Predictors of pneumococcal carriage and the effect of the 13-valent pneumococcal conjugate vaccination in the Western Australian Aboriginal population

Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to prevent invasive pneumococcal disease (IPD) in Western Australian (WA) Aboriginal people in 2001. PCV13 replaced PCV7 in July 2011, covering six additional pneumococcal serotypes; however, IPD rates remained high in Aboriginal people in WA. Upper respiratory tract pneumococcal carriage can precede IPD, and PCVs alter serotype distribution. Methods: To assess the impact of PCV13 introduction, identify emerging serotypes, and assess risk factors for carriage, nasopharyngeal swabs and information on demographic characteristics, health, medication and living conditions from Aboriginal children and adults across WA from August 2008 to November 2014 were collected. Bacteria were cultured using selective media and pneumococcal isolates were serotyped by Quellung reaction. Risk factors were analysed by multivariable logistic regression. Results: One thousand five hundred swabs pre- and 1385 swabs post-PCV13 introduction were collected. Pneumococcal carriage was detected in 66.8% of children 53.2% of 5–14 year-olds post-PCV13, compared with pre-PCV13 prevalence of 72.2% and 49.4%, respectively. The prevalence of PCV13-non-PCV7 serotypes decreased in children 13.5% pre-PCV13 to 5.8% post-PCV13 (p \u3c 0.01), and from 8.4% to 6.1% in children 5–14 years old (p \u3e 0.05). The most common serotypes post-PCV13 were 11A (prevalence 4.0%), 15B (3.5%), 16F (3.5%), and 19F (3.2%). Risk of detection of pneumococcal carriage increased until age 12 months (odds ratio [OR] 4.19, 95% confidence interval [CI] 2.39–7.33), with nasal discharge (OR 2.49 [95% CI 2.00–3.09]), residence in a remote community (OR 2.21 [95% CI 1.67–2.92]) and household crowding (OR 1.36 [95% CI 1.11–1.67]). Recent antibiotic use was negatively associated with pneumococcal carriage (OR 0.48 [95% CI 0.33–0.69]). Complete resistance to penicillin was present among isolates of serotypes 19A (6.0%), 19F (2.3%) and non-serotypeable isolates (1.9%). Serotype 23F and newly emerged serotype 7B isolates showed high rates of resistance to cotrimoxazole, erythromycin and tetracycline (86.9%, 86.9%, 82.0%, respectively for 23F, 100.0%, 100.0% and 93.3% for 7B). Conclusion: Since PCV13 replaced PCV7, carriage of PCV13-non-PCV7 serotypes decreased significantly among childrenold, those most likely to have received PCV13, and to a lesser extent in older people. Known risk factors for carriage including crowding and young age remain in the Aboriginal population

High Nasopharyngeal Carriage of Non-Vaccine Serotypes in Western Australian Aboriginal People Following 10 Years of Pneumococcal Conjugate Vaccination

BackgroundInvasive pneumococcal disease (IPD) continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV) was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA) since 2008 to assess the impact of the 10-year 7vPCV program. MethodsWe collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied regions of WA from August 2008 until June 2011. Specimens were cultured on selective media. Pneumococcal isolates were serotyped by the quellung reaction. ResultsStreptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children <5 years of age, and 34.6%, 22.4% and 27.2% of people ≥5 years. Of 43 pneumococcal serotypes identified, the most common were 19A, 16F and 6C in children <5 years, and 15B, 34 and 22F in older people. 7vPCV serotypes accounted for 14.5% of all serotypeable isolates, 13vPCV for 32.4% and 23vPPV for 49.9%, with little variation across all age groups. Serotypes 1 and 12F were rarely identified, despite causing recent IPD outbreaks in WA. Complete penicillin resistance (MIC ≥2µg/ml) was found in 1.6% of serotype 19A (5.2%), 19F (4.9%) and 16F (3.2%) isolates and reduced penicillin susceptibility (MIC ≥0.125µg/ml) in 24.9% of isolates, particularly 19F (92.7%), 19A (41.3%), 16F (29.0%). Multi-resistance to cotrimoxazole, tetracycline and erythromycin was found in 83.0% of 23F isolates. Among non-serotypeable isolates 76.0% had reduced susceptibility and 4.0% showed complete resistance to penicillin.ConclusionsTen years after introduction of 7vPCV for Aboriginal Australian children, 7vPCV serotypes account for a small proportion of carried pneumococci. A large proportion of circulating serotypes are not covered by any currently licensed vaccine

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Digital interventions to enhance readiness for psychological therapy: scoping review.

BACKGROUND: Psychological therapy is an effective treatment method for mental illness; however, many people with mental illness do not seek treatment or drop out of treatment early. Increasing client uptake and engagement in therapy is key to addressing the escalating global problem of mental illness. Attitudinal barriers, such as a lack of motivation, are a leading cause of low engagement in therapy. Digital interventions to increase motivation and readiness for change hold promise as accessible and scalable solutions; however, little is known about the range of interventions being used and their feasibility as a means to increase engagement with therapy. OBJECTIVE: This review aimed to define the emerging field of digital interventions to enhance readiness for psychological therapy and detect gaps in the literature. METHODS: A literature search was conducted in PubMed, PsycINFO, PsycARTICLES, Scopus, Embase, ACM Guide to Computing Literature, and IEEE Xplore Digital Library from January 1, 2006, to November 30, 2021. The PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) methodology was applied. Publications were included when they concerned a digitally delivered intervention, a specific target of which was enhancing engagement with further psychological treatment, and when this intervention occurred before the target psychological treatment. RESULTS: A total of 45 publications met the inclusion criteria. The conditions included depression, unspecified general mental health, comorbid anxiety and depression, smoking, eating disorders, suicide, social anxiety, substance use, gambling, and psychosis. Almost half of the interventions (22/48, 46%) were web-based programs; the other formats included screening tools, videos, apps, and websites. The components of the interventions included psychoeducation, symptom assessment and feedback, information on treatment options and referrals, client testimonials, expectation management, and pro-con lists. Regarding feasibility, of the 16 controlled studies, 7 (44%) measuring actual behavior or action showed evidence of intervention effectiveness compared with controls, 7 (44%) found no differences, and 2 (12%) indicated worse behavioral outcomes. In general, the outcomes were mixed and inconclusive owing to variations in trial designs, control types, and outcome measures. CONCLUSIONS: Digital interventions to enhance readiness for psychological therapy are broad and varied. Although these easily accessible digital approaches show potential as a means of preparing people for therapy, they are not without risks. The complex nature of stigma, motivation, and individual emotional responses toward engaging in treatment for mental health difficulties suggests that a careful approach is needed when developing and evaluating digital readiness interventions. Further qualitative, naturalistic, and longitudinal research is needed to deepen our knowledge in this area

Comparison between Nasal Swabs and Nasopharyngeal Aspirates for, and Effect of Time in Transit on, Isolation of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis

We assessed the impact of the use of nasal swabs or nasopharyngeal aspirates and the time from specimen collection to storage at −70°C on bacterial isolation. Haemophilus influenzae was isolated significantly less often from swabs than from nasopharyngeal aspirates. Samples in transit for >3 days were half as likely to grow Streptococcus pneumoniae and H. influenzae as those in transit for ≤3 days. There was no statistically significant difference for either Moraxella catarrhalis or Staphylococcus aureus

Crowding and other strong predictors of upper respiratory tract carriage of otitis media-related bacteria in Australian aboriginal and non-aboriginal children

Background: Streptococcus pneumoniae, Moraxella catarrhalis, and nontypeable Haemophilus influenzae is associated with otitis media (OM). Data are limited on risk factors for carriage of these pathogens, particularly for Indigenous populations. We investigated predictors of nasopharyngeal carriage in Australian Aboriginal and non-Aboriginal children. Methods: Nasopharyngeal aspirates were collected up to 7 times before age 2 years from 100 Aboriginal and 180 non-Aboriginal children. Longitudinal modeling estimated effects of environmental factors and concurrent carriage of other bacteria on the probability of bacterial carriage. We present a novel method combining the effects of number of household members and size of house into an overall crowding model. Results: Each additional household member increased the risk of carriage of S. pneumoniae (odds ratio [OR] = 1.45 per additional Aboriginal child in a 4-room house, 95% confidence interval [CI]: 1.15-1.84; OR = 2.34 per additional non-Aboriginal child, 95% CI: 1.76-3.10), with similar effect sizes for M. catarrhalis, and nontypeable Haemophilus influenzae. However, living in a larger house attenuated this effect among Aboriginal children. Daycare attendance predicted carriage of the 3 OM-associated bacteria among non-Aboriginal children. Exclusive breast-feeding at 6 to 8 weeks protected against Streptococcus aureus carriage (OR = 0.42, 95% CI: 0.19-0.90 in Aboriginal children and OR = 0.49, 95% CI: 0.25-0.96 in non-Aboriginal children). OM-associated bacteria were more likely to be present if there was concurrent carriage of the other OM-associated species. Conclusions: This study highlights the importance of household transmission in carriage of OM bacteria, underscoring the need to reduce the crowding in Aboriginal households

Nasopharyngeal Carriage of Haemophilus haemolyticus in Otitis-Prone and Healthy Children▿

Haemophilus haemolyticus is often incorrectly categorized as nontypeable Haemophilus influenzae (NTHI) upon culture. PCR analyses of 266 NTHI-like nasopharyngeal isolates from children with and without recurrent acute otitis media (rAOM) revealed that 11.7% were H. haemolyticus and 9.4% gave equivocal results. Children with rAOM were more likely to carry H. haemolyticus

Geographic consistency in dominant, non-typeable Haemophilus influenzae genotypes colonising four distinct Australian paediatric groups: a cohort study

Non-typeable Haemophilus influenzae (NTHi)-associated ear and respiratory diseases (including pneumonia) represent a major health burden in many parts of the world. NTHi strains retrieved from the upper airways commonly reflect those found in the lower airways. Despite growing genomic and genotyping data on NTHi, there remains a limited understanding of global and regional NTHi population structures. The aim of this study was to determine whether nasopharyngeal carriage in four Australian paediatric groups at varying risk of NTHi colonisation was dominated by the same NTHi genotypes. Genotyping data generated by PCR-ribotyping were evaluated for 3070 NTHi isolates colonising the nasopharynges of Aboriginal and non-Aboriginal children enrolled in four longitudinal studies in three separate urban and remote regions of Australia. Several NTHi PCR-ribotypes dominated in nasopharyngeal carriage, irrespective of study setting. Principal coordinates analysis confirmed a cluster of common PCR-ribotypes among all cohorts. In conclusion, we identified dominant PCR-ribotypes common to geographically disparate Australian paediatric populations. Future genomic analyses will shed further light on the precise factors underlying the dominance of certain NTHi strains in nasopharyngeal carriage