Causes of hypercapnic respiratory failure and associated in-hospital mortality.

BACKGROUND AND OBJECTIVE: Hypercapnic respiratory failure (HRF) can occur due to severe respiratory disease but also because of multiple coexistent causes. There are few data on the prevalence of antecedent causes for HRF and the effect of these causes on prognosis, especially where study inclusion has not been biased with respect to primary diagnosis, interventions received or clinical outcome. We sought to determine the prevalence of pre-specified conditions among patients with HRF and to determine the effect of these causes on in-hospital mortality. METHODS: Cross-sectional study of patients with HRF from 2013 to 2017. Inclusion criteria were PaCO2  >45 mm Hg and pH ≤7.45. Causes of interest were identified using diagnosis codes from hospital records. We used directed acyclic graphs to inform logistic regression models for the outcome of in-hospital death. RESULTS: We identified 873 persons with HRF in the study period. Mean (SD) age was 69 years and 50.4% were males. Acidosis (pH <7.35) was present in 488 (55%) cases. Most (83%) had one or more of the following: obstructive lung disease, lower respiratory tract infection, congestive cardiac failure, sleep disordered breathing, neuromuscular disease, opioid or benzodiazepine use. In-hospital mortality was 12.8%. Obstructive lung disease and cardiac failure were associated with a lower risk of death, whereas respiratory tract infection and neuromuscular disease were associated with increased risk of death. CONCLUSION: HRF is associated with a range of potentially causative conditions, which significantly impact hospital survival. Systematic evaluation of patients with HRF may increase detection of treatable comorbidities.

Causes of hypercapnic respiratory failure: a population-based case-control study.

OBJECTIVE: There are no population-based data on the relative importance of specific causes of hypercapnic respiratory failure (HRF). We sought to quantify the associations between hospitalisation with HRF and potential antecedent causes including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and congestive cardiac failure. We used data on the prevalence of these conditions to estimate the population attributable fraction for each cause. METHODS: A case-control study was conducted among residents aged ≥ 40 years from the Liverpool local government area in Sydney, Australia. Cases were identified from hospital records based on PaCO2 > 45 mmHg. Controls were randomly selected from the study population using a cluster sampling design. We collected self-reported data on medication use and performed spirometry, limited-channel sleep studies, venous sampling for N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and sniff nasal inspiratory pressure (SNIP) measurements. Logistic regression analyses were performed using directed acyclic graphs to identify covariates. RESULTS: We recruited 42 cases and 105 controls. HRF was strongly associated with post-bronchodilator airflow obstruction, elevated NT-proBNP levels, reduced SNIP measurements and self-reported opioid medication use. There were no differences in the apnoea-hypopnea index or oxygen desaturation index between groups. COPD had the highest population attributable fraction (42%, 95% confidence interval 18% to 59%). CONCLUSIONS: COPD, congestive cardiac failure, and self-reported use of opioid medications, but not obstructive sleep apnea, are important causes of HRF among adults over 40 years old. No single cause accounts for the majority of cases based on the population attributable fraction.

Tree pollen exposure is associated with reduced lung function in children.

BACKGROUND: Allergic disease is a recognized global epidemic and a significant cause of ill health and poor quality of life. The prevalence of pollen allergy is high throughout the world, and pollen exposure itself plays a role in emergency department presentations and hospitalizations for asthma. Lung function and airway inflammation are important measures of asthma activity and control. OBJECTIVE: To examine associations between exposure to multiple pollen types and lung function and markers of airway inflammation at 8 and 14 years of age, and to explore potential modification by residential greenness. METHODS: A cohort of high-risk children living in Sydney, Australia had spirometry and fractional exhaled nitric oxide (FeNO) measured at 8 and 14 years of age. Ambient pollen concentration on the day of lung function measurement and up to three days prior was used as the exposure measure. Residential greenness was derived from satellite imagery. We modelled the association between six pollen types and lung function and FeNO. We also assessed modifying effects of residential greenness. RESULTS: Casuarina, cypress and Pinus pollen in the air the day before measurement and 3 days prior respectively, were associated with reduced lung function in 8-year-olds. The pollen exposures were associated with decreases in FEV1 and FVC; however, the FEV1 /FVC ratio was not affected. Effect modification by greenness was not observed due to loss of power. CONCLUSIONS & CLINICAL RELEVANCE: Airborne tree pollen of cypress, Casuarina and Pinus and not grass in some regions may be detrimental to childhood lung function.

Weight Gain Trajectories from Birth to Adolescence and Cardiometabolic Status in Adolescence.

OBJECTIVE: To assess the influence of the trajectory of weight gain from birth to adolescence on cardiovascular and metabolic risk. We studied childhood body mass index (BMI) trajectories from birth to age 14 years and cardiometabolic risk factors at age 14 years. STUDY DESIGN: In total, 410 children with weight and height measurements were assessed from birth throughout childhood, from the Childhood Asthma Prevention Study, a prospective community-based cohort. BMI trajectory groups were determined by latent basis growth mixture models. Of these subjects, 190 had detailed cardiometabolic risk factors assessed at age 14 years. RESULTS: Three BMI trajectory groups were identified; normal BMI, "early rising" excess BMI from 2 years, and "late rising" excess BMI from 5 years. Differences were found between normal and excess BMI in children at 14 years of age. In addition, children with an early rising BMI trajectory had statistically significantly higher central adiposity and a more atherogenic lipoprotein profile at age 14 years than children with a late rising BMI trajectory (P < .05). No differences between BMI trajectory groups in vascular structure or function was identified at age 14 years. CONCLUSIONS: Earlier onset of an elevated BMI trajectory persisting from birth to age 14 years results in an unfavorable cardiometabolic risk profile at age 14 years, including central adiposity and more atherogenic lipoproteins, independent of achieved BMI.

Asthma and atopy prevalence are not reduced among former tuberculosis patients compared with controls in Lima, Peru.

BACKGROUND: Although there are theoretical reasons for believing that asthma and atopy may be negatively correlated with tuberculosis, epidemiological studies have had conflicting findings. OBJECTIVE: To determine if people with confirmed tuberculosis were less likely to be atopic and less likely to have atopic disease including asthma compared to those with no previous tuberculosis. METHODS: Patients in Lima, Peru with a prior history of tuberculosis were identified from clinic records in this cohort study. A representative sample of individuals without a prior tuberculosis diagnosis was recruited from the same community. Allergen skin prick testing was performed to classify atopic status. Allergic rhinitis was identified by history. Asthma was defined by symptoms and spirometry. Eosinophilic airway inflammation was measured using exhaled nitric oxide levels. RESULTS: We evaluated 177 patients with, and 161 individuals without, previous tuberculosis. There was a lower prevalence of atopy among people with prior tuberculosis on univariate analysis (odds ratio 0.57; 95% confidence interval 0.37-0.88) but, after adjustment for potential confounders, this was no longer statistically significant (aOR 0.64, 95% CI 0.41-1.01). The prevalence of allergic rhinitis (aOR 0.76, 95% CI 0.47 to 1.24 and asthma (aOR 1.18, 95% CI 0.69 to 2.00) did not differ significantly between the two groups. We also found no significant difference in the prevalence of elevated exhaled nitric oxide (aOR 1.30, 95% CI 0.78 to 2.17) or a combined index of atopic disease (aOR 0.86, 95% CI 0.54 to 1.36). CONCLUSION: In this urban environment in a middle-income country, prior tuberculosis may be associated with a reduced risk of atopy but does not protect against asthma and atopic disease.

Impact of childhood asthma on growth trajectories in early adolescence: Findings from the Childhood Asthma Prevention Study (CAPS).

BACKGROUND AND OBJECTIVE: Understanding the associations between childhood asthma and growth in early adolescence by accounting for the heterogeneity of growth during puberty has been largely unexplored. The objective was to identify sex-specific classes of growth trajectories during early adolescence, using a method which takes the heterogeneity of growth into account and to evaluate the association between childhood asthma and different classes of growth trajectories in adolescence. METHODS: Our longitudinal study included participants with a family history of asthma born during 1997-1999 in Sydney, Australia. Hence, all participants were at high risk for asthma. Asthma status was ascertained at 8 years of age using data from questionnaires and lung function tests. Growth trajectories between 11 and 14 years of age were classified using a latent basis growth mixture model. Multinomial regression analyses were used to evaluate the association between asthma and the categorized classes of growth trajectories. RESULTS: In total, 316 participants (51.6% boys), representing 51.3% of the entire cohort, were included. Sex-specific classes of growth trajectories were defined. Among boys, asthma was not associated with the classes of growth trajectories. Girls with asthma were more likely than girls without asthma to belong to a class with later growth (OR: 3.79, 95% CI: 1.33, 10.84). Excluding participants using inhaled corticosteroids or adjusting for confounders did not significantly change the results for either sex. CONCLUSION: We identified sex-specific heterogeneous classes of growth using growth mixture modelling. Associations between childhood asthma and different classes of growth trajectories were found for girls only.

Supine awake oximetry as a screening tool for daytime hypercapnia in super-obese patients.

BACKGROUND: Evidence-based screening tools are required for detection of daytime hypercapnia in high-risk patient populations. AIMS: To determine the validity of supine awake oximetry as a test for daytime hypercapnia and severe sleep disordered breathing (SDB) in super-obese patients. METHODS: This was a cross-sectional diagnostic test evaluation of super-obese adults (body mass index >50 kg/m2 ) presenting to Liverpool Hospital, Australia, between 2009 and 2015 for diagnostic polysomnography (PSG) and arterial blood gas measurement. Supine awake oxygen saturation (SpO2 ) was determined using oximetry measurements from the first three awake epochs of raw PSG data. Sensitivity and specificity of SpO2 for detecting patients with daytime hypercapnia (PaCO2 >45 mmHg) and severe SDB (respiratory disturbance index (RDI) >30 events/h) were assessed at various cut-off points and displayed using a receiver operating characteristic (ROC) curve. Area under the ROC curve and positive and negative predictive values (PPV and NPV) in the present patient population were derived. RESULTS: Of 52 patients, 23 (44%) had daytime hypercapnia. SpO2 measured awake in the supine position was associated with the presence of daytime hypercapnia but not with the presence of severe SDB. Overall, awake supine SpO2 <91.2% had 34.8% sensitivity, 96.6% specificity and 88.8% PPV, and SpO2 <96.7% had 87.0% sensitivity, 20.7% specificity and 66.7% NPV for the presence of daytime hypercapnia. CONCLUSION: Awake supine oximetry is an easily performed test that may have novel use in identifying patients at high risk of respiratory failure. Future studies are required to evaluate prospectively its role in screening patients at risk of daytime hypercapnia.

Change in the manifestations of asthma and asthma-related traits in childhood: a latent transition analysis.

It is known that asthma is a heterogeneous entity whose manifestations vary with age. Our objective was to examine changes in the manifestation of asthma and asthma-related traits in childhood by defining empirically derived childhood asthma phenotypes and examining their transitions over time.To define the phenotypes we used data on respiratory symptoms, healthcare utilisation, medications, spirometry, airway hyperresponsiveness (AHR), exhaled nitric oxide concentration and atopy from a birth cohort recruited on the basis of having a first-degree relative with asthma. Data were acquired at ages 1.5-11.5 years and analysed using latent transition analysis.In a study population of 370 participants, we classified subjects into four phenotypes: 1) nonatopic, few symptoms (prevalence range from 1.5 to 5 years: 52-60%), 2) atopic, few symptoms (3-21%), 3) nonatopic, asthma and rhinitis symptoms (13-35%), and 4) atopic, asthma and rhinitis symptoms (2-14%) in early childhood; and 1) nonatopic, no respiratory disease (prevalence range from 8 to 11.5 years: 41-46%), 2) atopic, no respiratory disease (23-33%), 3) nonatopic, asthma symptoms, no AHR or airway inflammation (8-12%) and 4) atopic asthma (19%) in mid-childhood. Transitioning between phenotypes was common in early childhood, but less common in later childhood.This analysis represents the first attempt to incorporate longitudinal patterns of several manifestations of asthma into a single model to simultaneously define phenotypes and examine their transitions over time. It provides quantitative support for the view that asthma is a heterogeneous entity, and that some children with wheeze and other respiratory symptoms in early life progress to asthma in mid-childhood, while others become asymptomatic.

Absence of back to school peaks in human rhinovirus detections and respiratory symptoms in a cohort of children with asthma.

Much of what is known about the seasonality of human rhinovirus (hRV) infections has been learned from the study of acute asthma exacerbations presenting to emergency care, including those among children at the start of the school term. Much less is known about the patterns of hRVs in the community. In this study, viruses and day-to-day symptoms of asthma and colds were monitored twice weekly in 67 children with asthma aged 5-12 years, over a 15 month period in Sydney, Australia. Overall hRV was detected in 314/1232 (25.5%) of nasal wash samples and 142/1231 (11.5%) of exhaled breath samples; of these, 231 and 24 respectively were genotyped. HRVs were detected with similar prevalence rate throughout the year, including no peak in hRV prevalence following return to school. No peaks were seen in asthma and cold symptoms using twice-weekly diary records. However, over the same period in the community, there were peaks in asthma emergency visits both at a large local hospital and in state-wide hospitalizations, following both return to school (February) and in late autumn (May) in children of the same age. This study suggests that hRV infections are common throughout the year among children, and differences in virus prevalence alone may not account for peaks in asthma symptoms.

Cervicitis aetiology and case definition: a study in Australian women attending sexually transmitted infection clinics.

OBJECTIVES: Studies examining cervicitis aetiology and prevalence lack comparability due to varying criteria for cervicitis. We aimed to outline cervicitis associations and suggest a best case definition. METHODS: A cross-sectional study of 558 women at three sexually transmitted infection clinics in Sydney, Australia, 2006-2010, examined pathogen and behavioural associations of cervicitis using three cervicitis definitions: 'microscopy' (>30 pmnl/hpf (polymorphonuclear leucocytes per high-powered field on cervical Gram stain)), 'cervical discharge' (yellow and/or mucopurulent cervical discharge) or 'micro+cervical discharge' (combined 'microscopy' and 'cervical discharge'). RESULTS: Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV) and Neisseria gonorrhoeae (NG) had the strongest associations with cervicitis definitions 'micro+cervical discharge': CT adjusted prevalence ratio (APR)=2.13 (95% CI 1.38 to 3.30) p=0.0006, MG APR=2.21 (1.33 to 3.69) p=0.002, TV APR=2.37 (1.44 to 3.90) p=0.0007 NG PR=4.42 (3.79 to 5.15) p<0.0001 and 'cervical discharge': CT APR=1.90 (1.25 to 2.89) p=0.003, MG APR=1.93 (1.17 to 3.19) p=0.011, TV APR=2.02 (1.24 to 3.31) p=0.005 NG PR=3.88 (3.36 to 4.48) p<0.0001. Condom use for vaginal sex 'always/sometimes' reduced cervicitis risk: ('micro+cervical discharge') APR=0.69 (0.51 to 0.93) p=0.016. Combined population attributable risk % (PAR%) of these four pathogens was only 18.0% with a protective PAR% of condoms of 25.7%. Exposures not associated with cervicitis included bacterial vaginosis, Mycoplasma hominis, Ureaplasma urealyticum, herpes simplex virus 1&2, cytomegalovirus, Candida, age, smoking and hormonal contraception. CONCLUSIONS: Cervicitis was associated with CT, MG, TV and NG with combined PAR% of these pathogens only 18% in this setting, suggesting other factors are involved. Condoms significantly reduced cervicitis risk. Cervicitis definitions with best clinical utility and pathogen prediction were 'cervical discharge' and 'micro+cervical discharge'.

Rhinoviruses significantly affect day-to-day respiratory symptoms of children with asthma.

BACKGROUND: Viruses are frequently associated with acute exacerbations of asthma, but the extent to which they contribute to the level of day-to-day symptom control is less clear. OBJECTIVE: We sought to explore the relationship between viral infections, host and environmental factors, and respiratory symptoms in children. METHODS: Sixty-seven asthmatic children collected samples twice weekly for an average of 10 weeks. These included nasal wash fluid and exhaled breath for PCR-based detection of viral RNA, lung function measurements, and records of medication use and asthma and respiratory symptoms in the previous 3 days. Atopy, mite allergen exposure, and vitamin D levels were also measured. Mixed-model regression analyses were performed. RESULTS: Human rhinoviruses (hRVs) were detected in 25.5% of 1232 nasal samples and 11.5% of breath samples. Non-hRV viruses were detected in less than 3% of samples. hRV in nasal samples was associated with asthma symptoms (cough and phlegm: odds ratio = 2.0; 95% CI = 1.4-2.86, P = .0001; wheeze and chest tightness: odds ratio = 2.34, 95% CI = 1.55-3.52, P < .0001) and with cold symptoms, as reported concurrently with sampling and 3 to 4 days later. No differences were found between the 3 hRV genotypes (hRV-A, hRV-B, and hRV-C) in symptom risk. A history of inhaled corticosteroid use, but not atopic status, mite allergen exposure, or vitamin D levels, modified the association between viruses and asthma symptoms. CONCLUSION: The detection of nasal hRV was associated with a significantly increased risk of day-to-day asthma symptoms in children. Host, virus genotype, and environmental factors each had only a small or no effect on the relationship of viral infections to asthma symptoms.

Impact of growth, gonadal hormones, adiposity and the sodium-to-potassium ratio on longitudinal adolescent measures of blood pressure at puberty.

Blood pressure (BP) rises rapidly at puberty. While this is partly due to normal development, factors like excess adiposity and a high intake of dietary sodium relative to potassium may contribute to a true increase in hypertension risk. This study aimed to assess the relative impact of growth, gonadal hormones, adiposity and the sodium-to-potassium ratio (Na:K) on longitudinal BP measures at puberty. This study analysed data from a three-year longitudinal cohort study of pubertal adolescents. Anthropometry, body composition (bio-electrical impedance), serum testosterone and oestradiol (mass spectrometry) were measured annually. Na:K was measured from three-monthly urine samples. These variables were used to predict annual BP measures using mixed modelling and ordinal regression. Data from 325 adolescents (11.7 ± 1.0 y; 55% male) were analysed, showing typical growth patterns at puberty. Systolic BP increased over time in both sexes (p < 0.01), with boys exhibiting a significantly steeper rise compared to girls. Adiposity variables (BMI z-score, percent body fat, fat mass, waist-to-height ratio) strongly and consistently predicted systolic and diastolic BP in both sexes (all p < 0.05). Systolic BP was also significantly and positively related to height (p < 0.05). No associations with BP were identified in either sex for gonadal hormones or Na:K. Similar results were obtained when BP was classified into hypertension categories. Relative to other developmental and diet-related variables tested, adiposity was found to be the strongest most consistent predictor of BP in pubertal adolescents. Findings highlight the importance of dedicated youth obesity management interventions and policy measures for reducing long-term hypertension and cardiovascular disease risks.Australian New Zealand Clinical Trials Registry ACTRN12617000964314.

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis (Mtb) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).

Associations Between Ambient Particulate Air Pollution and Cognitive Function in Indonesian Children Living in Forest Fire-Prone Provinces.

Smoke from forest fires can reach hazardous levels for extended periods of time. We aimed to determine if there is an association between particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) and living in a forest fire-prone province and cognitive function. We used data from the Indonesian Family and Life Survey. Cognitive function was assessed by the Ravens Colored Progressive Matrices (RCPM). We used regression models to estimate associations between PM2.5 and living in a forest fire-prone province and cognitive function. In multivariable models, we found very small positive relationships between PM2.5 levels and RCPM scores (PM2.5 level at year of survey: ß = 0.1%; 95% confidence interval (CI) [0.01, 0.19%]). There were no differences in RCPM scores for children living in forest fire-prone provinces compared with children living in non-forest fire-prone provinces (mean difference = -1.16%, 95% CI [-2.53, 0.21]). RCPM scores were lower for children who had lived in a forest fire-prone province all their lives compared with children who lived in a non-forest fire-prone province all their life (ß = -1.50%; 95% CI [-2.94, -0.07]). Living in a forest fire-prone province for a prolonged period of time negatively affected cognitive scores after adjusting for individual factors.

Feasibility and preliminary efficacy of iConquerFear: a self-guided digital intervention for fear of cancer recurrence.

PURPOSE: Approximately 50% of cancer survivors experience moderate-severe fear of cancer recurrence (FCR). Self-guided digital interventions have potential to address the high level of FCR-related unmet needs at scale, but existing digital interventions have demonstrated variable engagement and efficacy. This study aimed to evaluate the feasibility and preliminary efficacy of iConquerFear, a five-module self-guided digital FCR intervention. METHODS: Eligible curatively treated breast cancer survivors were recruited. Participants reporting clinically significant FCR (≥ 13 on the Fear of Cancer Recurrence Inventory-Short Form; FCRI-SF) were given access to iConquerFear. Feasibility was indicated by > 50% of eligible participants enrolling in iConquerFear and recording moderate (≥ 120 min) or greater usage. Preliminary efficacy was evaluated via changes in self-reported FCR severity, anxiety, depression, intrusions and metacognitions from baseline to immediately and 3 months post-intervention. RESULTS: Fifty-four (83%) of 65 eligible participants enrolled in iConquerFear; six subsequently withdrew. Thirty-nine (83%) participants recorded moderate (n = 24; 120-599 min) or high (n = 15; ≥ 600 min) usage. Engagement levels increased with participant age (p = 0.043), but were lower in participants with higher baseline FCR (p = 0.028). Qualitative feedback indicated engagement was sometimes limited by difficulties with navigation and relating to featured survivors. Participants reported significantly improved FCR (mean reduction (95%CI): baseline to post-intervention - 3.44 (- 5.18, - 1.71), baseline to 3-month follow-up - 4.52 (- 6.25, - 2.78), p = < 0.001). CONCLUSION: iConquerFear is a feasible and potentially efficacious intervention for reducing FCR in breast cancer survivors. Easier navigation and more relatable examples may enhance engagement. IMPLICATIONS FOR CANCER SURVIVORS: iConquerFear may help address moderate but burdensome FCR levels in cancer survivors.

Ability of the LACE index to predict 30-day hospital readmissions in patients with community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Hospital readmissions within 30 days are used as an indicator of quality of hospital care. We aimed to evaluate the ability of the LACE (Length of stay, Acuity of admission, Comorbidities based on Charlson comorbidity score and number of Emergency visits in the last 6 months) index to predict the risk of 30-day readmissions in patients hospitalised for community-acquired pneumonia (CAP). METHODS: In this retrospective cohort study a LACE index score was calculated for patients with a principal diagnosis of CAP admitted to a tertiary hospital in Sydney, Australia. The predictive ability of the LACE score for 30-day readmissions was assessed using receiver operator characteristic curves with C-statistic. RESULTS: Of 3996 patients admitted to hospital for CAP at least once, 8.0% (n=327) died in hospital and 14.6% (n=584) were readmitted within 30 days. 17.8% (113 of 636) of all 30-day readmissions were again due to CAP, followed by readmissions for chronic obstructive pulmonary disease, heart failure and chest pain. The LACE index had moderate discriminative ability to predict 30-day readmission (C-statistic=0.6395) but performed poorly for the prediction of 30-day readmissions due to CAP (C-statistic=0.5760). CONCLUSIONS: The ability of the LACE index to predict all-cause 30-day hospital readmissions is comparable to more complex pneumonia-specific indices with moderate discrimination. For the prediction of 30-day readmissions due to CAP, the performance of the LACE index and modified risk prediction models using readily available variables (sex, age, specific comorbidities, after-hours, weekend, winter or summer admission) is insufficient.

Bumpy and Smoother Pathways of Puberty Hormone Change: A Novel Way to Define Gonadal Hormone Trajectories in Adolescents.

CONTEXT: The study of gonadal hormone effects on adolescent wellbeing has been limited by logistical challenges. Urine hormone profiling offers new opportunities to understand the health and behavioral implications of puberty hormones. OBJECTIVE: To characterize pubertal change in urinary testosterone and estradiol among male and female adolescents, respectively. DESIGN: Three-year prospective cohort study. SETTING: Australian regional community. PARTICIPANTS: 282 (163 male) normally developing adolescents aged 11.8 ± 1.0 years at baseline. MAIN OUTCOME MEASURE: Quarterly urine measurements of testosterone and estradiol (mass spectrometry); annual anthropometric assessment and Tanner stage (TS) self-report. RESULTS: Two-class sigmoidal and quadratic growth mixture models (centered on age at TS3) were identified as best-fit for describing testosterone (male) and estradiol (female) change. Classes 1 (male: 63%; female: 82%) and 2 (male: 37%; female: 18%) were respectively named the "stable" and "unstable" trajectories, characterized by different standard deviation of quarterly hormone change and magnitude of hormone peaks and troughs (all P < 0.001). Compared with class 1 (stable), class 2 males were taller at baseline (154 vs 151 cm), reported earlier and faster TS progression (P < 0.01), and showed higher serum testosterone levels at baseline and 3 years (P ≤ 0.01). Class 2 females exhibited smaller height and weight gains over the 3 years and had higher baseline serum estradiol (249 vs 98 pmol/L; P = 0.002) than class 1. CONCLUSIONS: Adolescents showed 2 distinct urinary gonadal hormone trajectories, characterized by stability of change over time, which were not associated with consistent anthropometric differences. Results provide a methodology for studying gonadal hormone impacts on other aspects of biopsychosocial wellbeing. Identification of potential "at-risk" hormone groups would be important for planning supportive interventions.