ages 45 to 55, with two or more vasomotor symptoms per day. Women were randomly assigned to (1) black cohosh, (2) a multibotanical containing black cohosh, (3) the same multibotanical plus dietary soy counseling, (4) HT, or (5) placebo. Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month. Data on vaginal cytology and dryness were collected (at baseline and 3 and 12 mo). Daily menstrual diaries were maintained by 313 women with a uterus, and abnormal bleeding was evaluated. Serum estradiol, follicle-stimulating hormone, luteinizing hormone, and steroid hormone-binding globulin were assessed (baseline and 12 mo) among 133 postmenopausal women. Gynecologic outcomes of the five groups were compared.ResultsThe five groups did not vary in baseline vaginal cytology profiles, vaginal dryness, menstrual cyclicity, or hormone profiles. The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months (P < 0.05). Abnormal bleeding occurred in 53 of 313 (16.9%) women. There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups, whereas women in the HT group had a greater risk than those in the placebo group (P < 0.001). Among postmenopausal women, HT significantly decreased follicle-stimulating hormone and increased estradiol; none of the herbal interventions showed significant effects on any outcomes at any time point.ConclusionBlack cohosh, used alone or as part of a multibotanical product with or without soy dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones